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. DIABETES 17:353-61, June, 1968. It has been known for several years that plasma free fatty acid (FFA) levels are elevated in diabetes mellitus, 1>2 and this has been found to be due to accelerated mobilization of fatty acids from adipose tissue.

Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

“…In previous studies, nicotinic acid has been shown to both increase and decrease plasma glucose concentration in normal and diabetic humans and animals (7,(66)(67)(68)(69)(70)(71)(72)(73)(74). The reason for these discrepancies is not clear.…”

Additive Hypoglycemic Effects of Drugs That Modify Free-Fatty Acid Metabolism by Different Mechanisms in Rats With Streptozocin-Induced Diabetes

“…Diabetes 37: [28][29][30][31][32]1988 T he acute administration of either nicotinic acid (NA) or phenylisopropyladenosine (PIA), two potent antilipolytic agents, has been shown to lower elevated plasma free-fatty acid (FFA) concentrations in a rat model of non-insulin-dependent diabetes mellitus (NIDDM) (1). The fall in plasma FFA concentration was accompanied by a decrease in plasma triglyceride (TG) concentration, secondary to a reduction in very-low-density lipoprotein (VLDL)-TG secretion rate (1).…”

Effect of nicotinic acid-induced insulin resistance on pancreatic B cell function in normal and streptozocin-treated baboons.

“…Nicotinic acid (NA), the B group vitamin used in long-term treatment of some of the hyperlipidemic syndromes, fulfills these requirements. Acutely (within a few hours) NA lowers plasma free fatty acid levels (6-9) resulting in improved insulin action (10)(11)(12). However, during prolonged administration of NA (several days) free fatty acid levels are increased (13).…”