Diabetes Peer-Reviewed Research

Erratum. Predisposition to Proinsulin Misfolding as a Genetic Risk to Diet-Induced Diabetes. Diabetes 2021;70: 2580–2594

Published on 2 years ago

Source: Diabetes Journal

The nutrient sensor mTORC1 regulates insulin secretion by modulating ss-cell autophagy

The dynamic regulation of autophagy in β-cells by cycles of fasting-feeding and its effects on insulin secretion are unknown. In β-cells mTORC1 is inhibited while fasting, and is rapidly stimulated during refeeding by a single amino acid, leucine, and glucose. Stimulation of mTORC1 by nutrients inhibited the autophagy initiator ULK1… Read more

Published on 3 years ago

Source: Diabetes Journal

Functional Gly297Ser Variant of the Physiological Dysglycemic Peptide Pancreastatin is a Novel Risk Factor for Cardiometabolic Disorders

Pancreastatin (PST), a chromogranin A (CHGA)-derived potent physiological dysglycemic peptide, regulates glucose/insulin homeostasis. We have identified a non-synonymous functional PST variant (p.Gly297Ser; rs9658664) that occurs in a large section of human populations. Association analysis of this single nucleotide polymorphism with cardiovascular/metabolic diseases states in Indian populations (n4300 subjects) displays elevated… Read more

Published on 3 years ago

Source: Diabetes Journal

Recessive Genome-wide Meta-analysis Illuminates Genetic Architecture of Type 2 Diabetes

Most genome-wide association studies (GWAS) of complex traits are performed using models with additive allelic effects. Hundreds of loci associated with type 2 diabetes have been identified using this approach. Additive models, however, can miss loci with recessive effects, thereby leaving potentially important genes undiscovered. We conducted the largest GWAS… Read more

Published on 3 years ago

Source: Diabetes Journal

SGLT2 Inhibition Increases Fasting Glucagon but Does Not Restore the Counterregulatory Hormone Response to Hypoglycemia in Participants with Type 1 Diabetes

Individuals with type 1 diabetes have an impaired glucagon counterregulatory response to hypoglycemia. Sodium-glucose cotransporter (SGLT) inhibitors increase glucagon concentrations. We evaluated whether SGLT inhibition restores the glucagon counterregulatory hormone response to hypoglycemia. Adults with type 1 diabetes (n = 22) were treated with the SGLT2 inhibitor dapagliflozin (5 mg… Read more

Published on 3 years ago

Source: Diabetes Journal

The Role of TRAP{gamma}/SSR3 in Preproinsulin Translocation into the Endoplasmic Reticulum

In the endoplasmic reticulum (ER), the Translocation-Associated Protein complex (TRAP, also called Signal sequence receptor, SSR) includes four integral membrane proteins TRAPα/SSR1, TRAPβ/SSR2 and TRAP/SSR4 with the bulk of their extramembranous portions primarily in the ER lumen, whereas the extramembranous portion of TRAP/SSR3 is primarily cytosolic. Individually diminished expression of… Read more

Published on 3 years ago

Source: Diabetes Journal

Adipose Tissue Inflammation is Not Related to Adipose Insulin Resistance in Humans

The role of adipose tissue (AT) inflammation on AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC5). We studied 86… Read more

Published on 3 years ago

Source: Diabetes Journal

The Role of TRAPγ/SSR3 in Preproinsulin Translocation into the Endoplasmic Reticulum

In the endoplasmic reticulum (ER), the Translocation-Associated Protein complex (TRAP, also called Signal sequence receptor, SSR) includes four integral membrane proteins TRAPα/SSR1, TRAPβ/SSR2 and TRAPδ/SSR4 with the bulk of their extramembranous portions primarily in the ER lumen, whereas the extramembranous portion of TRAPγ/SSR3 is primarily cytosolic. Individually diminished expression of… Read more

Published on 3 years ago

Source: Diabetes Journal

MG53 E3 Ligase-dead Mutant Protects Diabetic Hearts from Acute Ischemic/Reperfusion Injury and Ameliorates Diet-induced Cardiometabolic Damage

Cardiometabolic diseases, including diabetes and its cardiovascular complications, are the global leading cause of death, highlighting a major unmet medical need. Over the last decade, MG53, also named TRIM72, has emerged as a powerful agent for myocardial membrane repair and cardioprotection, but its therapeutic value is complicated by its E3… Read more

Published on 3 years ago

Source: Diabetes Journal

GRP75 Regulates Mitochondrial-Supercomplex Turnover to Modulate Insulin Sensitivity

GRP75, defined as a major component of both mitochondrial quality control system and mitochondria-associated membrane, plays a key role in mitochondrial homeostasis. In this study, we assessed the roles of GRP75, other than as a component, in insulin action in both in vitro and in vivo models with insulin resistance…. Read more

Published on 3 years ago

Source: Diabetes Journal

Genetic Control of Splicing at SIRPG Modulates Risk of Type 1 Diabetes

Signal regulatory protein SIRP (CD172G) is expressed on the surface of lymphocytes where it acts by engaging its ligand, CD47. SIRPG, which encodes SIRP, contains a non-synonymous coding variant, rs6043409, which is significantly associated with risk for type 1 diabetes. SIRPG produces multiple transcript isoforms via alternative splicing, all encoding… Read more

Published on 3 years ago

Source: Diabetes Journal

Genetic Control of Splicing at SIRPG Modulates Risk of Type 1 Diabetes

Signal regulatory protein SIRPγ (CD172G) is expressed on the surface of lymphocytes where it acts by engaging its ligand, CD47. SIRPG, which encodes SIRPγ, contains a non-synonymous coding variant, rs6043409, which is significantly associated with risk for type 1 diabetes. SIRPG produces multiple transcript isoforms via alternative splicing, all encoding… Read more

Published on 3 years ago

Source: Diabetes Journal

Ancestry-Matched and Cross-Ancestry Genetic Risk Scores of Type 2 Diabetes in Pregnant Women and Fetal Growth – a Study in an Ancestrally Diverse Cohort

Maternal genetic variants associated with offspring birth weight and adult type 2 diabetes (T2D) risk loci show some overlap. Whether T2D genetic risk influences longitudinal fetal weight and the gestational timing when these relationships begin is unknown. We investigated the associations of T2D genetic risk score (GRS) with longitudinal fetal… Read more

Published on 3 years ago

Source: Diabetes Journal

Syndromic Monogenic Diabetes Genes Should be Tested in Patients With a Clinical Suspicion of MODY

At present, outside of infancy, genetic testing for monogenic diabetes is typically for mutations in MODY genes that predominantly result in isolated diabetes. Monogenic diabetes syndromes are usually only tested when this is supported by specific syndromic clinical features. It is not known how frequently patients with suspected MODY have… Read more

Published on 3 years ago

Source: Diabetes Journal

The Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: a Multi-Cohort Non-Targeted Metabolomics Observational and Mendelian Randomization Study

Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma… Read more

Published on 3 years ago

Source: Diabetes Journal

Heterogeneity of Diabetes: {beta}-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases

One hundred years have passed since the discovery of insulin—an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the… Read more

Published on 3 years ago

Source: Diabetes Journal

Human Islet MicroRNA-200c is Elevated in Type 2 Diabetes and Targets the Transcription Factor ETV5 to Reduce Insulin Secretion

MicroRNAs (miRNAs) are part of deregulated insulin secretion in type 2 diabetes (T2D) development. Rodent models have suggested miR-200c to be involved, but the role and potential as therapeutic target of this miRNA in human islets is not clear. Here we report increased expression of miR-200c in islets from T2D… Read more

Published on 3 years ago

Source: Diabetes Journal

Distinct Characteristics between Perivascular and Subcutaneous Adipose Derived Stem Cells

Adipose derived stem cells (ADSCs) can differentiate into vascular lineages and participate in vascular remodeling. Perivascular ADSCs (PV-ADSCs) draw attention due to their unique location. The heterogeneity of subcutaneous (SUB-) and abdominal ADSCs were well addressed, but PV-ADSCs' heterogeneity hasn't been investigated. In the present study, we applied single-cell analysis… Read more

Published on 3 years ago

Source: Diabetes Journal

An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript

Fructosamine is a measure of short-term glycemic control, which has been suggested as a useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of diabetes. To date, a single genome-wide association study (GWAS) including 8,951 US White and 2,712 US Black individuals without a diabetes diagnosis has been… Read more

Published on 3 years ago

Source: Diabetes Journal

The Exercise-induced Improvement in Insulin-stimulated Glucose Uptake by Rat Skeletal Muscle Is Absent in Male AS160-Knockout Rats, Partially Restored by Muscle Expression of Phosphomutated AS160, and Fully Restored by Muscle Expression of Wildtype AS160

One exercise session can elevate insulin-stimulated glucose uptake (ISGU) in skeletal muscle, but the mechanisms remain elusive. Circumstantial evidence suggests a role for Akt substrate of 160 kDa (AS160 or TBC1D4). We used genetic approaches to rigorously test this idea. The initial experiment evaluated AS160's role for the postexercise increase… Read more

Published on 3 years ago

Source: Diabetes Journal