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Abnormal glucose homeostasis due to chronic hyperresistinemia.

Resistin is an adipocyte-secreted protein that circulates at increased levels in obesity. Acute administration of resistin impairs glucose tolerance, but the effects of chronic hyperresistinemia have not been established. Here we describe the generation and characterization of transgenic mice that have high circulating levels of resistin in the setting of normal weight. Fasted blood glucose was higher in resistin-transgenic mice than in their nontransgenic littermates, and glucose tolerance was impaired in the hyperresistinemic mice. Metabolic studies in the setting of a hyperinsulinemic-euglycemic clamp protocol revealed that chronically hyperresistinemic mice have elevated glucose production. This increase in glucose production may be partly explained by increased expression of hepatic phosphoenolpyruvate carboxykinase. Thus, chronic hyperresistinemia impairs normal glucose metabolism.

Pubmed ID: 15189975

Authors

  • Rangwala SM
  • Rich AS
  • Rhoades B
  • Shapiro JS
  • Obici S
  • Rossetti L
  • Lazar MA

Journal

Diabetes

Publication Data

August 27, 2004

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK45024
  • Agency: NIDDK NIH HHS, Id: DK48321
  • Agency: NIDDK NIH HHS, Id: DK49210
  • Agency: NIDDK NIH HHS, Id: DK49780
  • Agency: NIDDK NIH HHS, Id: P01 DK49210
  • Agency: NIDDK NIH HHS, Id: P30 DK19525
  • Agency: NIDDK NIH HHS, Id: P60 DK20541

Mesh Terms

  • Animals
  • Blood Glucose
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Homeostasis
  • Hormones, Ectopic
  • Hyperinsulinism
  • Insulin
  • Liver
  • Mice
  • Mice, Transgenic
  • Phosphoenolpyruvate Carboxykinase (ATP)
  • Prealbumin
  • Resistin