ECE2019 Guided Posters Metabolic Syndrome and Hypoglycaemia (11 abstracts)
Beta cell senescence: effect of glucotoxicity and glucolipotoxicity
Mi-kyung Kim 1, , Hye Sook Jung 2 , Jeong Eun Jang 1 , Tae Nyun Kim 1 , Min Jeong Kwon 1 , Soon Hee Lee 1 , Byung Doo Rhee 1 & Jeong Hyun Park 1,
1Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; 2Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea.
Pancreatic beta cell senescence is one of the recent explanations for theincreased prevalence of type 2 diabetes in the elderly. Aging may exert a distinct influence on pancreatic β cell turnover, regeneration capacity and function. Oxidative stresses induced by metabolic stresses reduce pancreatic beta cell mass and secretion. We investigated how metabolic stresses effect on pancreatic beta cell senescence. INS-1 cells were exposed to 33mM glucose (glucotoxicity: high glucose (HG)) or 33 mM glucose with palmitate 200 uM (glucolipotoxicity: HG+palmitate (HGP)). Cell viability and apoptosis were assessed by MTT assay and Annexin V staining. We compared senescence β-Galactosidase (SA-β-Gal) staining and p16INK4aimmunostaining between high glucose (HG) and HG+palmitate (HGP). We assessed phospho-p38 MAPK, Sirt1 and p16 protein expression with metabolic stresses. CDK4 protein and antioxidant enzyme were assessed in both conditions. INS-1 cell viability was decreased and apoptosis was increased in both HG and HGP. SA-β-Gal and p16INK4a immunostaining were significantly increased in both stresses compared to control. HG and HGP decreased phospho-p38 MAPK and increased p16INK4aprotein expression. HG and HGP decreased CDK4 and catalase expression. In conclusion, we found metabolic stresses like glucotoxicity and glucolipotoxicity increased beta cell senescence. Beta cell aging induced metabolic stress may related to phospho-p38 MAPK and p16INK4apathway, beta cell cycle and anti-oxidant system.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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