Diet- and diabetes-induced change in insulin binding to the nuclear membrane in spontaneously diabetic rats is associated with change in the fatty acid composition of phosphatidylinositol.

Insulin binding to the nucleus in vivo alters the binding of transcription factors to the promoter region of lipogenic genes, thereby changing expression of these genes. The present research was designed to investigate whether change in diet fat composition alters insulin binding to nuclear insulin receptors at various stages of onset of diabetes in spontaneously diabetic B/B rats. The fatty acid composition of lipids comprising the nuclear membrane was also examined. Weanling rats were fed a nonpurified diet (low-fat commercial rat chow) or a semipurified diet containing 20 g/100 g fat of either high (1.0) or low (0.25) polyunsaturated to saturated (P/S) fatty acid ratio. Insulin binding to liver nuclei was measured when the blood glucose level was 100 mg/dl and 400 mg/dl. No effect of diet treatment on age of onset of diabetes was found. Specific binding of insulin to nuclei from rats with a blood glucose level of 100 mg/dl did not differ from nondiabetic rats, and was higher than in diabetic rats with a blood glucose level of 400 mg/dl. Insulin binding was greater in rats fed a high P/S diet. The high versus low P/S diet treatment primarily altered the fatty acid composition of phosphatidylinositol in the nuclear membrane. Diabetic rats fed nonpurified diet showed a significant increase in levels of 18:2(n-6) and 22:6(n-3), whereas 20:4(n-6) decreased in the phosphatidylcholine fraction compared with control rats fed chow. As rats became diabetic, the level of monounsaturated fatty acids, 18:2(n-6) and 22:6(n-3) decreased, whereas the level of 20:4(n-6) increased in phosphatidylinositol. Change in the composition of these nuclear membrane components may be associated with transitions in insulin binding.