Imeglimin, a drug for type 2 diabetes, reportedly promotes β-cell proliferation and increases β-cell survival; however, the detailed underlying molecular mechanism remains unclear. Here, we investigated metabolites in pancreatic islets after imeglimin treatment via liquid chromatography with tandem mass spectrometry. Treatment with imeglimin for 1 h significantly altered the levels of 17 metabolites at 5.6 […]
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Lipidomic Signatures of Insulin Resistance Identified From Hyperinsulinemic-Euglycemic Clamp Studies in Asian Men
Insulin resistance (IR) is fundamental to the development of type 2 diabetes and usually precedes the disease by several years. Therefore, a better understanding of the molecular pathogenesis of IR may help better manage and prevent the metabolic syndrome. We used an integrated approach of anthropometric and biochemical measures in conjunction with serum lipidomics for […]
Read MoreImpacts of Metabolic Reprogramming on the Onset of Diabetic Nephropathy in Mice With Varying Lias Gene Expression Levels
Metabolic and energy reprogramming, potentially regulated by protein lipoylation, plays a critical role in maintaining kidney function and cell survival in diabetic kidney disease (DKD). However, it remains unclear whether improper reprogramming contributes to the onset of DKD. To investigate this issue, we developed a group of metabolic mouse models with varying levels of protein […]
Read MoreThe GLP-1 Receptor Agonist Dulaglutide Attenuates Hepatic Steatosis in Obesity via a Weight-Independent Mechanism
Recent clinical trials testing glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrated improved outcomes in obesity-associated complications, including cardiovascular events and hepatic steatosis. Despite their positive effects, whether the benefits of GLP-1 RAs are due to weight loss or are a direct therapeutic effect remains unclear. Therefore, we pair fed middle-aged low-density lipoprotein receptor knockout (Ldlr−/−) […]
Read MoreFuture Directions and Clinical Trial Considerations for Novel Islet β-Cell Replacement Therapies for Type 1 Diabetes
Type 1 diabetes results from the immune-mediated loss of insulin-producing pancreatic islet β-cells, rendering those affected dependent on exogenous insulin to survive. Despite the array of choices available for insulin delivery, treatment to maintain near-normal glucose metabolism while avoiding hypo- and hyperglycemia remains a challenge. After two decades of clinical trials across four continents, the […]
Read MoreThe Dorsal Raphe Nucleus and the Integrative Control of Feeding: A Report on Research Supported by Pathway to Stop Diabetes
Obesity is a major risk factor for the development of type 2 diabetes (T2D). While the connection between these two disease entities is still incompletely understood, even modest weight loss can greatly reduce the risk of developing T2D and its sequelae. With the recent success of antiobesity pharmacotherapies, which appear to exert their effects largely […]
Read MoreEmpagliflozin Enhances Hepatic Glucose Production and Reduces Total-Body Norepinephrine Turnover Rate: A Randomized Trial
The current study examined the effect of empagliflozin on hepatic glucose production (HGP) and total-body norepinephrine (NE) turnover in individuals with and without type 2 diabetes (T2D). The study randomized 36 individuals with T2D and 36 individuals without T2D to receive in a double-blind fashion empagliflozin or matching placebo (2:1 ratio) for 12 weeks. HGP […]
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Read MoreDiabetes Spotlight: David J. Hodson, BVSc, PhD, FRCVS—Regulation of Insulin and Glucagon in Pancreatic Islet Biology
In the Pennines, a range of moorland hills in northern England, it rains for much of the year. “The grass grows very green, very long, and as a consequence, the cows produce a lot of milk,” David Hodson says. As a kid growing up in this farmland outside of Manchester, Hodson always saw the livestock […]
Read MoreDNA Methylation Biomarkers Predict Offspring Metabolic Risk From Mothers With Hyperglycemia in Pregnancy
Gestational diabetes mellitus affects almost 18 million pregnancies worldwide, increasing by >70% in the past 20 years. DNA methylation has been associated with maternal hyperglycemia and type 2 diabetes risk in offspring. This study hypothesized that hyperglycemia during pregnancy influences DNA methylation changes at birth that mediate metabolic risk in offspring. Cord blood samples (n […]
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