16,323 results match your criteria Diabetes[Journal]


Low-dose Anti-Thymocyte Globulin Preserves C-Peptide and Reduces A1c in New Onset Type 1 Diabetes: Two Year Clinical Trial Data.

Diabetes 2019 Apr 9. Epub 2019 Apr 9.

From the University of Florida Diabetes Institute, Gainesville, FL (M.J.H., D.A.S. M.A.A.), Benaroya Research Institute, Seattle, WA (S.A.L, L.B. and C.J.G), Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, (J.S.S., D.B., J.B.M.), University of South Florida, Tampa, FL (J.P.K, B.N.B., S.M.G., M.W., J.L.M., H.R.), University of Pittsburgh, Pittsburgh, PA (D.J.B.), Indiana University, Indianapolis, IN (L.A.D.), University of California San Francisco, San Francisco, CA (S.E.G.), Columbia University, New York, NY (R.G.), University of Colorado Barbara Davis Center for Childhood Diabetes, Aurora, CO, (P.A.G.), Yale University, New Haven, CT (K.C.H.), University of Minnesota, Minneapolis, MN, (A.M.), Vanderbilt University, Nashville, TN (W.E.R.), The National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (L.M.S.), and Stanford University, Stanford, CA (D.M.W.).

A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG, 2.5mg/kg) preserved β-cell function and reduced HbA1c for one year in new-onset type 1 diabetes. Subjects (N=89) were randomized to: 1) ATG and pegylated granulocyte-colony stimulating factor (GCSF); 2) ATG alone; or 3) placebo. Read More

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http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db19
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http://dx.doi.org/10.2337/db19-0057DOI Listing
April 2019
1 Read

Trisomy 21 is a Cause of Permanent Neonatal Diabetes that is Autoimmune but not HLA Associated.

Diabetes 2019 Apr 8. Epub 2019 Apr 8.

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK

Identifying new causes of permanent neonatal diabetes (diagnosis <6 months; PNDM) provides important insights into β-cell biology. Patients with Down syndrome (DS) resulting from trisomy 21 are 4 times more likely to have childhood diabetes with an intermediate HLA association. It is not known if DS can cause PNDM. Read More

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http://dx.doi.org/10.2337/db19-0045DOI Listing
April 2019
8.095 Impact Factor

Genetic Variation Within the Gene Modulates Susceptibility to Type 1 Diabetes in HLA-DR3 Homozygotes.

Diabetes 2019 Apr 8. Epub 2019 Apr 8.

Department of Medicine and Endocrinology, University of Massachusetts Medical School, Worcester, MA

Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci T1D encode the Human Leukocyte Antigens HLA-DR and DQ. Genetic heterogeneity and linkage disequilibrium in the highly polymorphic HLA region confound attempts to identify additional T1D susceptibility loci. Read More

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http://dx.doi.org/10.2337/db18-1128DOI Listing

Heterogeneity of the Human Pancreatic Islet.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Department of Medicine, The University of Chicago, Chicago, Illinois 60637

Pancreatic beta-cells play a pivotal role in maintaining normoglycemia. Recent studies have revealed that the beta-cell is not a homogeneous cell population, but heterogeneous in a number of properties such as electrical activity, gene expression and cell surface markers. Identification of specific beta-cell subpopulations altered in diabetic conditions would open a new avenue to develop targeted therapeutic interventions. Read More

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http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db19
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http://dx.doi.org/10.2337/db19-0072DOI Listing
April 2019
4 Reads

Deficiency of ZnT8 Promotes Adiposity and Metabolic Dysfunction by Increasing Peripheral Serotonin Production.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Center for Diabetes, Obesity and Metabolism, Department of Physiology, Shenzhen University Health Science Center, Shenzhen, Guangdong province, China

ZnT8 is a zinc transporter enriched in the pancreatic beta cells and its polymorphism is associated with increased susceptibility to type 2 diabetes. However, the exact role of ZnT8 in systemic energy metabolism remains elusive. In this study, we found that ZnT8 knockout mice displayed increased adiposity without obvious weight gain. Read More

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http://dx.doi.org/10.2337/db18-1321DOI Listing
April 2019
8.095 Impact Factor

Identification of Insulin-Responsive Transcription Factors Regulating Hepatocyte Glucose Production.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Department of Medicine and

Hepatocyte glucose production is a complex process that integrates cell-autonomous mechanisms with cellular signaling, modulation of enzyme activities, and gene transcription. Transcriptional mechanisms controlling glucose production are redundant, and involve nuclear hormone receptors as well as unliganded transcription factors (TFs). Our knowledge of this circuitry is incomplete. Read More

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http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db18
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http://dx.doi.org/10.2337/db18-1236DOI Listing
April 2019
6 Reads

Altered Lipid Fluxes and Cell Dynamics in Subcutaneous Adipose Tissues are Associated with the Unfavorable Pattern of Fat Distribution in Obese Adolescent Girls

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Department of Pediatrics, Division of Pediatric Endocrinology, Yale University School of Medicine, New Haven (CT), USA

Patterns of abdominal fat distribution, [for example: a high vs low VAT/(VAT+SAT) ratio] independent of obesity, during adolescence carry a high risk for insulin resistance (IR) and type 2 diabetes. Longitudinal follow-up of a cohort of obese adolescents has recently revealed that a high ratio (high VAT/(VAT+SAT) is a major determinant of fatty liver and metabolic impairment over time, with these effects being more pronounced in girls than in boys. To unravel the underlying metabolic alterations associated with the unfavorable VAT/(VAT+SAT) phenotype, we used the HO labeling method to measure the turnover of adipose lipids and cells in the subcutaneous abdominal and gluteal/femoral adipose tissue (SAT) of weight stable obese adolescent girls with similar level of obesity but discordant VAT/(VAT+SAT) ratios. Read More

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http://dx.doi.org/10.2337/db18-1162DOI Listing
April 2019
1 Read

T Cell-Specific PTPN2-Deficiency in NOD Mice Accelerates the Development of Type 1 Diabetes and Autoimmune Co-Morbidities.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia,

Genome-wide association studies have identified as an important non-major histocompatibility complex gene for autoimmunity. Single nucleotide polymorphisms that reduce expression have been linked with the development of varied autoimmune disorders, including type 1 diabetes. The tyrosine-phosphatase PTPN2 attenuates T cell receptor and cytokine signalling in T cells to maintain peripheral tolerance, but the extent to which PTPN2-deficiency in T cells might influence type 1 diabetes onset remains unclear. Read More

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http://dx.doi.org/10.2337/db18-1362DOI Listing
April 2019
5 Reads

Hepatocyte-Specific Ablation or Whole Body Inhibition of Xanthine Oxidoreductase in Mice Corrects Obesity-Induced Systemic Hyperuricemia Without Improving Metabolic Abnormalities.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Department of Physiology and Pharmacology; West Virginia University, Health Sciences Center, Morgantown, WV

Systemic hyperuricemia (HyUA) in obesity/T2DM facilitated by elevated activity of xanthine oxidoreductase (XOR), which is the sole source of uric acid (UA) in mammals, has been proposed to contribute to the pathogenesis of insulin resistance/dyslipidemia in obesity. Here, the effects of hepatocyte-specific ablation of , the gene encoding XOR (HXO) and whole-body pharmacologic inhibition of XOR (febuxostat) on obesity-induced insulin resistance/dyslipidemia were assessed. Deletion of hepatocyte substantially lowered liver and plasma UA concentration. Read More

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http://dx.doi.org/10.2337/db18-1198DOI Listing
April 2019
3 Reads

Diabetes-Associated Myelopoiesis Drives Stem Cell Mobilopathy Through an OSM-p66Shc Signaling Pathway.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Veneto Institute of Molecular Medicine (VIMM), 35129 Padova, Italy

Diabetes impairs the mobilization of hematopoietic stem/progenitor cells (HSPCs) from the bone marrow (BM), which can worsen the outcomes of HSPC transplantation and of diabetic complications. In this study, we examined the oncostatin M (OSM) - p66Shc pathway as a mechanistic link between HSPC mobilopathy and excessive myelopoiesis. We found that streptozotocin (STZ)-induced diabetes in mice skewed hematopoiesis towards the myeloid lineage, via hematopoietic-intrinsic p66Shc. Read More

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http://dx.doi.org/10.2337/db19-0080DOI Listing

Sympathetic Denervation of the Common Hepatic Artery Lessens Glucose Intolerance in the Fat and Fructose Fed Dog.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.

This study assessed the effectiveness of surgical sympathetic denervation of the common hepatic artery (CHADN) in improving glucose tolerance. CHADN eliminated norepinephrine (NE) content in the liver and partially decreased it in the pancreas and the upper gut. We assessed oral glucose tolerance at baseline and after 4 wk of high fat high fructose feeding (HFHF). Read More

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http://dx.doi.org/10.2337/db18-1209DOI Listing
April 2019
1 Read

Long Acting Neurotensin Synergizes with Liraglutide to Reverse Obesity Through a Melanocortin-Dependent Pathway.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.

Neurotensin, a gut hormone and neuropeptide, increases in circulation after bariatric surgery in rodents and humans and inhibits food intake in mice. However, its potential to treat obesity and the subsequent metabolic dysfunctions have been difficult to assess owing to its short half-life Here, we demonstrate that a long acting, pegylated analogue of the neurotensin peptide (P-NT) reduces food intake, body weight and adiposity in diet-induced obese (DIO) mice when administered once daily for 6 days. Strikingly, when P-NT was combined with the GLP-1 mimetic liraglutide the two peptides synergized to reduce food intake and body weight relative to each mono-therapy, without inducing a taste aversion. Read More

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http://dx.doi.org/10.2337/db18-1009DOI Listing
April 2019
1 Read

A Peripheral Blood DNA Methylation Signature of Hepatic Fat Reveals a Potential Causal Pathway for Nonalcoholic Fatty Liver Disease.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, and Framingham Heart Study, Framingham, MA

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Read More

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http://dx.doi.org/10.2337/DB18-1193DOI Listing
April 2019
1 Read

Skeletal Muscle-Specific Activation of G Signaling Maintains Glucose Homeostasis.

Diabetes 2019 Apr 1. Epub 2019 Apr 1.

Molecular Signaling Section, Laboratory of Bioorganic Chemistry, and

Skeletal muscle (SKM) insulin resistance plays a central role in the pathogenesis of type 2 diabetes. Since G protein-coupled receptors (GPCRs) represent excellent drug targets, we hypothesized that activation of specific functional classes of SKM GPCRs might lead to improved glucose homeostasis in type 2 diabetes. At present, little is known about the metabolic roles of the various distinct GPCR signaling pathways operative in SKM. Read More

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http://dx.doi.org/10.2337/db18-0796DOI Listing
April 2019
3 Reads

In This Issue of .

Authors:

Diabetes 2019 Apr;68(4):679-680

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http://dx.doi.org/10.2337/db19-ti04DOI Listing

Celastrol Reduces Obesity in MC4R Deficiency and Stimulates Sympathetic Nerve Activity Affecting Metabolic and Cardiovascular Functions.

Diabetes 2019 Mar 20. Epub 2019 Mar 20.

Departments of Pharmacology,

Leptin resistance is a hallmark of obesity with unclear etiology. Celastrol, a compound found in the roots of the Tripterygium wilfordii and known to reduce ER stress, has recently emerged as a promising candidate to treat obesity by improving leptin sensitivity. However, the underlying neural mechanisms by which Celastrol reduces obesity remain unclear. Read More

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http://dx.doi.org/10.2337/db18-1167DOI Listing

Dynamic Immune Phenotypes of B and T Helper Cells Mark Distinct Stages of T1D Progression.

Diabetes 2019 Mar 20. Epub 2019 Mar 20.

Translational Research Program, Benaroya Research Institute, Seattle, WA, 98101, USA;

Multiple studies of B and T cell compartments and their response to stimuli demonstrate alterations in established Type 1 Diabetes (T1D). Yet it is not known whether these alterations reflect immune mechanisms that initiate islet autoimmunity, promote disease progression or are secondary to disease. To address these questions, we utilized samples from the TrialNet Pathway to Prevention study to investigate T cell responses to IL-2 and Treg mediated suppression, the composition of the B cell compartment, and B cell responses to BCR and IL-21 receptor engagement. Read More

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http://dx.doi.org/10.2337/db18-1081DOI Listing

Ameliorating Methylglyoxal-Induced Progenitor Cell Dysfunction for Tissue Repair in Diabetes.

Diabetes 2019 Mar 18. Epub 2019 Mar 18.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences;

Patient-derived progenitor cell (PC) dysfunction is severely impaired in diabetes, but the molecular triggers that contribute to mechanisms of PC dysfunction are not fully understood. Methylglyoxal (MGO) is one of the highly reactive dicarbonyl species formed during hyperglycemia. We hypothesize that the MGO scavenger glyoxalase 1 (GLO1) reverses bone marrow-derived progenitor cell (BMPCs) dysfunction through augmenting the activity of an important endoplasmic reticulum (ER) stress sensor, inositol-requiring enzyme 1α (IRE1α), resulting in improved diabetic wound healing. Read More

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http://dx.doi.org/10.2337/db18-0933DOI Listing
March 2019
1 Read

Nine Amino Acids are Associated with Decreased Insulin Secretion and Elevated Glucose Levels in a 4.6-Year Follow-Up Study of 5,181 Finnish Men.

Diabetes 2019 Mar 18. Epub 2019 Mar 18.

Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland

Several amino acids have been shown to be associated with insulin resistance and increased risk of type 2 diabetes, but none of previous studies has investigated the association of amino acids with insulin secretion in a longitudinal setting. Our study included 5181 participants of the cross-sectional METabolic Syndrome In Men study having metabolomics data on twenty amino acids. A total of 4851 of them had a 4. Read More

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http://dx.doi.org/10.2337/db18-1076DOI Listing

Cardiac Autonomic Function is Associated With Myocardial Flow Reserve in Type 1 Diabetes.

Diabetes 2019 Mar 12. Epub 2019 Mar 12.

Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, 2820 Gentofte, Denmark.

The link between cardiac autonomic neuropathy and risk of cardiovascular disease is highlighted as an area in which research is needed. This study was undertaken to evaluate the association between measures of cardiac autonomic function and cardiac vascular function in type 1 diabetes using new and sensitive methods.Cross-sectional study in type 1 diabetes, stratified by normoalbuminuria (n=30) and macroalbuminuria (n=30), and in healthy controls (n=30). Read More

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http://dx.doi.org/10.2337/db18-1313DOI Listing

A Unique Role of Carboxylesterase 3 (Ces3) in β-Adrenergic Signaling Stimulated Thermogenesis.

Diabetes 2019 Mar 12. Epub 2019 Mar 12.

Center for Metabolic and Degenerative Diseases, the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, USA

Carboxylesterase 3 (Ces3) is a hydrolase with a wide range of activities in liver and adipose tissue. Here, we identified Ces3 as a major lipid droplet surface targeting protein in adipose tissue upon cold exposure by LC-MS/MS. To investigate the function of Ces3 in the β-adrenergic signaling activated adipocytes, we applied WWL229, a specific Ces3 inhibitor, or genetic inhibition by siRNA to on isoproterenol (ISO) treated 3T3-L1 and BAC (brown adipocytes) cells. Read More

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http://dx.doi.org/10.2337/db18-1210DOI Listing
March 2019
4 Reads
8.095 Impact Factor

Fpr2 Deficiency Alleviates Diet-Induced Insulin Resistance Through Reducing Body Weight Gain and Inhibiting Inflammation Mediated by Macrophage Chemotaxis and M1 Polarization.

Diabetes 2019 Mar 12. Epub 2019 Mar 12.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences

Obesity and related inflammation are critical for the pathogenesis of insulin resistance, but the underlying mechanisms are not fully understood. Formyl peptide receptor 2 (FPR2) plays important roles in host immune responses and inflammation-related diseases. We found that Fpr2 expression was elevated in the white adipose tissue of high fat diet (HFD)-induced obese mice and mice. Read More

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http://dx.doi.org/10.2337/db18-0469DOI Listing
March 2019
2 Reads

FGF19 Analogue as a Surgical Factor Mimetic that Contributes to Metabolic Effects Beyond Glucose Homeostasis.

Diabetes 2019 Mar 12. Epub 2019 Mar 12.

NGM Biopharmaceuticals, 333 Oyster Point Blvd., South San Francisco, CA, USA

Bariatric surgery has proven to be the most effective treatment for controlling hyperglycemia in severely obese diabetic patients. Here we show that FGF19, a gut hormone, is rapidly induced by bariatric surgery in rodents and humans. Administration of FGF19 achieves diabetes remission independent of weight loss in animal models of diabetes, supporting a role for FGF19 in the hormonal remodeling that restores metabolic function following the surgery. Read More

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http://dx.doi.org/10.2337/db18-1305DOI Listing
March 2019
1 Read

A Thermogenic-Like Brown Adipose Tissue Phenotype is Dispensable for Enhanced Glucose Tolerance in Female Mice.

Diabetes 2019 Mar 12. Epub 2019 Mar 12.

Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA

The prevailing dogma is that thermogenic brown adipose tissue (BAT) contributes to improvements in glucose homeostasis in obesogenic animal models; though, much of the evidence supporting this premise is from thermostressed rodents. Whether modulation of the BAT morphology/function drives changes in glucoregulation at thermoneutrality requires further investigation. We utilized loss and gain-of-function approaches including genetic manipulation of the lipolytic enzyme , change in environmental temperature, and lifestyle interventions to comprehensively test the premise that a thermogenic-like BAT phenotype is coupled with enhanced glucose tolerance in female mice. Read More

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http://dx.doi.org/10.2337/db18-1070DOI Listing
March 2019
2 Reads

Diabetes-Induced DUSP4 Reduction Promotes Podocyte Dysfunction and Progression of Diabetic Nephropathy.

Diabetes 2019 Mar 12. Epub 2019 Mar 12.

From the Research Center of the Centre Hospitalier Universitaire de Sherbrooke and

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease. Hyperglycemia-induced podocyte dysfunction is a major contributor of renal function impairment in DN. Previous studies showed that activation of mitogen-activated protein kinase (MAPK) in diabetes promotes podocyte dysfunction and cell death. Read More

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http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db18
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http://dx.doi.org/10.2337/db18-0837DOI Listing
March 2019
4 Reads

HLA Class II Antigen Processing and Presentation Pathway Components Demonstrated by Transcriptome and Protein Analyses of islet β-Cells from Donors with Type 1 Diabetes.

Diabetes 2019 Mar 4. Epub 2019 Mar 4.

Department of Medicine, Division of Diabetes, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA

Type 1 diabetes studies consistently generate data showing islet β-cell dysfunction and T-cell mediated anti-β-cell specific autoimmunity. To explore the pathogenesis, we interrogated the β-cell transcriptomes from donors with and without type 1 diabetes using both bulk-sorted and single β-cells. Consistent with immunohistological studies, β-cells from donors with type 1 diabetes displayed increased Class I transcripts and associated mRNA species. Read More

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http://dx.doi.org/10.2337/db18-0686DOI Listing
March 2019
6 Reads
8.095 Impact Factor

Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, a Mechanism for Vitamin D Deficiency in Diabetes.

Diabetes 2019 Mar 4. Epub 2019 Mar 4.

Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, Oulu, Finland

Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes, however, the mechanisms remain uncertain. Here, we show that nutritional deprivation responsive mechanisms regulate vitamin D metabolism. Both fasting and diabetes suppressed hepatic cytochrome P450 (CYP) 2R1, the main vitamin D 25-hydroxylase, responsible for the first bioactivation step. Read More

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http://dx.doi.org/10.2337/db18-1050DOI Listing
March 2019
1 Read

DNA Damage Does Not Cause BrdU Labeling of Mouse or Human Beta Cells.

Diabetes 2019 Mar 4. Epub 2019 Mar 4.

Diabetes Center of Excellence in the Department of Medicine, University of Massachusetts Medical School, Worcester MA

Pancreatic beta cell regeneration, the therapeutic expansion of beta cell number to reverse diabetes, is an important goal. Replication of differentiated insulin-producing cells is the major source of new beta cells in adult mice and juvenile humans (1-3). Nucleoside analogs such as bromodeoxyuridine (BrdU), which are incorporated into DNA during S-phase, have been widely used to quantify beta cell proliferation. Read More

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http://dx.doi.org/10.2337/db18-0761DOI Listing

Loss-of-Function Mutation in Thiamine Transporter 1 in a Family with Autosomal Dominant Diabetes.

Diabetes 2019 Mar 4. Epub 2019 Mar 4.

Department of Medicine, Harvard Medical School, Boston, MA, 02215, USA.

Solute Carrier Family 19 Member 2 () encodes thiamine transporter 1 (THTR1), which facilitates thiamine transport across the cell membrane. homozygous mutations have been described as a cause of thiamine-responsive megaloblastic anemia (TRMA), an autosomal recessive syndrome characterized by megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Here we describe a loss-of-function mutation (c. Read More

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http://dx.doi.org/10.2337/db17-0821DOI Listing
March 2019
1 Read
8.095 Impact Factor

Glucagon Receptor Antagonist Stimulated α-Cell Proliferation is Severely Restricted with Advanced Age.

Diabetes 2019 Mar 4. Epub 2019 Mar 4.

McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Houston, TX, 77030

Glucagon-containing α-cells potently regulate glucose homeostasis but the developmental biology of α-cells in adults remains poorly understood. While Glucagon receptor antagonists (GRAs) have great potential as anti-diabetic therapies, murine and human studies have raised concerns that GRAs might cause uncontrolled α-cell growth. Surprisingly, previous rodent GRA studies were only performed in young mice, implying that the potential impact of GRAs to drive α-cell expansion in adult patients is unclear. Read More

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http://dx.doi.org/10.2337/db18-1293DOI Listing

Postprandial Aminogenic Insulin and Glucagon Secretion can Stimulate Glucose Flux in Humans.

Diabetes 2019 Mar 4. Epub 2019 Mar 4.

Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia.

Insulin and glucagon exert opposing actions on glucose metabolism and their secretion is classically viewed as being inversely regulated. This is, however, context specific as protein ingestion concomitantly stimulates euglycemic insulin and glucagon secretion. It remains enigmatic how euglycemia is preserved under these conditions. Read More

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http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db18
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http://dx.doi.org/10.2337/db18-1138DOI Listing
March 2019
3 Reads

The Hypothalamic Arcuate Nucleus-Median Eminence is a Target for Sustained Diabetes Remission Induced by Fibroblast Growth Factor 1.

Diabetes 2019 Feb 22. Epub 2019 Feb 22.

University of Washington Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA, USA.

In rodent models of type 2 diabetes (T2D), sustained remission of diabetic hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1). To identify the brain area(s) responsible for this effect, we first used immunohistochemistry to map the hypothalamic distribution of phosphoERK (pERK1/2), a marker of MAP kinase-ERK signal transduction downstream of FGF receptor activation. Twenty minutes after icv FGF1 injection in adult male Wistar rats, pERK1/2 staining was detected primarily in two hypothalamic areas: the arcuate nucleus and adjacent median eminence (ARC-ME), and the paraventricular nucleus (PVN). Read More

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http://dx.doi.org/10.2337/db19-0025DOI Listing
February 2019

Altered Gut Microbiota Activate and Expand Insulin B15-23-Reactive CD8+ T-Cells.

Diabetes 2019 Feb 22. Epub 2019 Feb 22.

Diabetes Research Group, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XN, Wales, UK

Insulin is a major autoantigen in type 1 diabetes, targeted by both CD8 and CD4 T-cells. We studied an insulin-reactive T-cell receptor (TCR) alpha-chain transgenic non-obese diabetic (NOD) mouse on a TCRCα and proinsulin2 (PI2)-deficient background, designated as NOD mice. These mice develop a low incidence of autoimmune diabetes. Read More

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http://dx.doi.org/10.2337/db18-0487DOI Listing
February 2019
1 Read

A Peripheral Blood DNA Methylation Signature of Hepatic Fat Reveals a Potential Causal Pathway for Non-Alcoholic Fatty Liver Disease.

Diabetes 2019 Feb 22. Epub 2019 Feb 22.

Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland and the Framingham Heart Study, Framingham, Massachusetts, USA

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes. We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Read More

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http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db18
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http://dx.doi.org/10.2337/db18-1193DOI Listing
February 2019
5 Reads

Leveraging Genetics to Improve Cardiovascular Health in Diabetes: The 2018 Edwin Bierman Award Lecture.

Authors:
Alessandro Doria

Diabetes 2019 Mar;68(3):479-489

Research Division, Joslin Diabetes Center, Boston, MA

The past decade has witnessed an exponential increase in our ability to search the genome for genetic factors predisposing to cardiovascular disease (CVD) and in particular coronary heart disease (CHD). Identifying these genes could lead to the development of innovative strategies to prevent the cardiovascular complications of diabetes by allowing us to ) create predictive algorithms for the identification of patients at especially high risk of CVD so that these individuals can undergo preventive interventions early in the natural history of the disease; ) discover as yet unknown disease pathways linking diabetes to atherosclerosis, which can be used as targets for the development of new CVD-preventing drugs specifically directed at subjects with diabetes; and ) devise personalized programs increasing the cost-effectiveness of preventive interventions by tailoring them to the genetic background of each patient. Substantial progress has been made in each of these three areas as exemplified by the recent development of a CHD genetic risk score improving CHD prediction among subjects with type 2 diabetes, the discovery of a diabetes-specific CHD locus on 1q25 pointing to glutamine synthase () and the γ-glutamyl cycle as key regulators of CHD risk in diabetes, and the identification of two genetic loci allowing the selection of patients with type 2 diabetes who may especially benefit from intensive glycemic control. Read More

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http://dx.doi.org/10.2337/dbi18-0036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385753PMC

Targeting the Brain to Cure Type 2 Diabetes.

Authors:
Bernard Thorens

Diabetes 2019 Mar;68(3):476-478

Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

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http://dx.doi.org/10.2337/dbi18-0051DOI Listing

Males Require Estrogen Signaling Too: Sexual Dimorphism in the Regulation of Glucose Homeostasis by Nuclear ERα.

Diabetes 2019 Mar;68(3):471-473

Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN

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http://dx.doi.org/10.2337/dbi18-0046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385747PMC

In This Issue of .

Authors:

Diabetes 2019 Mar;68(3):469-470

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http://dx.doi.org/10.2337/db19-ti03DOI Listing
March 2019
2 Reads

Melatonin Increases Brown Adipose Tissue Volume and Activity in Melatonin Deficient Patients: a Proof-of-Concept Study.

Diabetes 2019 Feb 14. Epub 2019 Feb 14.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, Universidade de São Paulo, Brazil.

Melatonin, a pineal hormone synthesized at night, is critical for the synchronization of circadian and seasonal rhythms, being a key regulator of energy metabolism in many animal species. Although studies in humans are lacking, several reports, mainly on hibernating animals, demonstrate that melatonin supplementation and short photoperiod increase brown adipose tissue (BAT) mass. The present proof-of-concept study is the first, to our knowledge, to evaluate BAT in melatonin non-proficient patients (radiotherapy or surgical removal of pineal gland) before and after daily melatonin (3 mg) replacement for three months. Read More

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http://dx.doi.org/10.2337/db18-0956DOI Listing
February 2019

Fenofibrate Rescues Diabetes-Related Impairment of Ischemia-Mediated Angiogenesis by PPARα-Independent Modulation of Thioredoxin Interacting Protein.

Diabetes 2019 Feb 14. Epub 2019 Feb 14.

Heart Research Institute, Newtown, NSW, Australia

Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, reduces lower limb amputations in patients with type 2 diabetes mellitus. The mechanism is, however, unknown. Here we demonstrate that fenofibrate markedly attenuates diabetes-related impairment of ischemia-mediated angiogenesis. Read More

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http://dx.doi.org/10.2337/db17-0926DOI Listing
February 2019

Glucose Metabolism is Required for Platelet Hyperactivation in a Murine Model of Type 1 Diabetes Mellitus.

Diabetes 2019 Feb 14. Epub 2019 Feb 14.

Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa

Patients with type 1 diabetes mellitus (T1DM) have increased thrombosis and platelet activation. The mechanisms for platelet hyperactivation in diabetes are incompletely understood. T1DM is accompanied by hyperglycemia, dyslipidemia, and increased inflammation, in addition to an altered hormonal milieu. Read More

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http://dx.doi.org/10.2337/db18-0981DOI Listing
February 2019
1 Read

Absence of TXNIP in Humans Leads to Lactic Acidosis and Low Serum Methionine Linked to Deficient Respiration on Pyruvate.

Diabetes 2019 Apr 12;68(4):709-723. Epub 2019 Feb 12.

Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

Thioredoxin-interacting protein (TXNIP) is an α-arrestin that can bind to and inhibit the antioxidant protein thioredoxin (TXN). TXNIP expression is induced by glucose and promotes β-cell apoptosis in the pancreas, and deletion of its gene in mouse models protects against diabetes. TXNIP is currently studied as a potential new target for antidiabetic drug therapy. Read More

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http://dx.doi.org/10.2337/db18-0557DOI Listing
April 2019
13 Reads

Takes New Steps to Increase Transparency and Reproducibility.

Authors:
Martin G Myers

Diabetes 2019 Apr 11;68(4):681-682. Epub 2019 Feb 11.

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http://dx.doi.org/10.2337/dbi19-0008DOI Listing
April 2019
1 Read

Comparison of Human and Murine Enteroendocrine Cells by Transcriptomic and Peptidomic Profiling.

Diabetes 2019 Feb 7. Epub 2019 Feb 7.

Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, U.K.

Enteroendocrine cells (EECs) produce hormones such as glucagon-like peptide 1 and peptide YY that regulate food absorption, insulin secretion, and appetite. Based on the success of glucagon-like peptide 1-based therapies for type 2 diabetes and obesity, EECs are themselves the focus of drug discovery programs to enhance gut hormone secretion. The aim of this study was to identify the transcriptome and peptidome of human EECs and to provide a cross-species comparison between humans and mice. Read More

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http://dx.doi.org/10.2337/db18-0883DOI Listing
February 2019
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Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy.

Diabetes 2019 Feb 6. Epub 2019 Feb 6.

Department of Ophthalmology, Medical College of Georgia, Augusta, University, Augusta, GA 30912

We have investigated the contributing role of monosodium urate (MSU) to the pathological processes associated with the induction of diabetic retinopathy (DR). In human retinas and vitreous from donors with DR, we have found a significant increase in MSU levels which correlated with the presence of inflammatory markers and enhanced expression of xanthine oxidase. Same elevation in MSU levels was also detected in serum and vitreous of streptozotocin-induced diabetic rats (STZ-rats) analyzed at 8 weeks of hyperglycemia. Read More

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http://dx.doi.org/10.2337/db18-0912DOI Listing
February 2019
3 Reads
8.095 Impact Factor

Proximal Tubular Cell-Specific Ablation of Carnitine Acetyltransferase Causes Tubular Disease and Secondary Glomerulosclerosis.

Diabetes 2019 Apr 6;68(4):819-831. Epub 2019 Feb 6.

Oxidative Stress and Disease Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA

Proximal tubular epithelial cells are highly energy demanding. Their energy need is covered mostly from mitochondrial fatty acid oxidation. Whether derailments in fatty acid metabolism and mitochondrial dysfunction are forerunners of tubular damage has been suggested but is not entirely clear. Read More

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http://dx.doi.org/10.2337/db18-0090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425873PMC
April 2019
3 Reads