Author/Editor     Hevener, Andrea; Reichart, Donna; Janež, Andrej; Olefsky, Jerrold
Title     Female rats do not exhibit free fatty acid-induced insulin resistance
Type     članek
Source     Diabetes
Vol. and No.     Letnik 51, št. 6
Publication year     2002
Volume     str. 1907-12
Language     eng
Abstract     It is well described that excessive lipid metabolism can cause insulin resistance in both animals and humans, and this has been implicated as a causative factor in the development of insulin resistance and type 2 diabetes in humans. Recently, we have shown that intravenous lipid emulsion (liposyn) infusion during a 120-min euglycemic-hyperinsulinemic clamp led to significant reductions in insulin action and fatty acid translocase (FAT/CD36) skeletal muscle protein expression. After reviewing the literature, it became evident that essentially all past studies, including our own, were conducted in male animals. Therefore, to determine whether there were sex determinants of fat-induced insulin resistance, we assessed the impact of free fatty acid (FFA) elevation on insulin action in female rats. Here, we report that a fourfold elevation in plasma FFA concentration induced a 40% reduction in the insulin-stimulated glucose disposal rate, a 30% decline in insulin-stimulated skeletal muscle insulin substrate receptor-1 (IRS-1) phosphorylation, a 48% decrease in IRS-1-associated phosphatidylinositol (PI) 3-kinase activity, and a 50% reduction in muscle FAT/CD36 protein expression in male rats. In striking contrast, we found no effect of FFA elevation to cause insulin resistance, changes in IRS-1/PI 3-kinase, or FAT/CD36 protein levels in female animals. Our findings indicate that female animals are protected from lipid-induced reductions in insulin action.
Descriptors     INSULIN RESISTANCE
FATTY ACIDS, NONESTERIFIED
BLOOD GLUCOSE
FAT EMULSIONS, INTRAVENOUS
GLUCOSE CLAMP TECHNIQUE
INSULIN
KINETICS
MUSCLE, SKELETAL
PHOSPHOPROTEINS
PHOSPHORYLATION
PHOSPHOTYROSINE
RATS, WISTAR