16,231 results match your criteria Diabetes[Journal]


Impaired Glucocorticoid Suppression of TGFβ Signaling in Human Omental Adipose Tissues Limits Adipogenesis and May Promote Fibrosis.

Diabetes 2018 Dec 7. Epub 2018 Dec 7.

Diabetes Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Visceral obesity is associated with insulin resistance and higher risk of type 2 diabetes and metabolic diseases. A limited ability of adipose tissues to remodel through the recruitment and differentiation of adipose stem cells (ASCs) is associated with adipose tissue inflammation and fibrosis and the metabolic syndrome. We show that the lower adipogenesis of omental (Om) compared to abdominal subcutaneous (Abdsc) ASCs was associated with higher secretion of TGFβ ligands that acted in an autocrine/paracrine loop to activate SMAD2 and suppress adipogenesis. Read More

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December 2018

Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1.

Diabetes 2018 Nov 28. Epub 2018 Nov 28.

Department of Nutrition and Food Science, College of Agriculture and Life Sciences, Texas A&M University, College Station, TX 77843, United States

Premenopausal women exhibit enhanced insulin sensitivity and reduced incidence of type 2 diabetes mellitus (T2D) compared with age-matched men, but this advantage disappears after menopause with disrupted glucose homeostasis, in part owing to a reduction in circulating 17β-estradiol (E). Fasting hyperglycemia is a hallmark of T2D derived largely from dysregulation of hepatic glucose production (HGP), in which Foxo1 plays a central role in the regulation of gluconeogenesis. Here, we investigated the action of E on glucose homeostasis in male and ovariectomized (OVX) female control and liver-specific Foxo1 knockout (L-F1KO) mice, and sought to understand the mechanism by which E regulates gluconeogenesis via an interaction with hepatic Foxo1. Read More

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November 2018
2 Reads

Noninvasive Imaging of Endothelial Damage in Patients with different HbA1c-levels, a Proof-of-Concept Study.

Diabetes 2018 Nov 28. Epub 2018 Nov 28.

King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom.

The aim of this study was to compare endothelial permeability, which is considered a hallmark of CAD, between patients with different HbA1c-levels using an albumin-binding-MR-probe. This cross-sectional-study included 26 patients with clinical indication for x-ray-angiography, which were classified into 3 groups according to their HbA1c-levels (HbA1c<5.7%,<39mmol/mol; HbA1c=5. Read More

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November 2018

Multiethnic Genome-wide Association Study of Diabetic Retinopathy using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control.

Diabetes 2018 Nov 28. Epub 2018 Nov 28.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large, multiethnic genome-wide association study (GWAS). Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Read More

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November 2018
1 Read
8.095 Impact Factor

Dynamic Contrast-Enhanced Magnetic Resonance Imaging of OATP Dysfunction in Diabetes.

Diabetes 2018 Nov 28. Epub 2018 Nov 28.

Department of Radiology, Michigan State University, East Lansing, MI

Diabetes mellitus is associated with hepatic metabolic dysfunction predisposing patients to drug induced liver injury. Mouse models of Type 2 diabetes (T2D) have dramatically reduced expression of Organic Anion Transporting Polypeptide (OATP) 1A1, a transporter expressed in hepatocytes and in the kidneys. Effects of diabetes on OATP1B2 expression are less studied and less consistent. Read More

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November 2018
3 Reads

Response to Comment on Bu et al. Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/Differentiation Factor 3 in Adipose Tissue Macrophages. Diabetes 2018;67:1761-1772.

Authors:
Tetsuro Izumi

Diabetes 2018 Dec;67(12):e2-e3

Laboratory of Molecular Endocrinology and Metabolism, Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, and Research Program for Signal Transduction, Division of Endocrinology, Metabolism and Signal Research, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Japan

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December 2018

Comment on Bu et al. Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/Differentiation Factor 3 in Adipose Tissue Macrophages. Diabetes 2018;67:1761-1772.

Diabetes 2018 Dec;67(12):e1

Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden; Life Sciences Institute, National University of Singapore, Singapore; and Department of Physiology, National University of Singapore, Singapore

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December 2018

Targeting Metabolism, Insulin Resistance, and Diabetes to Treat Nonalcoholic Steatohepatitis.

Authors:
Brian N Finck

Diabetes 2018 Dec;67(12):2485-2493

Center for Human Nutrition, Division of Geriatrics and Nutritional Sciences, John T. Milliken Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO

Obesity, insulin resistance, and diabetes are strongly linked to the accumulation of excessive lipids in the liver parenchyma, a condition known as nonalcoholic fatty liver disease (NAFLD). Given its association with obesity and related metabolic diseases, it is not surprising that the prevalence of NAFLD has dramatically increased in the past few decades. NAFLD has become the most common liver disease in many areas of the world. Read More

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December 2018
1 Read

In This Issue of .

Authors:

Diabetes 2018 Dec;67(12):2483-2484

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December 2018

Adipocyte Glucocorticoid Receptor Deficiency Promotes Adipose Tissue Expandability and Improves the Metabolic Profile Under Corticosterone Exposure.

Diabetes 2018 Nov 19. Epub 2018 Nov 19.

Sorbonne University, INSERM, Saint-Antoine Research Center (CRSA), Paris, France

Widely used for their anti-inflammatory and immunosuppressive properties, glucocorticoids are nonetheless responsible for the development of diabetes and lipodystrophy. Despite an increasing number of studies focused on the adipocyte glucocorticoid receptor (GR), its precise role in the molecular mechanisms of these complications remains unclear. In keeping with this goal, we generated a conditional adipocyte-specific murine model of GR invalidation (AdipoGR-knock-out [KO] mice). Read More

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November 2018
3 Reads
8.095 Impact Factor

HSPA12A is a Novel Player in Nonalcoholic Steatohepatitis via Promoting Nuclear PKM2-mediated M1 Macrophage Polarization.

Diabetes 2018 Nov 19. Epub 2018 Nov 19.

Departments of Anesthesiology, Geriatrics and

Nonalcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease worldwide. Macrophage-mediated inflammation plays a critical role in NASH pathogenesis; however, optimum therapies for macrophage activation and NASH remain elusive. Heat shock protein 12A (HSPA12A) encodes a novel member of the HSP70 family. Read More

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November 2018
3 Reads

Post-Transplant Characterization of Long-Term Functional hESC-Derived Pancreatic Endoderm Grafts.

Diabetes 2018 Nov 19. Epub 2018 Nov 19.

Clinical Islet Transplant Program, University of Alberta, 112 Street & 87 Avenue, Edmonton, AB, Canada, T6G 2E1.

The paucity of human donors confines the broadened application of β-cell replacement therapy. Insulin-producing cells derived from human embryonic stem cells (hESC), have been recently investigated clinically as a feasible surrogate to primary tissue. Herein, we examine the long-term efficacy of hESC derived pancreatic endoderm cells (PEC) to maintain normoglycemia post-transplant and characterize graft's phenotype. Read More

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November 2018
3 Reads

The Familiality of Rapid Renal Decline in Diabetes.

Diabetes 2018 Nov 13. Epub 2018 Nov 13.

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah;

Sustained and rapid loss of glomerular filtration rate (GFR) is the predominant clinical feature of diabetic kidney disease and a requisite for the development of end-stage renal disease. While GFR trajectories have been studied in several diabetic and non-diabetic cohorts, whether rapid renal decline clusters in diabetic families has not been examined. To determine this, we estimated GFR (eGFR) from serum creatinine measurements obtained from 15,612 patients with diabetes at the University of Utah Health Sciences Center and established their renal function trajectories. Read More

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November 2018
6 Reads

NLRP3 Promotes Diabetic Bladder Dysfunction and Changes in Symptom-Specific Bladder Innervation.

Diabetes 2018 Nov 13. Epub 2018 Nov 13.

Department of Surgery, Division of Urology, Duke University Medical Center, Durham, NC.

The NLRP3 inflammasome senses diabetic metabolites and initiates inflammation implicated in diabetic complications and neurodegeneration. No studies have investigated NLRP3 in diabetic bladder dysfunction (DBD), despite a high clinical prevalence. , we found that numerous diabetic metabolites activate NLRP3 in primary urothelial cells. Read More

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November 2018
4 Reads

WASH Regulates Glucose Homeostasis by Facilitating Glut2 Receptor Recycling in Pancreatic Beta Cells.

Diabetes 2018 Nov 13. Epub 2018 Nov 13.

Division of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN 55905

WASH is an endosomal protein belonging to the Wiskott-Aldrich syndrome protein superfamily that participates in endosomal receptor trafficking by facilitating tubule fission via activation of the ubiquitously expressed Arp2/3 complex. While several studies have begun to understand the functions of WASH in cells lines, the in vivo function of WASH has not been fully elucidated since total body deletion in mice leads to early embryonic lethality. To circumvent this problem, we have used a WASH conditional knockout mouse model to investigate the role of WASH in the pancreas. Read More

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November 2018
5 Reads

Targeting the CDA1/CDA1BP1 Axis Retards Renal Fibrosis in Experimental Diabetic Nephropathy.

Diabetes 2018 Nov 13. Epub 2018 Nov 13.

Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia.

Targeting Cell Division Autoantigen 1 (CDA1) is postulated to attenuate the profibrotic actions of transforming growth factor-β in diabetic nephropathy. This study has identified a regulatory protein for CDA1 and has then used genetic and pharmacological approaches to test if strategies to target this pathway would lead to reduced renal injury. A novel protein, named CDA1BP1, was identified as critical in regulating the profibrotic activity of CDA1. Read More

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November 2018
5 Reads

"Examining How the MAFB Transcription Factor Affects Islet β Cell Function Postnatally".

Diabetes 2018 Nov 13. Epub 2018 Nov 13.

Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN

The sustained expression of the MAFB transcription factor in human islet β cells represents a distinct difference to mouse. Moreover, mRNA expression of closely related and islet β cell-enriched MAFA does not peak in humans until after nine years in age. Here we show that the MAFA protein is also weakly produced within the juvenile human islet β cell population, and that expression is postnatally restricted in mouse β cells by DNA methylation. Read More

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November 2018
10 Reads

A Network Analysis of Biomarkers for Type 2 Diabetes.

Diabetes 2018 Nov 8. Epub 2018 Nov 8.

South Australian Health and Medical Research Institute, Adelaide, Australia.

Numerous studies have investigated individual biomarkers in relation to risk of type 2 diabetes. However, few have considered the interconnectivity of these biomarkers in the etiology of diabetes as well as the potential changes in the biomarker correlation network during diabetes development. We conducted a secondary analysis of 27 plasma biomarkers representing glucose metabolism, inflammation, adipokines, endothelial dysfunction, insulin-like growth factor axis and iron store plus age and BMI at blood collection from an existing case-control study nested in the Nurses' Health Study, including 1,303 incident diabetes cases and 1,627 healthy women. Read More

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November 2018
3 Reads

TGR5 Activation Promotes Stimulus-Secretion Coupling of Pancreatic Beta-Cells via a PKA-Dependent Pathway.

Diabetes 2018 Nov 8. Epub 2018 Nov 8.

Institute of Pharmacy, Department of Pharmacology, University of Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany

The Takeda-G-protein-receptor-5 (TGR5) mediates physiological actions of bile acids. Since it was shown that TGR5 is expressed in pancreatic tissue, a direct TGR5 activation in beta-cells is currently postulated and discussed. The present study reveals that oleanolic acid (OLA) affects murine beta-cell function by TGR5 activation. Read More

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November 2018
10 Reads

Risk Factor Modeling for Cardiovascular Disease in Type I Diabetes in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study: A Comparison to the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study.

Diabetes 2018 Nov 8. Epub 2018 Nov 8.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15260.

In a recent Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) report, mean HbA1c was the strongest predictor of cardiovascular disease (CVD) after age. In DCCT/EDIC, mean diabetes duration was 6 (median 4) years at baseline and those with high blood pressure or cholesterol were excluded. We now replicate these analyses in the Pittsburgh Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset (<17 years) type 1 diabetes, with similar age (mean 27 years in both studies) but longer diabetes duration (mean 19, median 18 years) and no CVD risk factor exclusion at baseline. Read More

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November 2018
3 Reads

Sex Differences in Coronary Microvascular Function in Individuals with Type 2 Diabetes Mellitus.

Diabetes 2018 Nov 8. Epub 2018 Nov 8.

Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Cardiovascular (CV) disease fatality rates are higher for women compared to men with diabetes despite lower rates of obstructive coronary artery disease (CAD). Impaired coronary flow reserve (CFR), the ratio of adenosine-stimulated to rest myocardial blood flow (MBF), is an indicator of coronary microvascular dysfunction and predicts major adverse CV events. We performed a post-hoc analysis to determine if there was a sex disparity in coronary microvascular dysfunction among 46 men and 27 women with well-controlled Type 2 DM and without clinical evidence of obstructive CAD. Read More

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November 2018
6 Reads

Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes.

Diabetes 2018 Nov 5. Epub 2018 Nov 5.

German Center for Diabetes Research (DZD), München-Neuherberg, Germany

Recent studies suggest that insulin-like growth factor binding protein-2 (IGFBP-2) may protect against type 2 diabetes but population-based human studies are scarce. We aimed to investigate the prospective association of circulating IGFBP-2 concentrations and of differential methylation in the gene with type 2 diabetes risk.Within the EPIC-Potsdam cohort (n=27,548), circulating IGFBP-2 concentration was assessed in a nested case-cohort (random subcohort, n=2500, all incident type 2 diabetes cases, n=820). Read More

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November 2018
6 Reads

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy. Results of the EUROCONDOR Clinical Trial.

Diabetes 2018 Nov 2. Epub 2018 Nov 2.

Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal, Faculty of Medicine, University of Coimbra, Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal.

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in diabetic patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥ 5 years, and an ETDRS level ≤35 were randomly assigned to one of 3 arms: placebo, somatostatin and brimonidine. The primary outcome was the change in Implicit Time (IT) assessed by mfERG between baseline and at the end of follow-up (96 weeks). Read More

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November 2018
1 Read

GLP-1 Receptor in Pancreatic α Cells Regulates Glucagon Secretion in a Glucose-Dependent Bidirectional Manner.

Diabetes 2018 Nov 2. Epub 2018 Nov 2.

Section of Endocrinology, Department of Medicine, Tulane University Health Science Center, New Orleans, Louisiana

Glucagon-like peptide-1 (GLP-1) is known to suppress glucagon secretion, but the mechanism by which GLP-1 exerts this effect is unclear. In this study, we demonstrated GLP-1R expression in α cells using both antibody-dependent and -independent strategies. A novel α cell specific GLP-1R knockout (αGLP-1R) mouse model was then created and used to investigate its effects on glucagon secretion and glucose metabolism. Read More

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November 2018
1 Read

DNA Sequence Variation in Encoding the Activin-Receptor Like Kinase 7 Influences Body Fat Distribution and Protects Against Type 2 Diabetes.

Diabetes 2018 Nov 2. Epub 2018 Nov 2.

Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 (Emdin, Khera, Klarin, Natarajan, Aragam, Haas, Bick, Zekavat, Nomura, Kathiresan)

A genetic predisposition to higher waist-to-hip ratio adjusted for body mass index (WHRadjBMI), a measure of body fat distribution, associates with increased risk for type 2 diabetes. We conducted an exome-wide association study of coding variation in UK Biobank (405569 individuals) to identify variants that lower WHRadjBMI and protect against type 2 diabetes. We identified four variants in the gene , encoding the activin-receptor like kinase 7 receptor expressed on adipocytes and pancreatic beta cells, which independently associated with reduced WHRadjBMI: Asn150His (-0. Read More

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November 2018
2 Reads

Senescent T Cells Predict the Development of Hyperglycemia in Humans.

Diabetes 2018 Nov 2. Epub 2018 Nov 2.

Severance Hospital, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea

Senescent T cells have been implicated in chronic inflammatory and cardiovascular diseases. Here, we explored the relationship between senescent T cells and glycemic status in a cohort of 805 participants by investigating the frequency of CD57 or CD28 senescent T cells in peripheral blood. Normal glucose tolerance (NGT) participants with follow-up data (N = 149) were included to determine whether hyperglycemia (prediabetes or type 2 diabetes) developed during follow-up (mean 2. Read More

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November 2018
4 Reads

VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy.

Diabetes 2018 Nov 2. Epub 2018 Nov 2.

Bristol Renal, Bristol Heart Institute, Translational Health Sciences, Bristol Medical School, Dorothy Hodgkin Building, Whitson St, Bristol, BS1 3NY

Elevated levels of vascular endothelial growth factor (VEGF)A are thought to cause glomerular endothelial cell (GEnC) dysfunction and albuminuria in diabetic nephropathy. We hypothesized that VEGFC could counteract these effects of VEGFA to protect the glomerular filtration barrier and reduce albuminuria. Isolated glomeruli were stimulated with VEGFC, which reduced VEGFA- and type II diabetes-induced glomerular albumin permeability (Ps'alb). Read More

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November 2018
2 Reads

An Integrated Understanding of the Molecular Mechanisms How Adipose Tissue Metabolism Affects Long-Term Body Weight Maintenance.

Diabetes 2018 Nov 2. Epub 2018 Nov 2.

Department of Endocrinology & Metabolism, Charité - Universitätsmedizin Berlin, Germany.

Life-style based weight loss interventions frequently demonstrate long-term inefficiency and weight regain. Identification of underlying mechanisms and predictors to identify subjects who will benefit from life-style based weight loss strategies is urgently required. We analyzed 143 adults of the randomized Maintain trial (Maintain-Adults) after intended weight loss to identify mechanisms contributing to the regulation of body weight maintenance. Read More

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November 2018
4 Reads

Fibro-Adipogenic Remodeling of the Diaphragm in Obesity-Associated Respiratory Dysfunction.

Diabetes 2018 Oct 25. Epub 2018 Oct 25.

Division of Metabolism Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI

Respiratory dysfunction is a common complication of obesity, conferring cardiovascular morbidity, increased mortality and often necessitating mechanical ventilatory support. While impaired lung expansion in the setting of increased adipose mass and reduced central response to hypercapnia have been implicated as pathophysiological drivers, the impact of obesity on respiratory muscles-in particular, the diaphragm-has not been investigated in detail. Here, we demonstrate that chronic high-fat diet (HFD)-feeding impairs diaphragm muscle function, as assessed by ultrasonography and by measurement of contractile force. Read More

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October 2018
4 Reads

Dysregulation of Nrf2/Keap1 Redox Pathway in Diabetes Affects Multipotency of Stromal Cells.

Diabetes 2018 Oct 23. Epub 2018 Oct 23.

Hansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, New York, NY 10016

The molecular and cellular level reaches of the metabolic dysregulations that characterize diabetes are yet to be fully discovered. As mechanisms underlying management of reactive oxygen species (ROS) gain interest as crucial factors in cell integrity, questions arise about the role of redox cues in regulation and maintenance of bone marrow-derived multipotent stromal cells (BMSCs) that contribute to wound healing, particularly in diabetes. Through comparison of BMSCs from wild type and diabetic mice, with a known redox and metabolic disorder, we found that the cytoprotective Nrf2/Keap1 pathway is dysregulated and functionally insufficient in diabetic BMSCs. Read More

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October 2018

Transient PAX8 Expression in Islets During Pregnancy Correlates With Beta Cell Survival Revealing a Novel Candidate Gene in Gestational Diabetes Mellitus.

Diabetes 2018 Oct 23. Epub 2018 Oct 23.

Pancreatic Islet Development and Regeneration Unit/Laboratory of Aging Biology, Centro Andaluz de Biologı́a Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain.

Transient Pax8 expression was reported in mouse islets during gestation while a genome-wide linkage and admixture mapping study highlighted PAX8 as candidate gene for diabetes mellitus (DM). Herein we sought the significance of PAX8 expression in mouse and human islet biology. Pax8 was induced in gestating mouse islets and in human islets treated with recombinant prolactin. Read More

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October 2018
7 Reads

Genome-Wide and Abdominal MRI-Imaging Data Provides Evidence that a Genetically Determined Favourable Adiposity Phenotype is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease and Hypertension.

Diabetes 2018 Oct 23. Epub 2018 Oct 23.

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK

Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such "favourable adiposity" alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined magnetic resonance imaging (MRI) data with genome-wide association studies (GWAS) of body fat % and metabolic traits. Read More

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October 2018
1 Read
8.100 Impact Factor

Circulating Phylloquinone Concentrations and Risk of Type 2 Diabetes: a Mendelian Randomization Study.

Diabetes 2018 Oct 23. Epub 2018 Oct 23.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands

This study aims to investigate the causal relation between circulating phylloquinone (vitamin K1) concentrations and type 2 diabetes using a Mendelian Randomization (MR) approach. We used data from thee cohorts: the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, Diabetes Genetics Replication and Meta-analysis (DIAGRAM) and the UK Biobank, resulting in 69,647 type 2 diabetes cases. We calculated a weighted genetic risk score including four genetic variants previously found to be associated with circulating phylloquinone concentrations. Read More

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October 2018

SREBP1c-PAX4 Axis Mediates Pancreatic β Cell Compensatory Responses Upon Metabolic Stress.

Diabetes 2018 Oct 23. Epub 2018 Oct 23.

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea;

Sterol responsive element-binding protein 1c (SREBP1c) is a key transcription factor for lipogenesis. Although SREBP1c is expressed in pancreatic islets, its physiological roles in pancreatic β cells are largely unknown. In this study, we demonstrate that SREBP1c regulates β cell compensation under metabolic stress. Read More

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October 2018
2 Reads

Inflammation-Induced Citrullinated Glucose-Regulated Protein 78 Elicits Immune Responses in Human Type 1 Diabetes.

Diabetes 2018 11;67(11):2337-2348

Laboratory for Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium

The β-cell has become recognized as a central player in the pathogenesis of type 1 diabetes with the generation of neoantigens as potential triggers for breaking immune tolerance. We report that posttranslationally modified glucose-regulated protein 78 (GRP78) is a novel autoantigen in human type 1 diabetes. When human islets were exposed to inflammatory stress induced by interleukin-1β, tumor necrosis factor-α, and interferon-γ, arginine residue R510 within GRP78 was converted into citrulline, as evidenced by liquid chromatography-tandem mass spectrometry. Read More

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November 2018
1 Read

Exosomes or Microvesicles, a Secreted Subcellular Organelle Contributing to Inflammation and Diabetes.

Diabetes 2018 11;67(11):2154-2156

Biomedical Research Institute of Southern California, San Diego, CA.

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November 2018

Mitochondrial ADP Sensitivity and Transport: New Insights Into Diet-Induced Mitochondrial Impairments.

Diabetes 2018 11;67(11):2152-2153

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine and Science, Rochester, MN

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November 2018

Developmental Programming of Obesity and Diabetes in Mouse, Monkey, and Man in 2018: Where Are We Headed?

Authors:
Jacob E Friedman

Diabetes 2018 11;67(11):2137-2151

Section of Neonatology, Department of Pediatrics; Department of Biochemistry & Molecular Genetics; Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; and Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO

Childhood obesity and its comorbidities continue to accelerate across the globe. Two-thirds of pregnant women are obese/overweight, as are 20% of preschoolers. Gestational diabetes mellitus (GDM) is escalating, affecting up to 1 in 5 pregnant women. Read More

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November 2018
5 Reads

Hepatic Insulin Clearance in Regulation of Systemic Insulin Concentrations-Role of Carbohydrate and Energy Availability.

Diabetes 2018 11;67(11):2129-2136

Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.

Hyperinsulinemia is the hallmark of insulin resistance in obesity, and the relative importance of insulin clearance, insulin resistance, and insulin hypersecretion has been widely debated. On the basis of recent experimental evidence, we summarize existing evidence to suggest hepatic insulin clearance as a major and immediate regulator of systemic insulin concentrations responding within days to altered dietary energy and, in particular, carbohydrate intake. Hepatic insulin clearance seems to be closely associated with opposite alterations in hepatic lipid content and glucose production, providing a potential mechanistic link to hepatic insulin sensitivity. Read More

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November 2018
7 Reads

In This Issue of .

Authors:

Diabetes 2018 11;67(11):2127-2128

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November 2018

Paternal Exercise Improves Glucose Metabolism in Adult Offspring.

Diabetes 2018 Dec 21;67(12):2530-2540. Epub 2018 Oct 21.

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA

Poor paternal diet has emerged as a risk factor for metabolic disease in offspring, and alterations in sperm may be a major mechanism mediating these detrimental effects of diet. Although exercise in the general population is known to improve health, the effects of paternal exercise on sperm and offspring metabolic health are largely unknown. Here, we studied 7-week-old C57BL/6 male mice fed a chow or high-fat diet and housed either in static cages (sedentary) or cages with attached running wheels (exercise trained). Read More

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December 2018
19 Reads

Adaptive β-Cell Neogenesis in the Adult Mouse in Response to Glucocorticoid-Induced Insulin Resistance.

Diabetes 2018 Oct 16. Epub 2018 Oct 16.

Sorbonne Université, INSERM, Saint-Antoine Research Center, Paris, France

Both type 1 and type 2 diabetes are characterized by deficient insulin secretion and decreased β-cell mass. Thus, regenerative strategies to increase β-cell mass need to be developed. To characterize mechanisms of β-cell plasticity, we studied a model of severe insulin resistance in the adult mouse and defined how β-cells adapt. Read More

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October 2018
1 Read

Glycemic Variability and Brain Glucose Levels in T1DM.

Diabetes 2018 Oct 16. Epub 2018 Oct 16.

Section of Endocrinology, Yale School of Medicine, New Haven, CT.

The impact of glycemic variability on brain glucose transport kinetics amongst T1DM individuals remains unclear. 14 individuals with T1DM (age 35±4 years, BMI 26.0±1. Read More

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October 2018
3 Reads

Time-Resolved Autoantibody Profiling Facilitates Stratification of Preclinical Type 1 Diabetes in Children.

Diabetes 2018 Oct 10. Epub 2018 Oct 10.

German Center for Diabetes Research (DZD), Neuherberg, Germany

Progression to clinical type 1 diabetes varies between children developing beta-cell autoantibodies. Differences in autoantibody patterns could relate to disease progression and etiology. Here we modeled complex longitudinal autoantibody profiles using a novel wavelet-based algorithm. Read More

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October 2018
7 Reads

Genetic Regulation of Pigment Epithelium-Derived Factor (PEDF): An Exome-Chip Association Analysis in Chinese Subjects with Type 2 Diabetes.

Diabetes 2018 Oct 10. Epub 2018 Oct 10.

Department of Medicine, the University of Hong Kong, Hong Kong, China;

Elevated circulating levels of pigment epithelium-derived factor (PEDF) have been reported in patients with type 2 diabetes (T2DM) and its associated microvascular complications. This study aimed to (i) identify the genetic determinants influencing circulating PEDF level in a clinical setting of T2DM; (ii) examine the relationship between circulating PEDF and diabetic complications; and (iii) explore the causal relationship between PEDF and diabetic complications. An exome-chip association study on circulating PEDF leve1 was conducted in 5385 Chinese subjects with T2DM. Read More

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October 2018
2 Reads

MANF is Required for the Postnatal Expansion and Maintenance of the Pancreatic β-Cell Mass in Mice.

Diabetes 2018 Oct 10. Epub 2018 Oct 10.

Institute of Biotechnology, HiLIFE, University of Helsinki, Finland.

Global lack of mesencephalic astrocyte-derived neurotropic factor (MANF) leads to progressive postnatal loss of β-cells mass and insulin-dependent diabetes in mice. Similarly to mice, embryonic ablation of MANF specifically from the pancreas results in diabetes. In this study, we assessed the importance of MANF for the postnatal expansion of the pancreatic β-cell mass and for adult β-cell maintenance in mice. Read More

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October 2018

Loss of Nuclear and Membrane Estrogen Receptor-α Differentially Impairs Insulin Secretion and Action in Male and Female Mice.

Diabetes 2018 Oct 10. Epub 2018 Oct 10.

Section of Endocrinology and Metabolism, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA,

Estrogens favor glucose homeostasis primarily through the estrogen receptor alpha (ERα), but the respective importance of nuclear and membrane ERα pools to glucose homeostasis are unknown. We studied glucose homeostasis, insulin secretion and insulin sensitivity in male and female mice expressing either the nuclear ERα (NOER) or the membrane ERα (MOER). Male and female MOER mice exhibited fasting and fed hyperglycemia and glucose intolerance. Read More

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October 2018