las

Welcome all seeking refuge from low carb dogma!

“To kill an error is as good a service as, and sometimes even better than, the establishing of a new truth or fact”
~ Charles Darwin (it's evolutionary baybeee!)

Saturday, July 24, 2010

Fat storage in pancreas and in insulin-sensitive tissues in pathogenesis of type 2 diabetes

Fat storage in pancreas and in insulin-sensitive tissues in pathogenesis of type 2 diabetes

Obesity is associated with increased storage of lipids in nonadipose tissues like skeletal muscle, liver, and pancreatic b 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 b 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 KATP channel activity, and uncoupling of the mitochondria. In addition, the saturated FFA palmitate increases cell death by apoptosis via increase in ceramide synthesis.
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In obesity, a situation of excess supply and/or decreased oxidation, fatty acid not only accumulate in adipose cells but also in other tissues like skeletal muscle, liver, and pancreatic b cells. Triglycerides are not harmful as such, but are precursors of signalling molecules like LC-CoA, diacylglycerol, ceramides, acting directly or indirectly in skeletal muscle on insulin signalling and glucose uptake, and in pancreatic b cells, on insulin secretion and cell viability. 

Going to leave this one just "out there" except to say that it ties in with a lot of the other research/studies I've been posting about lately.

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