Insulin resistance diacylglycerol

Itani SI, Ruderman NB, Schmieder F and Boden G. 2002. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 51(7) 2005-2011. 

PKC0 also activates IkB kinase and c-Jun N-terminal kinase in adipocytes. Both of these protein kinases have been shown to phosphorylate a serine residue of IRS-1. In contrast to PKC0, PKC5 leads to phosphorylation of p47, activating NADPH oxidase. These molecular mechanisms that result from increased diacylglycerol accumulation in adipocytes may at least in part, explain the insulin resistance associated with obesity. 

Recent studies in humans and animal models have revealed that modulation of stearoyl-CoA desaturase-1 (SCDl) activity by dietary intervention or genetic manipulation strongly influences several facets of energy metabolism to affect the susceptibility to obesity, insulin resistance, diabetes and hyperlipidaemia (Flowers and Ntambi, 2008, 2009 Paton and Ntambi, 2008). SCDl catalyzes the DO-di desaturation of a range of fatty acyl-CoA substrates. The preferred substrate is stearoyl-CoA, which produces OA from stearic acid (18 0). The major product of SCDl, OA (18 ln-9), is the key substrate for the formation of complex lipids such as phospholipids, TAG, cholesterol esters, wax esters and alkyl-2,3-diacylglycerols. Reduced OA synthesis is associated with several metabolic changes that elicit protection from obesity, cellular Upid accumulation and insulin resistance (Miyazaki et al., 2000 Ntambi et al., 2002 Sampath et al., 2007). 

---