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Hypoxia in Combination With Muscle Contraction Improves Insulin Action and Glucose Metabolism in Human Skeletal Muscle via the HIF-1{alpha} Pathway

Skeletal muscle insulin resistance is the hallmark of type 2 diabetes, and develops long before the onset of the disease. It is well accepted that physical activity improves glycemic control but the knowledge on underlying mechanisms mediating the beneficial effects remains incomplete. Exercise i...

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Long-term Hyperglycemia Naturally Induces Dental Caries But Not Periodontal Disease in Type-1 and Type-2 Diabetic Rodents

Periodontal disease (PD) in diabetic patients is described as the 6th complication of diabetes. We have previously shown that diabetes increases dental caries, and carious inflammation might have a strong effect on the adjacent periodontal tissue in diabetic rodent models. However, the possibilit...

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DDB1-mediated CRY1 Degradation Promotes FOXO1-driven Gluconeogenesis in Liver

Targeted protein degradation through ubiquitination is an important step in the regulation of glucose metabolism. Here we present evidence that the DDB1-CUL4A ubiquitin E3 ligase functions as a novel metabolic regulator that promotes FOXO1-driven hepatic gluconeogenesis. In vivo, hepatocyte-speci...

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SMAD3/Stat3 Signaling Mediates {beta}-Cell Epithelial-Mesenchymal Transition in Chronic Pancreatitis-Related Diabetes

Many patients with chronic pancreatitis develop diabetes (chronic pancreatitis-related diabetes; CPRD) through an undetermined mechanism. Here, we used long-term partial pancreatic duct ligation (PDL) as a model to study CPRD. We found that long-term PDL induced significant β-cell dedifferen...

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Opposite Regulation of Insulin Sensitivity by Dietary Lipid Versus Carbohydrate Excess

To understand the mechanisms in lipid-induced insulin resistance, a more physiologic approach is to enhance FA availability through the diet. Nine healthy men ingested two hypercaloric diets (+75 E%) for three days, enriched in unsaturated FA (78 E% fat; UNSAT) or carbohydrates (80 E% carbohydrat...

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Structural Basis and Genotype-phenotype Correlations of INSR Mutations Causing Severe Insulin Resistance

The insulin receptor (INSR) gene was analyzed in four patients with severe insulin resistance, revealing 5 novel mutations and a deletion that removed exon 2. A patient with Donohue syndrome (DS) had a novel p.V657F mutation in the second fibronectin type III domain (FnIII-2), which contai...

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NADPH Oxidase-Nox5 Accelerates Renal Injury in Diabetic Nephropathy

NADPH-oxidase derived excessive production of reactive oxygen species (ROS) in the kidney plays a key role in mediating renal injury in diabetes. Pathological changes in diabetes include mesangial expansion and accumulation of extracellular matrix (ECM) leading to glomerulosclerosis. There is a p...

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