High Plasma Free Fatty Acid Levels Contribute to the Hypersomatostatinemia of Insulin Deficiency

High plasma levels of free fatty acids (FFA) stimulate the secretion of splanchnic somatostatin, and both are elevated in insulin deficiency. To determine if the hypersomatostatinemia of insulin deficiency is secondary to high FFA levels, plasma somatostatin-like immunoreactivity (SLI) was measured in a group of insulin- deprived alloxan-diabetic dogs during nicotinic acid-induced lowering of their elevated plasma FFA to normal, and in a group of nondiabetic dogs during nicotinic acid-induced lowering of their FFA to subnormal values. In insulin-deprived diabetic dogs, nicotinic acid reduced plasma FFA from 1.07 ± 0.2 (M ± SE) mmol/L to 0.6 ± 0.1 mmol/L (P < 0.02), approximately the basal FFA level in normal dogs. This was accompanied by a significant decline in plasma SLI levels from a mean baseline of 247 ±15 pg/ml to a mean nadir of 199 ± 10 pg/ml (P < 0.005). The latter was, nevertheless, significantly above the basal SLI level of the nondiabetic dogs. In contrast, in normal dogs, nicotinic acid-induced reduction in FFA from 0.54 ± 0.02 mmol/L to 0.24 ± 0.03 mmol/ (P < 0.001) was associated with only a small and inconsistent decrease in SLI. These findings suggest that the hypersomatostatinemia of insulin-deficient alloxan-diabetic dogs is, in part, secondary to high plasma FFA levels.