Open AccessRestoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells
Author(s) -
Suman Asalla,
Shravan Babu Girada,
Ramya S. Kuna,
Debabrata Chowdhury,
Bhaskar Kandagatla,
Srinivas Oruganti,
Utpal Bhadra,
Manika Pal Bhadra,
Shasi V. Kalivendi,
Swetha Pavani Rao,
Anupama T. Row,
Ahamed Ibrahim,
Partha Pratim Ghosh,
Prasenjit Mitra
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep27513
Subject(s) - medicine , endocrinology , cholesterol , insulin , hyperinsulinemia , pancreatic islets , reverse cholesterol transport , secretion , diabetes mellitus , chemistry , biology , lipoprotein , insulin resistance , islet
Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation.