Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro

Nature. 1988 Oct 13;335(6191):632-5. doi: 10.1038/335632a0.


Insulin resistance occurs in a variety of conditions, including diabetes, obesity and essential hypertension, but its underlying molecular mechanisms are unclear. In type 2 (non-insulin-dependent) diabetes mellitus, it is insulin-resistance in skeletal muscle, the chief site of insulin-mediated glucose disposal in humans, that predominantly accounts for the low rates of glucose clearance from the blood, and hence for impaired glucose tolerance. Human type 2 diabetes is characterized by a decrease in non-oxidative glucose storage (muscle glycogen synthesis), and by the deposition of amyloid in the islets of Langerhans. Amylin is a 37-amino-acid peptide which is a major component of islet amyloid and has structural similarity to human calcitonin gene-related peptide-2 (CGRP-2; ref. 8). CGRP is a neuropeptide which may be involved in motor activity in skeletal muscle. We now report that human pancreatic amylin and rat CGRP-1 are potent inhibitors of both basal and insulin-stimulated rates of glycogen synthesis in stripped rat soleus muscle in vitro. These results may provide a basis for a new understanding of the molecular mechanisms that cause insulin resistance in skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / pharmacology*
  • Animals
  • Calcitonin / pharmacology
  • Calcitonin Gene-Related Peptide
  • Dose-Response Relationship, Drug
  • Glycogen / metabolism
  • In Vitro Techniques
  • Insulin / pharmacology
  • Insulin Resistance*
  • Islet Amyloid Polypeptide
  • Lactates / biosynthesis
  • Male
  • Muscles / drug effects
  • Muscles / metabolism*
  • Neuropeptides / pharmacology*
  • Rats
  • Rats, Inbred Strains


  • Amyloid
  • Insulin
  • Islet Amyloid Polypeptide
  • Lactates
  • Neuropeptides
  • Glycogen
  • Calcitonin
  • Calcitonin Gene-Related Peptide