Journal
INTERNATIONAL JOURNAL OF OBESITY
Volume 28, Issue -, Pages S53-S57Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.ijo.0802857
Keywords
muscle; pancreatic beta cell; insulin secretion; insulin action; long-chain fatty acyl CoA; diacylglycerol; ceramide; protein kinase C
Categories
Ask authors/readers for more resources
Obesity is associated with increased storage of lipids in nonadipose tissues like skeletal muscle, liver, and pancreatic beta cells. These lipids constitute a continuous source of long-chain fatty acyl CoA (LC-CoA) and derived metabolites like diacylglycerol and ceramide, acting as signalling molecules on protein kinases activities ( in particular, the family of PKCs), ion channel, gene expression, and protein acylation. In skeletal muscle, the increase in LC-CoA and diacylglycerol translocates and activates specific protein kinase C (PKC) isoforms, which will phosphorylate IRS-1 on serine, preventing its phosphorylation on tyrosine and association with PI3 kinase. This interrupts the insulin signalling pathway leading to the stimulation of glucose transport. In pancreatic beta cells, short-term excess of fatty acids or LC-CoA activates PKC and also directly stimulates insulin exocytosis. Longterm exposure to free fatty acids (FFA) leads to an increased basal and blunted glucose-stimulated insulin secretion by affecting gene expression, increase in K-ATP channel activity, and uncoupling of the mitochondria. In addition, the saturated FFA palmitate increases cell death by apoptosis via increase in ceramide synthesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available