General Information:

Id: 3,659 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mammalia
review
Reference: Prentki M and Madiraju SR(2012) Glycerolipid/free fatty acid cycle and islet beta-cell function in health, obesity and diabetes Mol. Cell. Endocrinol. 353: 88-100 [PMID: 22108437]

Interaction Information:

Comment The importance of long-chain acylcoenzyme A synthase activity in insulin secretion became evident as long-chain acyl-coenzyme A synthase inhibitor, triacsin-C, strongly obliterated the FFA-augmented glucose-stimulated insulin secretion (GSIS) in rat islets.
Formal Description
Interaction-ID: 34896

gene/protein

ACSL

affects_activity of

in pancreas, in pancreatic beta cells
Comment Enhancing the expression of GPAT-1 in the beta-cell does not alter GSIS, suggesting no direct relation between this isoenzyme, LPA levels and insulin secretion. This is consistent with previous work that showed no effect of exogenous LPA on insulin secretion in isolated rat islets, although lysophatidylinositol was effective.
Formal Description
Interaction-ID: 34911

gene/protein

GPAM

NOT affects_activity of

Comment Enhancing the expression of GPAT-1 in the beta-cell does not alter GSIS, suggesting no direct relation between this isoenzyme, LPA levels and insulin secretion. This is consistent with previous work that showed no effect of exogenous LPA on insulin secretion in isolated rat islets, although lysophatidylinositol was effective.
Formal Description
Interaction-ID: 34913
Comment The final step of lipogenesis is the synthesis of TG from DAG, catalyzed by DGAT-1 and DGAT-2. Both of these enzymes are present on the ER and also on lipid droplets. DGAT-1-KO mice were shown to have increased insulin sensitivity and enhanced glucose tolerance and are resistant to diet-induced obesity. Overexpression of DGAT-1 in rat islet cells has been shown to enhance TG synthesis and to cause decreased GSIS, supporting the view that DAG or its derivatives is implicated in insulin secretion.
Formal Description
Interaction-ID: 34929
Comment Besides HSL, DAG can also be hydrolyzed by the plasma membrane associated sn1-DAG lipases alpha and beta, which are different gene products. Inhibition of islet DAG hydrolysis by the DAGL inhibitor RHC80267 decreases GSIS.
Formal Description
Interaction-ID: 34930
Comment Besides HSL, DAG can also be hydrolyzed by the plasma membrane associated sn1-DAG lipases alpha and beta, which are different gene products. Inhibition of islet DAG hydrolysis by the DAGL inhibitor RHC80267 decreases GSIS.
Formal Description
Interaction-ID: 34984
Comment Phospholipase-D-generated phosphatidic acid (PA) is important in GSIS at the exocytotic step, but it is uncertain whether PA derived from lipogenesis is implicated in this process.
Formal Description
Interaction-ID: 34996

drug/chemical compound

Phosphatidate

affects_activity of

if PA is phospholipase-D-generated
Comment Hydrolysis of PA by lipins produces sn1,2-DAG, which is known to bind with the C1-domains of many proteins involved in the insulin secretory pathway, including the priming exocytotic effector Munc13-1, protein kinase C enzymes, and protein kinase D. Munc13-1 is a vesicle priming effector activated by DAG and the evidence indicates similar function in the beta-cell. Lowered Munc13-1 expression results in reduced circulating insulin levels, glucose intolerance and curtailed GSIS in isolated mouse islets. Thus, it has been proposed that DAG-mediated activation of Munc13-1 provides a link between glucose-induced lipolysis in the beta-cell and the amplification arm of fuel induced insulin secretion.
Formal Description
Interaction-ID: 35003