Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro.
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.
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide; D004305:Dose-Response Relationship, Drug; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D058228:Islet Amyloid Polypeptide; D007773:Lactates / Q000096:biosynthesis; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D007773:Lactates; D009479:Neuropeptides; D006003:Glycogen; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide