Publications by authors named "Muxun Zhang"

35 Publications

Bilateral breast myxedema caused by Graves' disease and responsive to multipoint subcutaneous injection of long-acting glucocorticoid: Case report.

Medicine (Baltimore) 2021 Jun;100(25):e26469

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Branch of National Clinical Research Center for Metabolic Disease, Hubei.

Rationale: With the absence of ophthalmopathy, thyroid dermopathy especially lesions at atypical locations is a very rare presentation. We herein report an original case of bilateral breast myxedema caused by Grave's disease.

Patient Concerns: A 21-year-old unmarried woman presented with a 4-month history of Grave's disease and a 1-month history of progressive bilateral breast enlargement. She had symmetrical bilateral breast enlargement with redness and nonpitting thickening of the skin, diffusely enlarged thyroid glands, and no exophthalmos.

Diagnosis: Ultrasonography, magnetic resonance imaging scan, and skin biopsy confirmed the diagnosis of bilateral breast myxedema.

Interventions: The patient was treated with multipoint subcutaneous injections of triamcinolone acetonide in each breast every month.

Outcomes: The bilateral breast returned approximately to its normal size after therapy for 6 months.

Conclusions: Our case illustrates that multipoint subcutaneous injection of glucocorticoids is beneficial for bilateral breast myxedema.
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http://dx.doi.org/10.1097/MD.0000000000026469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238392PMC
June 2021

Pioglitazone ameliorates Aβ42 deposition in rats with diet-induced insulin resistance associated with AKT/GSK3β activation.

Mol Med Rep 2017 May 16;15(5):2588-2594. Epub 2017 Mar 16.

Department of Endocrinology, Tongji Hospital Affiliated to The Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Pioglitazone may have potential benefits as an alternative therapeutic treatment for patients with Alzheimer's disease (AD), particularly in individuals that also have comorbid diabetes; however, the mechanisms of action remain unclear. The present study aimed to explore the effects of pioglitazone on amyloid β, isoform 42 (Aβ42) deposition in rats with diet‑induced insulin resistance (IR). Diet‑induced IR model rats were established in the presence or absence of pioglitazone. Plasma glucose and insulin levels, and cerebrospinal fluid insulin levels were measured; in addition, hippocampal tissues were collected for immunohistochemical analysis of Aβ42 expression. The levels of insulin‑degrading enzyme (IDE) and peroxisome proliferator‑activated receptor γ (PPARγ) mRNA and protein expression were analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, the activation of glycogen synthase kinase 3β (GSK3β) induced by phosphatidylinositol 3‑kinase (PI3K) /protein kinase B (AKT) signaling was detected by western blotting. Results from the present study demonstrated that pioglitazone may enhance peripheral and brain insulin sensitivity in diet‑induced IR model rats. Treatment with pioglitazone ameliorated Aβ42 deposition in the hippocampus by increasing IDE and PPARγ expression. Notably, activation of the PI3K/AKT/GSK3β pathway was also demonstrated to serve a role in pioglitazone‑induced Aβ42 degradation, which was abrogated by the PPARγ antagonist GW9662. Results from the present study indicated that pioglitazone may improve insulin sensitivity and ameliorate Aβ42 accumulation in rats with diet‑induced IR by regulating AKT/GSK3β activation, suggesting that pioglitazone may be a promising drug for AD treatment.
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http://dx.doi.org/10.3892/mmr.2017.6342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428924PMC
May 2017

17α‑hydroxylase/17,20‑lyase deficiency in congenital adrenal hyperplasia: A case report.

Mol Med Rep 2017 Jan 12;15(1):339-344. Epub 2016 Dec 12.

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 (CYP17A1) gene located on chromosome 10q24.3, which leads to a deficiency in 17α‑hydroxylase/17,20‑lyase. The disorder is characterized by low blood levels of estrogens, androgens and cortisol, which leads to a compensatory increase in adrenocorticotropic hormone levels that stimulate the production of mineralocorticoid precursors. This subsequently leads to hypertension, hypokalemia, primary amenorrhea and sexual infantilism. Over 90 distinct genetic lesions have been identified in patients with this disorder. The prevalence of common mutation of CYP17A1 gene differs among ethnic groups. Treatment of this disorder involves replacement of glucocorticoids and sex steroids. Estrogen alone is prescribed for patients who are biologically male with 17α‑hydroxylase deficiencies that identify as female. However, genetically female patients may receive estrogen and progesterone supplementation. In the present study, a 17‑year‑old female with 17α‑hydroxylase/17,20‑lyase deficiency that presented with primary amenorrhea and sexual infantilism and no hypertension, was examined. The karyotype of the patient was 46, XX, and genetic analysis revealed the presence of a compound heterozygous mutation in exons 6 and 8, leading to the complete absence of 17α‑hydroxylase/17,20‑lyase activity. The patient was treated with prednisolone and ethinyl estradiol. In addition, a summary of the recent literature regarding CAH is presented.
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http://dx.doi.org/10.3892/mmr.2016.6029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355729PMC
January 2017

Inhibition of 11β-hydroxysteroid dehydrogenase type 1 ameliorates obesity-related insulin resistance.

Biochem Biophys Res Commun 2016 09 3;478(1):474-480. Epub 2016 Jun 3.

Division of Endocrinology, Tongji Hospital, Huazhong University of Science & Technology, Wuhan 430030, PR China. Electronic address:

Excess 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be implicated in the development of obesity related metabolic disorders. The present study measured the expression level of 11β-HSD1 in visceral adipose tissues from 23 patients undergoing abdominal operation. Correlation of 11β-HSD1 expression with BMI, waist-to-hip ratio (WHR), HOMA-IR, and serum lipids was evaluated by spearman correlation analysis. High-fat diet-induced obese (DIO) rats were orally dosed with BVT.2733 for 4 weeks. Weight, plasma insulin, and lipids were detected at the end of the treatment. The effects of 11β-HSD1 inhibition on the key insulin-signaling cascade and adipocytokines were measured by western blot and ELISA respectively. 11β-HSD1 was increased in patients with central obesity, the expression level of which was closely related with WHR (r = 0.5851), BMI (r = 0.4952), and HOMA-IR (r = 0.4637). Obesity related insulin resistance in high-fat DIO rats, as reflected by a marked decrease in IRS-1, IRS-2, GLUT4, and PI3K, could be attenuated by 11β-HSD1 inhibition. Furthermore, the down-regulation of 11β-HSD1 could correct the disordered profiles of adipocytokines including adiponectin, IL-6, and TNF-α. These findings indicated that 11β-HSD1 inhibition can give a potential benefit in reducing obesity and lowering insulin resistance by modulating the insulin-signaling pathway and adipocytokine production.
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http://dx.doi.org/10.1016/j.bbrc.2016.06.015DOI Listing
September 2016

Glargine insulin/gliclazide MR combination therapy is more effective than premixed insulin monotherapy in Chinese patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs.

Diabetes Metab Res Rev 2015 Oct 16;31(7):725-33. Epub 2015 Jun 16.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.

Background: The aim of this study is to compare the efficacy and safety of once-daily insulin glargine plus gliclazide modified release combination therapy versus twice-daily premixed insulin monotherapy in Chinese type 2 diabetic patients insufficiently controlled by oral antidiabetic agents.

Methods: In a 12-week, multicenter, randomized, parallel-group clinical trial, patients with poor glycaemic control (fasting plasma glucose ≥ 7.0 mmol/L and 7.5% < haemoglobin A1c  ≤ 10%) on oral antidiabetic drugs were randomized to the treatment groups for combination therapy (n = 52) or monotherapy (n = 53). Continuous glucose monitoring was carried out over two 72-h periods, at the beginning and the end of the study, and the data were used to calculate the 24-h mean blood glucose, mean amplitude of glycaemic excursions, standard deviation of blood glucose, and the mean of daily differences.

Results: The mean haemoglobin A1c decrease from baseline to study end was significant for both treatment groups (combination therapy: -1.23 ± 0.92%; insulin monotherapy: -1.02 ± 1.04%); moreover, the combination therapy group showed a significantly more robust haemoglobin A1c decrease (p = 0.0308). Both therapies significantly reduced the 24-h mean blood glucose (both, p < 0.001), but neither produced a significant effect on glycaemic variability, calculated as mean amplitude of glycaemic excursions, standard deviation of blood glucose, and mean of daily differences. In addition, the effects on rates of hypoglycaemic episodes were similar between the two therapies.

Conclusions: Chinese patients with type 2 diabetes inadequately controlled with oral antidiabetic agents attained greater benefit from once-daily insulin glargine plus gliclazide modified release regimen than from a twice-daily premixed insulin regimen.
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http://dx.doi.org/10.1002/dmrr.2661DOI Listing
October 2015

Clinical usefulness of lipid ratios, visceral adiposity indicators, and the triglycerides and glucose index as risk markers of insulin resistance.

Cardiovasc Diabetol 2014 Oct 20;13:146. Epub 2014 Oct 20.

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: To directly compare traditional lipid ratios (total cholesterol [TC]/high density lipoprotein cholesterol [HDL-C], non-HDL-C/HDL-C, low density lipoprotein cholesterol [LDL-C]/HDL-C, and triglycerides [TG]/HDL-C), apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio, visceral adiposity index (VAI), lipid accumulation product (LAP), and the product of TG and fasting glucose (TyG) for strength and independence as risk factors for insulin resistance (IR).

Methods: We conducted a cross-sectional analysis of 7629 Chinese adults using data from the China Health and Nutrition Survey 2009.

Results: For all lipid ratios (traditional lipid ratios and apoB/apoA-I), among both sexes, TG/HDL-C explained the most additional percentage of variation in HOMA-IR (2.9% in men, and 2.3% in women); for all variables of interest, the variability in HOMA-IR explained by VAI and TG/HDL-C were comparable; TyG had the most significant association with HOMA-IR, which explained 9.1% for men and 7.8% for women of the variability in HOMA-IR. Logistic regression analysis showed the similar patterns. Receiver operating characteristic (ROC) curve analysis showed that, among both sexes, TG/HDL-C was a better discriminator of IR than apoB/apoA-I; the area under the ROC curve (AUC) for VAI (0.695 in men and 0.682 in women) was greater than that for TG/HDL-C (AUC 0.665 in men and 0.664 in women); TyG presented the greatest value of AUC (0.709 in men and 0.711 in women).

Conclusion: The apoB/apoA-I performs no better than any of the traditional lipid ratios in correlating with IR. The TG/HDL-C, VAI and TyG are better markers for early identification of IR individuals.
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http://dx.doi.org/10.1186/s12933-014-0146-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209231PMC
October 2014

Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance.

J Clin Endocrinol Metab 2015 Jan;100(1):E96-100

Division of Endocrinology (X.C., P.L., W.H., J.Z., Y.Y., Z.L., J.X., S.S., T.D., X.S., X.Z., S.H., G.Y., M.Z., X.Y.), Department of Internal Medicine, Division of Cardiology (Le.L., D.W.), Department of Internal Medicine, Department of Ophthalmology (H.Z.), Tongji Hospital, and Department of Nutrition and Food Hygiene (Li.L.), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China.

Context: Betatrophin has recently attracted increasing interests as a potential β-cell regenerative therapy in diabetes. However, differences in betatrophin profiles in patients with type 2 diabetes mellitus (T2DM) remain unclear.

Objective: The objective of the study was to examine circulating betatrophin levels in subjects with different glucose tolerance status and its correlation with insulin resistance.

Design, Setting, And Participants: Serum betatrophin levels were measured using an ELISA in age-, sex-, body mass index-, and blood lipid-matched subjects with normal glucose tolerance (n = 137), isolated impaired fasting glucose (n = 69), isolated impaired glucose tolerance (n = 120), and newly diagnosed T2DM (n = 112) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal study.

Results: Serum betatrophin levels were elevated in patients with T2DM compared with subjects with normal glucose tolerance, isolated impaired fasting glucose, or isolated impaired glucose tolerance (798.6 ± 42.5 vs 692.7 ± 29.0, P < .05, vs 682.7 ± 43.0, P < .05, vs 646.8 ± 34.3 pg/mL, P < .01). Betatrophin levels positively correlated with the index of homeostasis model assessment of insulin resistance (partial r = 0.11); inversely correlated with quantitative insulin sensitivity check index (partial r = -0.11), the Gutt insulin sensitivity index (partial r = -0.12), and the Matsuda insulin sensitivity index (partial r = -0.11) after controlling for age, sex, body mass index, and blood lipid in all participants (all values of P < .05).

Conclusion: Circulating betatrophin levels are increased in patients with T2DM and associated with indexes of insulin resistance.
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http://dx.doi.org/10.1210/jc.2014-2300DOI Listing
January 2015

Secular trends in the prevalence of low risk factor burden for cardiovascular disease according to obesity status among Chinese adults, 1993-2009.

BMC Public Health 2014 Sep 16;14:961. Epub 2014 Sep 16.

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095#, Jiefang Road, Wuhan 430030, China.

Background: Cardiovascular disease (CVD) and obesity are now common among Chinese. We aimed to examine secular trends in the prevalence of low risk profile and to examine whether comparable changes in the prevalence of low risk profile across waist circumference (WC) groups and body mass index (BMI) categories have occurred.

Methods: We used data from the nationwide China Health and Nutrition Survey conducted in 1993, 1997, 2000, 2004, 2006, and 2009. There were 7274, 8368, 9369, 8948, 8786, and 9278 participants included in the analyses across the six study periods. We created an index of low risk factor burden from the following variables: not currently smoking, BMI < 25 kg/m2, WC < 90/80 cm in men/women, untreated systolic/diastolic blood pressure < 120/80 mmHg, and not having been previously diagnosed with diabetes.

Results: During the period of 1993-2009, the age-adjusted prevalence of low risk profile decreased from 16.2 to 11.5% among men and from 46.3 to 34.6% among women (both P < 0.001); Similar significant trends were observed in all age groups, rural/urban settings, education groups, WC status and BMI categories. The change in the prevalence of low risk profile was more striking among obese persons (P for interaction terms cohort *BMI were < 0.001). In 2009, 2.0 and 25.6% among central obese men and women had a low risk profile; Of note, was that 0.1 and 0.3% general obese men and women had a low risk profile.

Conclusions: The prevalence of low risk profile declined considerably over the past 17 years in all demographic groups, WC status, and BMI categories. Public health prevention strategies are urgently needed.
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http://dx.doi.org/10.1186/1471-2458-14-961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189202PMC
September 2014

The changes of leukocyte telomere length and telomerase activity after sitagliptin intervention in newly diagnosed type 2 diabetes.

Diabetes Metab Res Rev 2015 Mar 2;31(3):256-61. Epub 2014 Sep 2.

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: In recent years, increasing evidence suggests a potential importance of telomere biology in type 2 diabetes. The aim of this study was to determine whether sitagliptin, a medicine generally used in diabetes, can influence the telomere and telomerase in newly diagnosed type 2 diabetic patients.

Methods: Type 2 diabetic patients (T2D, n = 38) and non-diabetic subjects (control, n = 31) were randomly selected from the outpatient of Tongji Hospital, Tongji Medical College, Huazhong university of Science and Technology. Leukocyte telomere length ratio was measured using a quantitative polymerase chain reaction and was analysed. Telomerase activity was measured by polymerase chain reaction enzyme-linked immunosorbent assay method. Peripheral insulin resistance (homeostasis model assessment) was calculated from fasting plasma glucose and fasting plasma insulin.

Results: Telomere length of the type 2 diabetic patients (1.58 ± 0.57) was significantly shorter than those of control subjects (3.98 ± 0.90) and was significantly elongated after intervention by sitagliptin. There was no significant difference between the T2D and control group in telomerase activity, and the treatment of sitagliptin in T2D group showed no significant effect on the telomerase activity.

Conclusions: In type 2 diabetes patients, leukocyte telomere length is significantly reduced, whereas the telomerase activity seems less influenced. Sitagliptin might protect β-cells in the pancreas by elongating the telomere length.
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http://dx.doi.org/10.1002/dmrr.2578DOI Listing
March 2015

Influence of vitamin E supplementation on glycaemic control: a meta-analysis of randomised controlled trials.

PLoS One 2014 16;9(4):e95008. Epub 2014 Apr 16.

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Observational studies have revealed that higher serum vitamin E concentrations and increased vitamin E intake and vitamin E supplementation are associated with beneficial effects on glycaemic control in type 2 diabetes mellitus (T2DM). However, whether vitamin E supplementation exerts a definitive effect on glycaemic control remains unclear. This article involves a meta-analysis of randomised controlled trials of vitamin E to better characterise its impact on HbA1c, fasting glucose and fasting insulin. PubMed, EMBASE and the Cochrane Library were electronically searched from the earliest possible date through April 2013 for all relevant studies. Weighted mean difference (WMD) was calculated for net changes using fixed-effects or random-effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. Fourteen randomised controlled trials involving individual data on 714 subjects were collected in this meta-analysis. Increased vitamin E supplementation did not result in significant benefits in glycaemic control as measured by reductions in HbA1c, fasting glucose and fasting insulin. Subgroup analyses revealed a significant reduction in HbA1c (-0.58%, 95% CI -0.83 to -0.34) and fasting insulin (-9.0 pmol/l, 95% CI -15.90 to -2.10) compared with controls in patients with low baseline vitamin E status. Subgroup analyses also demonstrated that the outcomes may have been influenced by the vitamin E dosage, study duration, ethnic group, serum HbA1c concentration, and fasting glucose control status. In conclusion, there is currently insufficient evidence to support a potential beneficial effect of vitamin E supplementation on improvements of HbA1c and fasting glucose and insulin concentrations in subjects with T2DM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095008PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989270PMC
February 2015

Protective action of liraglutide in beta cells under lipotoxic stress via PI3K/Akt/FoxO1 pathway.

J Cell Biochem 2014 Jun;115(6):1166-75

Division of Endocrinology, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, 430030, P.R. China.

Liraglutide, a modified form of glucagon-like peptide-1 (GLP-1), has been found to improve beta cell function in type 2 diabetes (T2DM). However, the effect of liraglutide on beta cell function under lipotoxic stress and the underlying molecular mechanisms remain unclear. In the present study, we investigated the role of PI3K/Akt/FoxO1 signaling in liraglutide-involved beta cell protection in high free fatty acids (FFAs) condition. The apoptosis, proliferation, and insulin secretion capability of MIN6 cells and islets from C57BL/6J mice were evaluated when exposed to FFAs with/without liraglutide. The expression of effectors involved in PI3K/Akt/FoxO1signalling pathway was detected by real-time PCR and western blotting in MIN6 cells and islets from C57BL/6J mice. Liraglutide substantially inhibited the lipoapoptosis and improved the proliferation and insulin secretion of beta cells in high FFAs condition. Western blot revealed that the phosphorylation of Akt and FoxO1 was markedly decreased under lipid stress but was elevated when treated with liraglutide. Moreover, FFAs could up-regulate the expression levels of p27, Bax, Cidea but down-regulate the expression levels of Pdx-1, MafA, and NeuroD in beta cells, which was canceled by the addition of liraglutide. Moreover, LY294002, a PI3K inhibitor, could significantly abrogate all the protective actions of liraglutide against lipotoxicity. We concluded that liraglutide markedly improved beta cell function under lipid stress and that the protective action of liraglutide was mediated by activation of PI3K/Akt, which resulted in inactivation of FoxO1 along with the down-regulation of p27, Bax, Cidea and up-regulation of Pdx-1, MafA, and NeuroD expressions.
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http://dx.doi.org/10.1002/jcb.24763DOI Listing
June 2014

Subcutaneous administration of liraglutide ameliorates Alzheimer-associated tau hyperphosphorylation in rats with type 2 diabetes.

J Alzheimers Dis 2013 ;37(3):637-48

Department of Endocrinology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Background/objective: Type 2 diabetes increases the risk for developing Alzheimer's disease (AD), a progressive neurodegenerative disorder. Brain insulin resistance contributes to the pathogenesis of AD, and abnormal hyperphosphorylation of tau protein is crucial to neurodegeneration. Here we studied whether liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) and a new anti-diabetic drug, can promote brain insulin signaling and inhibit tau hyperphosphorylation in the brains of type 2 diabetic rats.

Methods: Type 2 diabetic rats were treated with subcutaneous administration of liraglutide (0.2 mg/kg body weight) or, as a control, saline twice a day for up to four weeks. Blood, cerebrospinal fluid (CSF), and brain tissue (n = 7 each group) were collected for analyses after liraglutide or saline administration for one, two, three, and four weeks.

Results: We found decreased CSF insulin, hyperphosphorylation of tau at AD-relevant phosphorylation sites, and decreased phosphorylation of protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β) in the brain, which indicated decreased insulin signaling leading to overactivation of GSK-3β, a major tau kinase, in type 2 diabetic rats. Liraglutide treatment not only ameliorated hyperglycemia and peripheral insulin resistance, but also reversed these brain abnormalities in a time-dependent manner.

Conclusion: Our results indicated that subcutaneous administration of liraglutide restores both peripheral and brain insulin sensitivity and ameliorates tau hyperphosphorylation in rats with type 2 diabetes. These findings support the potential use of liraglutide for the prevention and treatment of AD in individuals with type 2 diabetes.
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http://dx.doi.org/10.3233/JAD-130491DOI Listing
June 2014

Neutralization of interleukin-17 attenuates high fat diet-induced non-alcoholic fatty liver disease in mice.

Acta Biochim Biophys Sin (Shanghai) 2013 Sep 19;45(9):726-33. Epub 2013 Jun 19.

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Non-alcoholic fatty liver disease (NAFLD) is hepatic manifestation of a metabolic syndrome and includes a spectrum of hepatic steatosis, steatohepatitis, and fibrosis. Interleukin-17 (IL-17) has been reported to play a critical role in inflammatory progression of some liver diseases. The present study was designed to investigate the role of IL-17 on high fat diet-induced NAFLD in C57BL/6 mice. IL-17 blockade with anti-IL-17mAb significantly improved liver function, attenuated hepatic lipid accumulation, suppressed Kuffer cells activation, and decreased pro-inflammatory cytokines levels, which were associated with inhibition of NF-κB signaling cascades activation. Our data suggested that IL-17 was related to disease progression in NAFLD mouse model and blocking IL-17 may be a promising novel therapeutic approach for patients with NAFLD.
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http://dx.doi.org/10.1093/abbs/gmt065DOI Listing
September 2013

Signaling molecules involved in lipid-induced pancreatic beta-cell dysfunction.

DNA Cell Biol 2013 Feb;32(2):41-9

Division of Endocrinology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, People's Republic of China.

The increasing incidence of type 2 diabetes mellitus is partially due to the rising obesity rates and the elevated levels of free fatty acids (FFAs). It is known that FFAs are putative mediators of beta-cell dysfunction, which is characterized with impaired glucose-stimulated insulin secretion and increased apoptosis, being defined as lipotoxicity. To date, many factors and their related signal pathways have been reported to be involved in FFA-induced beta-cell dysfunction. However, the entire blueprint is still not obtained. Some essential and newfound effectors, including the sterol regulatory element-binding protein (SREBP)-1c, farnesoid X receptor (FXR), forkhead box-containing protein O (FoxO) 1, ubiquitin C-terminal hydrolase L (UCHL) 1, N-myc downstream-regulated gene (NDRG) 2, perilipin family proteins, silent information regulator 2 protein 1 (Sirt1), pituitary adenylate cyclase-activating polypeptide (PACAP), and ghrelin are described in this review, which may help to further understand the molecular network for lipotoxicity.
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http://dx.doi.org/10.1089/dna.2012.1874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557433PMC
February 2013

Wnt3a regulates proliferation, apoptosis and function of pancreatic NIT-1 beta cells via activation of IRS2/PI3K signaling.

J Cell Biochem 2013 Jul;114(7):1488-97

Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Wnt-signaling pathway is implicated in pancreatic development and functional regulation of mature beta-cells. Wnt3a/Wnt pathway activation expands islet cell mass in vitro by increasing proliferation and decreasing apoptosis of beta-cells, thereby enhancing its function. However, the signaling pathways that mediate these effects remain unknown. By using a clonal beta-cell line (NIT-1), we examined the role of IRS2/PI3K in the mediation of Wnt3a-stimulated beta-cell growth. Real-time PCR and Western blot were employed to investigate the activity of Wnt/β-catenin and IRS2/PI3K signaling. Proliferation of NIT-1 cells was assessed by BrdU incorporation, and apoptosis was quantitatively determined by TUNEL and flow cytometry (FCM). Dkk1, an inhibitor of Wnt signaling, and wortmannin, an inhibitor of PI3K, were also used. Results showed that Wnt3a rapidly activated Wnt/β-catenin signaling, promoted IRS2 expression and Akt phosphorylation in NIT-1 cells. These effects were completely abrogated by Dkk1 or partially eliminated by wortmannin. Wnt3a also promoted NIT-1 cell proliferation, inhibited cytokine-induced beta-cell apoptosis, and increased insulin secretion. Both of these effects were also eliminated by Dkk1 or wortmannin. Our results demonstrated that Wnt3a regulates proliferation, apoptosis and enhances function of pancreatic NIT-1 beta cells via activation of Wnt/β-catenin signaling, involving crosstalk with IRS2/PI3K signaling, with the effect of Wnt signaling on beta-cells also being IRS2/PI3K/AKT dependent.
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http://dx.doi.org/10.1002/jcb.24490DOI Listing
July 2013

Th17 cells in type 1 diabetes.

Cell Immunol 2012 Nov 28;280(1):16-21. Epub 2012 Nov 28.

Division of Endocrinology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, PR China.

T1D is an autoimmune disorder, which involves the CD4(+) as well as CD8(+) T-cell-mediated destruction of β cells. Recently, another population of T cells (Th17) is found to be involved in T1D pathology. This review will discuss the characteristics of Th17 cells and the mechanism of Th17-mediated T1D development. Th17 cell expansion is unstrained under T1D condition. Certain Treg cells are defective in T1D and lose the control of Th17 expansion. In addition, the altered function of APCs and a subset of monocytes which spontaneously secrete IL-1β and IL-6 in T1D determine the abnormal expansion of Th17 as well. The pathogenic Th17 cells can cause the imbalance between Teff and Treg cells. Conversion from Th17 to Th1 phenotype and Th17 stimulated CTL responses may play an accessory role in T1D as well. Due to the effects of Th17 on T1D, therapeutic strategies designed to inhibit these cells are applicable and the positive effects are obvious. Taken together, Th17 may exert essential effects on the development of T1D. Identification of the underlying mechanism may inspire new viewpoints for the therapy of this disease.
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http://dx.doi.org/10.1016/j.cellimm.2012.11.001DOI Listing
November 2012

Role of stereotaxically injected IgG from db/db mice in the phosphorylation of the microtubule-associated protein tau in hippocampus.

Brain Res 2012 Nov 1;1486:14-26. Epub 2012 Oct 1.

Department of Endocrinology, XiangYang Central Hospital, XiangYang, China.

People with type 2 diabetes (T2DM) mellitus are high risk for dementia and Alzheimer's disease (AD) via several plausible pathways. However, the underlying mechanisms have been still unclear, and the relation of immune injury to the pathogenesis of T2DM-related AD is not yet completely understood. Our present study aimed to elucidate the possible role of immunoglobulin IgG in the immune process of AD associated with T2DM in db/db mice. Hippocampi of 20 db/db mice and 20 C57BL/6 mice were subjected to immunohistochemistry and immunofluorescence assays. The phosphorylation of tau, glycogen synthase kinase (GSK)-3β and AKT activity was examined by Western blot analysis. IgG purified from the sera of IgG deposit-positive db/db mice was stereotaxically injected into the hippocampi of another 12 db/db mice and 12 C57BL/6 mice. The phosphorylation of tau, Abeta, GSK-3β and AKT activity was analyzed. Compared with the C57BL/6 control, 13 of the 20 db/db mice exhibited high levels of IgG deposits in the hippocampus. Treatment with IgG triggered tau hyperphosphorylations and Abeta deposition, which are likely major factors in AD. Meanwhile, IgG inhibited AKT phosphorylation and promoted GSK-3β activity. The IgG deposits observed in some db/db mice were possibly related to the impairment of T2DM-related AD development. Some autoimmune processes may be involved in AD in type 2 diabetes mellitus development at the level of the hippocampus.
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http://dx.doi.org/10.1016/j.brainres.2012.08.049DOI Listing
November 2012

Intranasal insulin ameliorates tau hyperphosphorylation in a rat model of type 2 diabetes.

J Alzheimers Dis 2013 ;33(2):329-38

Department of Endocrinology, Tongji Hospital, Tongji Medical College of the Huazhong University of Science and Technology, Wuhan, PR China.

Recent studies have demonstrated that insulin plays important roles in the brain, including regulation of glucose metabolism and modulation of learning and memory. We have found dysregulation of brain insulin signaling in both Alzheimer's disease (AD) and type 2 diabetes (T2D), which correlates to hyperphosphorylation of tau, a key abnormal tau modification leading to neurofibrillary tangles. Here, we investigated tau phosphorylation and the two key components of the insulin signaling pathway, protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β), in a rat model of T2D produced by a high protein, high glucose, and high fat diet followed by intraperitoneal injection of streptozocin. We found tau hyperphosphorylation, decreased AKT activation, and GSK-3β over-activation in T2D rat brains. Intranasal insulin treatment for four weeks normalized AKT and GSK-3β, as well as reduced tau hyperphosphorylation in T2D rat brains, whereas four-week treatments with subcutaneous insulin had minimal effects on brain GSK-3β and tau phosphorylation. These results suggest decreased brain insulin signaling and tau hyperphosphorylation in the rat model of T2D and demonstrate the efficacy of intranasal insulin treatment to reverse these brain abnormalities. Our findings provide further mechanism by which T2D increases the risk for AD and also support the potential use of intranasal insulin for the treatment of AD.
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http://dx.doi.org/10.3233/JAD-2012-121294DOI Listing
May 2013

Plasma heme oxygenase-1 concentration in relation to impaired glucose regulation in a non-diabetic Chinese population.

PLoS One 2012 12;7(3):e32223. Epub 2012 Mar 12.

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Background: Our previous study has recently shown that plasma heme oxygenase-1 (HO-1), a stress-responsive protein, is elevated in individuals with type 2 diabetes. The current study aimed to examine the association between plasma HO-1 concentration and impaired glucose regulation (IGR) in non-diabetic individuals.

Methods: We conducted a case-control study including a total of 865 subjects (262 IGR individuals and 603 healthy controls) in a Chinese population. Basic characteristics were collected by questionnaire and standardized anthropometric measurements. Plasma HO-1 concentration was determined by ELISA.

Results: Plasma HO-1 concentration was significantly increased in IGR individuals compared with healthy controls (1.34 (0.81-2.29) ng/ml vs 0.98 (0.56-1.55) ng/ml, P<0.001). After adjustment for age, sex, and BMI, the ORs for IGR in the highest quartile of plasma HO-1 concentrations, compared with the lowest, was 3.42 (95% CI 2.11-5.54; P for trend <0.001). The trend remained significant even after additional adjustment for smoking, alcohol drinking, hypertension, family history of diabetes, lipid profiles and C-reactive protein. In the receiver-operating characteristic curve analysis, addition of plasma HO-1 concentration to a model with known risk factors yielded significantly improved discriminative value for IGR (area under the curves 0.75 (95% CI 0.71-0.78) vs. 0.72 (95% CI 0.69-0.76); P for difference = 0.026).

Conclusions: Elevated plasma HO-1 concentration is significantly associated with increased ORs for IGR. However, its clinical utility should be validated in further studies, especially in prospective cohort studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0032223PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299661PMC
August 2012

Erythropoietin protects pancreatic β-cell line NIT-1 cells against cytokine-induced apoptosis via phosphatidylinositol 3-kinase/Akt signaling.

Endocr Res 2011 ;36(1):25-34

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.

Objective: Erythropoietin (EPO) is a cytokine that regulates the proliferation, differentiation, and survival of erythroid progenitor cells. EPO has recently been demonstrated to have a tissue-protective role by mediating anti-apoptotic signals through the erythropoietin receptor (EPOR) in various tissues, including brain, liver, and heart. We have previously examined pancreatic β-cell line NIT-1 cells for the expression of EPOR by real-time PCR and determined that these cells were protected by EPO against cytokine-induced apoptosis. The precise underlying anti-apoptotic mechanisms in pancreatic β-cells are poorly understood. The purpose of this study is to examine erythropoietin receptor expression in the NIT-1 pancreatic beta-cell line and the intracellular pathway related with its anti-apoptosis effect in NIT-1 cells.

Methods: we examined the expression of EPOR by western blot. We investigate the role of erythropoietin in the survival of these cells, and whether the PI3K/AKT pathway is involved in this protective process.

Results: NIT-1 cells expressed EPOR and, in the presence of certain cytokines, exposure of NIT-1 cells to recombinant human erythropoietin (rhEPO) significantly improved the impaired insulin secretion and inhibited cytokine-induced apoptosis. RhEPO caused a rapid activation of Akt and increased expression of Bcl-2. The protective anti-apoptotic effect of rhEPO was significantly abolished by a specific phosphatidylinositol 3-kiniase (PI3K) inhibitor, LY294002.

Conclusions: Our findings indicate that EPOR is expressed in pancreatic β-cell line NIT-1 cells and suggest that EPO may act as a survival factor requiring the PI3K/Akt pathway.
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http://dx.doi.org/10.3109/07435800.2010.534753DOI Listing
April 2011

The therapeutic role of very low-density lipoprotein receptor gene in hyperlipidemia in type 2 diabetic rats.

Hum Gene Ther 2011 Mar 2;22(3):302-12. Epub 2011 Feb 2.

Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.

Hyperlipidemia is a common feature of type 2 diabetes and is related to cardiovascular disease. The very low-density lipoprotein receptor (VLDLR) binds to and internalizes triglyceride-rich lipoproteins with high specificity. In this study, we evaluated the role of VLDLR in hyperlipidemia in type 2 diabetic rats. Type 2 diabetes was induced in male Wistar rats by injection of low-dose streptozotocin coupled with a high-fat diet. Recombinant adeno-associated viral (rAAV) vectors encoding the human VLDLR gene (rAAV·VLDLR) were intravenously administered to diabetic rats. Results showed that in vivo, total VLDLR mRNA and protein levels were significantly decreased in skeletal muscle (type I VLDLR mainly reduced) and adipose tissue (type II VLDLR mainly reduced) but not in heart in hypercholesterolemic, hypertriglyceridemic diabetic rats compared with normal rats. And in vitro, in 3T3-L1 adipocytes, insulin-induced (1.0 mmol/liter) insulin resistance significantly decreased VLDLR mRNA expression. In rats, rAAV·VLDLR delivery resulted in a reduction in serum cholesterol and triglyceride that lasted for the duration of the study (12 weeks). Fasting blood insulin was significantly lower in the rAAV·VLDLR group versus untreated diabetic rats although fasting blood glucose levels were not significantly different in both groups at the end of the study. rAAV·VLDLR-treated animals had significantly increased lipoprotein lipase activity and reduced aortic atherosclerosis. Taken together, our data suggest that type 2 diabetes and related insulin resistance manifest decreased VLDLR with elevated serum cholesterol and triglyceride levels, and overexpression of VLDLR through a single injection of rAAV·VLDLR reversed these effects and consequentially attenuated aorta atherosclerotic plaque progression.
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http://dx.doi.org/10.1089/hum.2010.038DOI Listing
March 2011

Plasma heme oxygenase-1 concentration is elevated in individuals with type 2 diabetes mellitus.

PLoS One 2010 Aug 25;5(8):e12371. Epub 2010 Aug 25.

Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Background: Circulating concentrations of heme oxygenase-1 (HO-1) have been recently reported to be elevated in several chronic disorders. However, no study has ever examined the association between circulating HO-1 concentrations and type 2 diabetes mellitus (T2DM).

Methods And Findings: 581 cases with newly-diagnosed T2DM (New-T2DM) and 611 comparison controls were recruited in this two-phase case-control study, comprising 420 cases and 429 controls collected in the first phase study and 161 cases and 182 controls in the second phase replication study. Analyses, using both separated data and combined data from the two-phase studies, show that plasma HO-1 concentrations were significantly increased in New-T2DM cases compared to controls (P<0.001). Plasma HO-1 concentrations were significantly correlated with plasma glucose concentrations, HOMA-beta and HOMA-IR (P<0.001). After adjustment for age, sex, BMI and family history of diabetes, the ORs for New-T2DM in the highest quartile of plasma HO-1 concentrations, compared with the lowest, was 8.23 (95% CI 5.55-12.21; P for trend <0.001). The trend remained significant after additional adjustment for fasting plasma glucose/insulin, HOMA-beta/HOMA-IR, TC/TG, smoking, drinking and history of hypertension, and even in further stratification analysis by age, sex, BMI, smoking, drinking and history of hypertension.

Conclusions: Elevated plasma HO-1 concentrations are associated with higher ORs for New-T2DM, which add more knowledge regarding the important role of oxidative stress in T2DM. More consequent studies were warranted to confirm the clinical utility of plasma HO-1, especially in diagnosis and prognosis of T2DM and its complications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012371PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928270PMC
August 2010

SREBP-1c, Pdx-1, and GLP-1R involved in palmitate-EPA regulated glucose-stimulated insulin secretion in INS-1 cells.

J Cell Biochem 2010 Oct;111(3):634-42

Division of Endocrinology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430030, PR China.

Impairment of glucose-stimulated insulin secretion (GSIS) caused by glucolipotoxicity is an essential feature in type 2 diabetes mellitus (T2DM). Palmitate and eicosapentaenoate (EPA), because of their lipotoxicity and protection effect, were found to impair or restore the GSIS in beta cells. Furthermore, palmitate was found to up-regulate the expression level of sterol regulatory element-binding protein (SREBP)-1c and down-regulate the levels of pancreatic and duodenal homeobox (Pdx)-1 and glucagon-like peptide (GLP)-1 receptor (GLP-1R) in INS-1 cells. To investigate the underlying mechanism, the lentiviral system was used to knock-down or over-express SREBP-1c and Pdx-1, respectively. It was found that palmitate failed to suppress the expression of Pdx-1 and GLP-1R in SREBP-1c-deficient INS-1 cells. Moreover, down-regulation of Pdx-1 could cause the low expression of GLP-1R with/without palmitate treatment. Additionally, either SREBP-1c down-regulation or Pdx-1 over-expression could partially alleviate palmitate-induced GSIS impairment. These results suggested that sequent SREBP-1c-Pdx-1-GLP-1R signal pathway was involved in the palmitate-caused GSIS impairment in beta cells.
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http://dx.doi.org/10.1002/jcb.22750DOI Listing
October 2010

A genetic variation in the fat mass- and obesity-associated gene is associated with obesity and newly diagnosed type 2 diabetes in a Chinese population.

Diabetes Metab Res Rev 2010 Feb;26(2):128-32

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, PR China.

Background: Recently, a genome-wide association study identified a strong association between the fat mass- and obesity-associated rs9939609 single nucleotide polymorphism (SNP) and the risk of obesity in European population. However, the results in Chinese population were reported to be contradictory. Therefore, our aim was to examine whether this SNP is associated with obesity and newly diagnosed type 2 diabetes (T2D) in Chinese population.

Methods: We genotyped rs9939609 in 2587 subjects [obesity 243, overweight 976, normal weight 1368 or newly diagnosed T2D 877, impaired glucose regulation 305, normal glucose tolerance (NGT) 1405] using an allelic discrimination assay-by-design TaqMan method on ABI7900HT. We analysed associations of the rs9939609 SNP with obesity and newly diagnosed T2D through Logistic regression analysis.

Results: In obesity case-control study, we found that the A allele was strongly associated with obesity and overweight. The odds ratios for the allele A versus T were 1.447 for Obesity versus normal weight (95% CI 1.104-1.896, p = 0.007) and 1.363 for Overweight versus normal weight (95% CI 1.149-1.617, p < 0.0001). In T2D case-control study, the odds ratios for the allele A versus T were 1.305 for T2D versus NGT (95% CI 1.097-1.552, p = 0.003) and 1.280 for combined T2D and impaired glucose regulation (IGR) versus NGT (95% CI 1.089-1.503, p = 0.003). The associations of the A allele with T2D and combined T2D and IGR remained significant with adjustment for age, sex and body mass index (BMI).

Conclusion: The fat mass- and obesity-associated gene rs9939609 SNP is strongly associated with risk of obesity and newly diagnosed T2D in the Chinese population.
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http://dx.doi.org/10.1002/dmrr.1066DOI Listing
February 2010

Association between heme oxygenase-1 gene promoter polymorphisms and type 2 diabetes in a Chinese population.

Am J Epidemiol 2009 Sep 20;170(6):747-56. Epub 2009 Aug 20.

Department of Nutrition and Food Hygiene and MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

The authors aimed to determine whether 2 functional polymorphisms in the heme oxygenase-1 (HO-1) gene promoter are associated with type 2 diabetes mellitus (T2DM). A Chinese case-control study involving 1,103 newly diagnosed T2DM patients, 371 patients with impaired glucose regulation (IGR), and 1,615 controls was performed (December 2004-December 2007). A (GT)(n) microsatellite polymorphism and a single nucleotide polymorphism, T(-413)A, were genotyped, and their functional relevance was evaluated by examining the level of HO-1 protein expression. For the (GT)(n) microsatellite polymorphism, genotypes with the L (GT)(n) allele (>or=25 GT repeats) were associated with increased odds of IGR or T2DM compared with the S/S genotype (<25 GT repeats) (S/L genotype: odds ratio (OR) = 1.35, P = 0.048; L/L genotype: OR = 1.65, P = 0.006). Subsequent haplotype analysis showed that haplotype TL contributed to increased odds of IGR or T2DM compared with haplotype TS (OR = 1.56, P = 0.003). In functional analyses, HO-1 expression level was significantly reduced in persons with IGR and T2DM carrying the L/L (GT)(n) genotype compared with persons with the S/S genotype. Further haplotype combination assay confirmed the functional dominance of the (GT)(n) microsatellite polymorphism over the T(-413)A single nucleotide polymorphism. These results support an association between the HO-1 (GT)(n) microsatellite polymorphism, HO-1 expression levels, and the odds of T2DM.
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http://dx.doi.org/10.1093/aje/kwp196DOI Listing
September 2009

Effects of high concentration glucose on the expression of NF-kappaB, Bax and cytochrome C and apoptosis of islet cells in mice.

J Huazhong Univ Sci Technolog Med Sci 2009 Aug 7;29(4):439-44. Epub 2009 Aug 7.

Department of Diabetes Research Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530007, China.

The roles of NF-kappaB (NF-kappaB) expression, Bax activity and cytochrome C (Cyt C) release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were isolated from Kunming mice, were cultured with different concentrations of glucose in DMEM, and divided into the following groups: G1, G2, G3, G4, G5, and G6 groups, corresponding to the glucose concentrations of 5.6, 7.8, 11.1, 16.7, 22.5, and 27.6 mmol/L, respectively. After culture for 120 h, insulin secretion was evaluated by radioimmunoassay, and the NF-kappaB expression was detected by immunocytochemistry. Bax activity and Cyt C release were measured by immunofluorescence, and apoptosis was examined by Hoechst33342 assay. The results showed that in G1, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-kappaB expression was also increased (P<0.05), but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them. However, in G4, G5, and G6 groups, apoptosis rate of islet cells, NF-kappaB expression, Bax activity, and Cyt C release were all significantly increased, and insulin secretion was impaired as compared with G1, G2, and G3 groups (P<0.05). It was concluded that the exposure of islet cells to high glucose could induce islet cells apoptosis as well as impaired insulin secretion. The NF-kappaB signaling pathway and mitochondria pathway in islet cells might play some roles in the progressive loss of islet cells in diabetes. The inhibition of the NF-kappaB expression could be an effective strategy for protecting pancreatic islet cells.
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http://dx.doi.org/10.1007/s11596-009-0410-zDOI Listing
August 2009

Transcription factors involved in glucose-stimulated insulin secretion of pancreatic beta cells.

Biochem Biophys Res Commun 2009 Jul 3;384(4):401-4. Epub 2009 May 3.

Division of Endocrinology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, Hubei Province, PR China.

GSIS, the most important function of pancreatic beta cell, is essential for maintaining the glucose homeostasis. Transcription factors are known to control different biological processes such as differentiation, proliferation and apoptosis. In pancreas, some transcription factors are involved in regulating the function of beta cells. In this review, the role of these transcription factors including Pdx-1, FoxO1, SREBP-1c, and MafA in GSIS is highlighted. The related molecular mechanisms are analyzed as well. Furthermore, the association between the role of transcription factors in GSIS and the development of T2DM is discussed.
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http://dx.doi.org/10.1016/j.bbrc.2009.04.135DOI Listing
July 2009

Association between C-reactive protein and pre-diabetic status in a Chinese Han clinical population.

Diabetes Metab Res Rev 2009 Mar;25(3):219-23

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, PR China.

Background: C-reactive protein (CRP) has been showed to be associated with type 2 diabetes mellitus, but whether CRP underlies glucose disorders in Asian people is still unclear, for they have much lower body mass index (BMI) levels than these Westerns in previous studies.

Method: In this clinical-based cross-sectional study, the association between CRP and hyperglycaemia in different BMI levels and different gender was compared among 1730 Chinese Han men and women, including 1258 subjects with normal glucose tolerance (NGT), 126 subjects with impaired fasting glucose (IFG) and 346 subjects with impaired glucose tolerance (IGT). Subjects with isolated IFG or IGT were all newly diagnosed and did not use anti-diabetic drugs.

Results: Compared with subjects with NGT, BMI, fasting blood glucose, homoeostasis model assessment insulin resistance (HOMA-IR), blood pressure, dyslipidemia, and serum CRP levels were increased in subjects with IGT and IFG. In stratified analyses, increasing CRP levels were strongly associated with prevalence of IGT and IFG in different BMI strata. After adjustment for sex, age, BMI, education, alcohol consumption, smoking, hypertension status, recreational physical activity and occupational physical activity, the ORs across quartiles of CRP were 1.00, 1.43, 2.14 and 2.29 for IFG (P for trend: 0.025) and 1.00, 1.85, 2.32 and 2.79 for IGT (P for trend: 0.012).

Conclusion: These results support the hypothesis that chronic inflammation may be involved in the development of hyperglycaemia, even though in a thinner and healthy population.
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http://dx.doi.org/10.1002/dmrr.923DOI Listing
March 2009

Expression of EPO receptor in pancreatic cells and its effect on cell apoptosis.

J Huazhong Univ Sci Technolog Med Sci 2008 Feb;28(1):49-51

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

In order to explore the expression of erythropoietin receptor (EPOR) in pancreatic cell line NIT-1 and its effect on cell apoptosis after binding with erythropoietin (EPO), NIT-1 cells were cultured and expanded. The expression of EPOR was detected using electrophoresis. NIT-1 apoptosis was induced by cytokines and their effects on cell apoptosis and cell insulin secretion were assayed after binding of EPO to EPOR. The results showed that EPOR was expressed in NIT-1 cells. Recombinant human EPO (rHuEPO) had no effect on cell apoptosis but significantly inhibited apoptosis induced by cytokines. rHuEPO had no effect on cell insulin secretion but significantly improved insulin secretion inhibited by cytokines. From these findings, it was concluded that EPOR was expressed in NIT-1 cells and EPO could protect NIT-1 cells from apoptosis induced by cytokines.
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http://dx.doi.org/10.1007/s11596-008-0112-yDOI Listing
February 2008

Increased acylation-stimulating protein, C-reactive protein, and lipid levels in young women with polycystic ovary syndrome.

Fertil Steril 2009 Jan 18;91(1):213-9. Epub 2008 Jan 18.

Department of Endocrinology, Tongji Hospital, Hua Zhong University of Science and Technology, Wuhan, Hubei, China.

Objective: To evaluate potential changes that are independent of body size in the lipogenic adipokine acylation-stimulating protein (ASP), complement C3 (ASP precursor), and C-reactive protein (CRP) in subjects with polycystic ovary syndrome (PCOS).

Design: Cross-sectional analysis.

Setting: Endocrine clinic in China.

Patient(s): Thirty-four women with PCOS and 41 age- and body mass index (BMI)-matched controls were recruited.

Intervention(s): Fasting blood samples were collected.

Main Outcome Measure(s): Plasma glucose, insulin, lipids, ASP, C3, CRP, and homeostasis model assessment of insulin resistance were measured.

Result(s): Plasma ASP, CRP, insulin, cholesterol, and nonesterified fatty acids were increased significantly in women with PCOS compared with in controls. Although each of these parameters also was statistically significantly correlated directly with BMI, the association with PCOS status was independent of BMI, with increased plasma values at all levels of BMI. In control subjects, CRP and C3 correlated with glucose and triglyceride, only CRP correlated with nonesterified fatty acids and cholesterol, and ASP correlated with triglyceride (again, all correlations were significant), whereas in subjects with PCOS, several of these correlations were lost, as a result of consistently higher levels of CRP and ASP regardless of BMI.

Conclusion(s): Levels of ASP, CRP, and lipids are increased in subjects with PCOS, regardless of the level of BMI. The increased ASP level in both PCOS groups suggests that the ASP metabolism may be altered.
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http://dx.doi.org/10.1016/j.fertnstert.2007.11.031DOI Listing
January 2009
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