Adipose-derived resistin and gut-derived resistin-like molecule–β selectively impair insulin action on glucose production
Michael W. Rajala, … , Philipp E. Scherer, Luciano Rossetti
Michael W. Rajala, … , Philipp E. Scherer, Luciano Rossetti
Published January 15, 2003
Citation Information: J Clin Invest. 2003;111(2):225-230. https://doi.org/10.1172/JCI16521.
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Categories: Article Metabolism

Adipose-derived resistin and gut-derived resistin-like molecule–β selectively impair insulin action on glucose production

Abstract

The adipose-derived hormone resistin is postulated to link obesity to insulin resistance and diabetes. Here, the infusion of either resistin or the resistin-like molecule–β (RELMβ) rapidly induced severe hepatic but not peripheral insulin resistance. In the presence of physiologic hyperinsulinemia, the infusion of purified recombinant resistin, increasing circulating resistin levels by approximately twofold to 15-fold, inhibited glucose metabolism such that lower rates of glucose infusion were required to maintain the plasma glucose concentration at basal levels. The effects of resistin and RELMβ on in vivo insulin action were completely accounted for by a marked increase in the rate of glucose production. These results support the notion that a novel family of fat- and gut-derived circulating proteins modulates hepatic insulin action.

Authors

Michael W. Rajala, Silvana Obici, Philipp E. Scherer, Luciano Rossetti

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Figure 3

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Effect of resistin and RELMβ on glucose disposal and production during i...
Effect of resistin and RELMβ on glucose disposal and production during insulin clamp studies. The measurements were obtained while plasma glucose concentration was maintained at approximately 7 mM under steady-state conditions. (a) Effect of resistin and RELMβ on the rate of glucose infusion (GIR; mg/kg/min). (b) Effect of resistin and RELMβ on the rate of glucose disappearance (Rd; mg/kg/min). (c) Effect of resistin and RELMβ on the rate of glucose production (GP; mg/kg/min). (d) Effect of resistin and RELMβ on hepatic insulin sensitivity (HIS; μU/ml). To take into account differences between animals in circulating plasma insulin levels during the insulin clamp studies, the same index of hepatic insulin sensitivity described in the Figure 2c legend was used. *P < 0.05 vs. vehicle.