Background/aims: β-Cell apoptosis caused by increased endoplasmic reticulum (ER) stress is an important pathogenic component of type 2 diabetes mellitus. In theory, sulfonylureas, used for the treatment of diabetes, can contribute to ER stress. We assessed changes in ER stress in pancreatic β-cells under glucotoxic or glucolipotoxic conditions using low concentrations of the sulfonylurea, glibenclamide (GB).
Methods: Low concentrations of GB (10 or 100 nM) were added to INS-1 cells cultured under glucotoxic or glucolipotoxic conditions. The degree of viability, level of apoptosis and levels of markers associated with ER stress were measured.
Results: Apoptosis decreased in response to low concentrations of GB under glucolipotoxic but not glucotoxic conditions. Most ER stress markers decreased upon the addition of GB. Under glucotoxic conditions, changes in the levels of ER stress markers were not consistent. However, all decreased significantly under glucolipotoxic conditions.
Conclusions: Low concentrations of GB exerted antiapoptotic effects through the attenuation of ER stress under glucolipotoxic conditions.
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http://dx.doi.org/10.3904/kjim.2013.28.3.339 | DOI Listing |
Cell Mol Life Sci
January 2025
Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung City, 402, Taiwan.
Background: Diabetes is a primary contributor to diabetic cardiomyopathy (DbCM), which is marked by metabolic imbalances such as elevated blood glucose and lipid levels, leading to significant structural and functional alterations in the myocardium. Elevated free fatty acids (FFAs) and hyperglycemia play critical roles in DbCM development, with FFAs inducing insulin resistance in cardiomyocytes and promoting lipid accumulation, resulting in oxidative stress and fibrosis. Current research suggests that glucagon-like peptide-1 (GLP-1) receptor agonists may effectively mitigate DbCM, although an effective treatment for this condition remains elusive, and the precise mechanisms of this protective effect are not fully understood.
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January 2025
Immuno-Endocrinology, Diabetes & Metabolism Laboratory, Instituto de Investigaciones en Medicina Traslacional (IIMT), CONICET - Universidad Austral, Pilar, Argentina; Facultad de Ciencias Biomédicas, , Universidad Austral, Pilar, Argentina. Electronic address:
Aims: Type 2 diabetes (T2D) is a prevalent metabolic disease linked to obesity and metabolic syndrome (MS). The glucolipotoxic environment (GLT) impacts tissues causing low-grade inflammation, insulin resistance and the gradual loss of pancreatic β-cell function, leading to hyperglycemia. We have previously shown that Compound A (CpdA), a plant-derived dissociative glucocorticoid receptor-modulator with inflammation-suppressive activity, displays protective effects on β-cells in type 1 diabetes murine models.
View Article and Find Full Text PDFKnockdown (KD) of lipid droplet (LD) protein perilipin 2 (PLIN2) in beta cells impairs glucose-stimulated insulin secretion (GSIS) and mitochondrial function. Here, we addressed a pathway responsible for compromised mitochondrial integrity in PLIN2 KD beta cells. In PLIN2 KD human islets, mitochondria were fragmented in beta cells but not in alpha cells.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
December 2024
Department of Biochemistry, Periyar University, Salem, India.
Glucolipotoxicity (GLT) has emerged as established mechanism in the progression of diabetes. Identifying compounds that mitigate GLT-induced deleterious effect on β-cells are considered important strategy to overcome diabetes. Hence, in the present study, astaxanthin-s-allyl cysteine (AST-SAC) diester was studied against GLT in β-cells.
View Article and Find Full Text PDFObes Rev
November 2024
School of Pharmaceutical Sciences, Wenzhou Medical University, & Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Wenzhou, Zhejiang, China.
Metabolic dysfunction-associated steatohepatitis (MASH) is a condition characterized by hepatosteatosis, inflammation, and tissue damage, with steatosis as the initial stage, which involves chronic, excess deposition of lipids in hepatic lipid droplets. Despite the growing prevalence and serious risks it poses, including liver decompensation, the need for transplantation, and increased patient mortality, MASH currently faces no approved pharmacotherapy. Several promising treatment candidates have emerged from recent clinical trials, including analogs of FGF21 and agonists of the associated FGFR1-KLB complex.
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