Sensitivity to Growth Hormone

Sensitivity to Growth Hormone

Insulin Resistance and Insulin Sensitizers
Michael Stumvoll, Hans Häring

Medizinische Klinik, Abteilung für Endokrinologie, Stoffwechsel und Pathobiochemie, Eberhard-Karls-Universität, Tübingen, Germany

Address of Corresponding Author

Horm Res 2001;55:3-13 (DOI: 10.1159/000063466)

  Key Words

• Insulin
• Insulin resistance
• Insulin sensitizers
• Genetic factors
• Type 2 diabetes mellitus
• Glucose intolerance
• Glucose disposal
• Obesity

  Abstract

Insulin resistance is a key factor in the pathogenesis of type 2 diabetes mellitus and a co-factor in the development of dyslipidaemia, hypertension and atherosclerosis. The causes of insulin resistance include factors such as obesity and physical inactivity, and there may also be genetic factors. The mechanism of obesity-related insulin resistance involves the release of factors from adipocytes which exert a negative effect on glucose metabolism: free fatty acids, tumour necrosis factor- and the recently discovered hormone, resistin. The two resulting abnormalities observed consistently in glucose-intolerant states are impaired suppression of endogenous glucose production, and impaired stimulation of glucose uptake. Among the genetic factors, a polymorphism (Pro12Ala) in the peroxisome proliferator-activated receptor (PPAR) is associated with a reduced risk of type 2 diabetes mellitus and increased insulin sensitivity, primarily that of lipolysis. On the other hand, the association with insulin resistance of a common polymorphism (Gly972Arg) in the insulin receptor substrate 1, long believed to be a plausible candidate gene, is weak at best. This polymorphism may instead be associated with reduced insulin secretion, which, in view of the recent recognition of the insulin signalling system in -cells, results in the development of a novel pathogenic concept. Finally, fine-mapping and positional cloning of the susceptibility locus on chromosome 2 resulted in the identification of a polymorphism (UCSNP-43 G/A) in the calpain-10 gene. In non-diabetic Pima Indians, this polymorphism was associated with insulin resistance of glucose disposal. The pharmacological treatment of insulin resistance has recently acquired a novel class of agents: the thiazolidinediones. They act through regulation of PPAR-dependent genes and probably interfere favourably with factors released from adipocytes which mediate obesity-associated insulin resistance.

Copyright © 2001 S. Karger AG, Basel

  Author Contacts

Prof. Dr. H. Häring
Medizinische Universitätsklinik, Otfried-Müller-Strasse 10
D-72076 Tübingen (Germany)
Tel. +49 7071 2980390, Fax +49 7071 292784
E-Mail michael.stumvoll@med.uni-tuebingen.de

  Article Information

Number of Print Pages : 11
Number of Figures : 5, Number of Tables : 1, Number of References : 106