Metabolic Effects of Nicotinic Acid in Acute Insulin Deficiency in the Rat

Abstract

To investigate the role of increased free fatty acid (FFA) mobilization in the hyperglycemia, ketonemia, hyperlipemia and fatty liver produced by acute insulin deficiency, nicotinic acid was used to inhibit FFA mobilization in rats given guinea pig anti-insulin serum (AIS). Effects on concentration of plasma FFA, blood glucose and betahydroxybutyric acid (BHBA), and plasma and liver lipids were studied acutely after nicotinic acid administration and during six and twenty-four hours of treatment with this compound. Nicotinic acid produced an immediate fall in plasma FFA and a lesser but significant decrease in blood glucose when given two hours after AIS. When treatment was begun simultaneously with administration of AIS and repeated every four hours, plasma FFA and plasma and liver lipids were kept at normal control levels or lower for at least six hours, and blood BHBA for eighteen hours. Blood glucose remained at 70 per cent of values in untreated rats for eighteen hours, yet exceeded control levels during this time. At twenty-four hours there were no important differences between treated and untreated animals in any parameter except plasma triglycerides. This change was possibly related to a rebound of FFA levels in the nicotinic acid treated group. The effects of nicotinic acid on plasma FFA, blood BHBA and plasma and liver lipids are most likely due to inhibition of FFA release from adipose tissue. Increased FFA mobilization in acute insulin deficiency could thus explain the increase in concentration of these substances during the first several hours after AIS administration. The mechanism of action of nicotinic acid and the influence of plasma FFA levels on glucose concentration is less clear.