Diabetologia

, Volume 36, Issue 12, pp 1221–1229

Metabolic origin of insulin resistance in obesity with and without Type 2 (non-insulin-dependent) diabetes mellitus

  • J. P. Felber
  • E. Haesler
  • E. Jéquier
Review

DOI: 10.1007/BF00400798

Cite this article as:
Felber, J.P., Haesler, E. & Jéquier, E. Diabetologia (1993) 36: 1221. doi:10.1007/BF00400798

Summary

A metabolic hypothesis is presented for insulin resistance in obesity, in the presence or absence of Type 2 (non-insulin-dependent) diabetes mellitus. It is based on physiological mechanisms including a series of negative feed-back mechanisms, with the inhibition of the function of the glycogen cycle in skeletal muscle as a consequence of decreased glucose utilization resulting from increased lipid oxidation in the obese. It considers the inhibition of glycogen synthase activity together with inhibition of glucose storage and impaired glucose tolerance. The prolonged duration of increased lipid oxidation, considered as the initial cause, may lead to Type 2 diabetes. This hypothesis is compatible with others based on the inhibition of insulin receptor kinase and of glucose transporter activities.

Key words

Insulin resistance lipid oxidation glycogen synthase glycogen phosphorylase glycogen cycle 

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • J. P. Felber
    • 1
  • E. Haesler
    • 1
  • E. Jéquier
    • 1
  1. 1.Institut de PhysiologieUniversité de LausanneLausanneSwitzerland