Unknown

Dataset Information

0

Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity.


ABSTRACT: BACKGROUND: In the progression towards diabetes, glucolipotoxicity is one of the main causes of pancreatic beta cell pathology. The aim of this study was to examine the in vitro effects of chronic glucolipotoxic conditions on cellular responses in pancreatic islets, including glucose and fat metabolism, Calcium mobilization, insulin secretion and insulin content. RESULTS: Exposure of islets to chronic glucolipotoxic conditions decreased glucose stimulated insulin secretion in vitro. Reduced protein levels of Glut2/slc2a2, and decreased glucokinase and pyruvate carboxylase mRNA levels indicated a significant lowering in glucose sensing. Concomitantly, both fatty acid uptake and triglyceride accumulation increased significantly while fatty acid oxidation decreased. This general suppression in glucose metabolism correlated well with a decrease in mitochondrial number and activity, reduction in cellular ATP content and dampening of the TCA cycle. Further, we also observed a decrease in IP3 levels and lower Calcium mobilization in response to glucose. Importantly, chronic glucolipotoxic conditions in vitro decreased insulin gene expression, insulin content, insulin granule docking (to the plasma membrane) and insulin secretion. CONCLUSIONS: Our results present an integrated view of the effects of chronic glucolipotoxic conditions on known and novel signaling events, in vitro, that results in reduced glucose responsiveness and insulin secretion.

SUBMITTER: Somesh BP 

PROVIDER: S-EPMC3704974 | BioStudies | 2013-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3668190 | BioStudies
2010-01-01 | S-EPMC2947580 | BioStudies
1985-01-01 | S-EPMC1145042 | BioStudies
2016-01-01 | S-EPMC4855919 | BioStudies
2017-01-01 | S-EPMC5690378 | BioStudies
1000-01-01 | S-EPMC5645413 | BioStudies
2013-01-01 | S-EPMC3546920 | BioStudies
2013-01-01 | S-EPMC3717389 | BioStudies
2008-01-01 | S-EPMC2583206 | BioStudies
2008-01-01 | S-EPMC2164968 | BioStudies