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- Title
Effect of d-fenfluramine on basal glucose turnover and fat-feeding-induced insulin resistance in rats.
- Authors
Storlien, Leonard H.; Thorburn, Anne W.; Smythe, George A.; Jenkins, Arthur B.; Chisholm, Donald J.; Kraegen, Edward W.; Storlien, L H; Thorburn, A W; Smythe, G A; Jenkins, A B; Chisholm, D J; Kraegen, E W
- Abstract
There is evidence that fenfluramine improves insulin action independently of its anorectic and weight-loss-inducing properties. Chronic d-fenfluramine also reduces hypothalamic noradrenergic tone, which correlates highly with hepatic glucose output. We report that chronic d-fenfluramine (5 mg.kg-1.day-1) ameliorates insulin resistance induced by high-fat feeding. Insulin action was assessed in adult male rats at basal insulin levels and at hyperinsulinemia (approximately 140 mU/L with the euglycemic clamp technique). Hepatic glucose production, peripheral glucose disposal, and individual tissue glucose metabolism were determined from bolus injections of [3H]-2-deoxyglucose and [14C]glucose. Food intake was matched between groups. Basal glucose turnover was reduced 28% (P less than .05) in fat-fed rats receiving d-fenfluramine (fat + fen). The glucose infusion rate to maintain euglycemia was 22.0 +/- 1.1 mg.kg-1.min-1 in the high-carbohydrate-fed rats, 8.2 +/- 1.0 in fat-fed rats, and 15.1 +/- 0.5 in the fat + fen group. Peripheral glucose disposal, reflecting measured skeletal muscle changes, was reduced by fat feeding (from 23.5 +/- 1.0 to 13.8 +/- 0.6 mg.kg-1.min-1) but was improved by d-fenfluramine (16.9 +/- 0.5, P less than .05 vs. fat fed). Impaired suppression of hepatic glucose output by insulin, caused by fat feeding, was totally reversed by d-fenfluramine. Thus, d-fenfluramine counteracted diet-induced insulin resistance, with the predominant effect on the liver. We hypothesize that d-fenfluramine improves insulin action by reducing hypothalamic noradrenergic tone, which in turn reduces the neural drive to hepatic glucose output and improves the hepatic response to insulin.
- Publication
Diabetes, 1989, Vol 38, Issue 4, p499
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diab.38.4.499