Glucose intolerance in renal failure: role of endogenous opioids

Plasma concentrations of glucose, insulin, and beta-endorphin/beta-lipotropin were measured in male Sprague-Dawley rats with experimental renal failure after intravenous glucose challenge in the presence and absence of opioid blockade with intravenously administered naloxone. The results were compared with those obtained in sham-operated normal control and pair-fed groups of animals. Baseline glucose concentrations were similar in the three groups of animals. Plasma baseline insulin concentrations were significantly lower in the rats with renal failure and the pair-fed animals compared with the normal controls. After glucose challenge the renal failure group demonstrated glucose intolerance, which was not improved after naloxone treatment given 15 minutes before glucose challenge. Peak insulin levels after glucose challenge in the renal failure and pair-fed groups increased significantly after naloxone administration. Interestingly, circulating concentrations of plasma beta-endorphin/beta-lipotropin were not significantly different in the three groups of animals when measured either in the baseline state or after glucose challenge. The data indicate that the carbohydrate intolerance in experimental renal failure may be partly due to an increase in pancreatic islet opioidergic tone, because an improvement in insulin secretion was demonstrated in the absence of any change in circulating beta-endorphin/beta-lipotropin concentrations after naloxone. The failure to demonstrate any improvement in glucose disposal after naloxone, despite the augmented secretion of insulin after naloxone in the animals with renal failure, points to peripheral resistance to the effects of insulin that is not influenced by opioid blockade.(ABSTRACT TRUNCATED AT 250 WORDS)