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Glucagon-like Peptide-1 Protects Pancreatic Beta-cells from Death by Increasing Autophagic Flux and Restoring Lysosomal Function

Studies in animal models of type 2 diabetes have shown that glucagon-like peptide-1 (GLP-1) receptor agonists prevent β-cell loss. Whether GLP-1 mediates β-cell survival via the key lysosomal-mediated process of autophagy is unknown.

Here we report that treatment of INS-1E β-...

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Hyperglycemia-induced Changes in ZIP7 and ZnT7 Expression Cause Zn2+ Release from the Sarco(endo)plasmic Reticulum and Mediate ER-stress in the Heart

Changes in cellular free Zn2+ concentration, including those in the sarco(endo)plasmic reticulum [S(E)R], are primarily coordinated by Zn2+-transporters whose identity and role in the heart is not well established. Here, we hypothesized that ZIP7 and ZnT7 transport Zn2+...

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Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamic, in Insulin Resistant Obese Mice

Fatty liver, oxidative stress, and mitochondrial dysfunction are key pathophysiological features of insulin resistance and obesity. Butyrate, produced by fermentation in the large intestine by gut microbiota, and its synthetic derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide, FBA, have b...

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Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet {alpha}-Cells into {beta}-Cells in Vivo

Among the therapeutic avenues being explored for replacement of the functional islet β-cell mass lost in Type 1 diabetes (T1D), reprogramming of adult cell types into new β-cells has been actively pursued. Notably, mouse islet α-cells will transdifferentiate into β-cells unde...

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An ATF4/ATG5 Signaling in Hypothalamic POMC Neurons Regulates Fat Mass via Affecting Energy Expenditure

Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. Here, we showed that hypothalamic pro-opiomelanocortin (POMC) neurons specific ATF4 knockout (PAKO) mice a...

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Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice

Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)...

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Identification and Functional Implications of Sodium/Myo-inositol Cotransporter 1 in Pancreatic Beta-cells and Type 2 Diabetes Mellitus

Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (...

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Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy

Impaired rate dependent depression (RDD) of the Hoffman-reflex is associated with reduced dorsal spinal cord potassium chloride co-transporter expression and impaired spinal GABAA receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of i...

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