Comparative effects of palmitic acid and ω‐3 PUFA on insulin regulation of glucose metabolism in rat skeletal muscle

Abstract

The effect of palmitic and ω‐3 polyunsaturated fatty acids (PUFA) on glucose metabolism stimulated by insulin in incubated rat soleus muscle was compared. The effect of palmitic acid on insulin signaling was also examined. Rat soleus muscles were incubated in the presence of palmitic, α‐linolenic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids (800 or 400 μM) for 5 hours in the presence of insulin (100 or 10000 μUI). 2‐Deoxi‐[2,6‐3H]‐D‐glucose (2‐d‐G) uptake, [14C]‐glycogen synthesis and [U‐14C]‐D‐glucose oxidation were measured. Tyrosine phosphorylation of insulin receptor substrate 1/2 (IRS 1/2), protein kinase B (AKT), glycogen synthase kinase 3 (GSK‐3) and MAP kinases p44 e p42 was evaluated. Palmitic acid inhibited the increase in 2‐d‐G uptake, glucose oxidation and [14C]‐glycogen synthesis stimulated by insulin. The two last effects were also induced by α‐linolenic acid. Palmitate effects were preceded by a reduction in the phosphorylation state of IRS‐1/2 (30%), AKT (51%), GSK‐3 (33%) and MAP kinases p44 e p42 (88%). Palmitate induced insulin resistance in 5h‐incubated soleus muscle. It was noteworthy that EPA and DHA did not impair glucose metabolism. The divergent effects of DHA and EPA with that of α‐linolenic acid indicates that the effects of a specific FA are not necessary mimicked by all FA of the same family. Financial Support: FAPESP, CNPq and CAPES.