We have previously demonstrated that Cpeptide stimulates glucose transport in skeletal muscle from non-diabetic subjects in a dose-dependent manner. To further elucidate the mechanism by which C-peptide activates glucose transport, we investigated the influence of human recombinant Cpeptide on receptor and post-receptor events involved in the glucose transport process. Human skeletal muscle specimens were obtained from the vastus lateralis by means of an open biopsy procedure. Stimulation of isolated muscle strips from healthy control subjects with supra-physiological concentrations of insulin (6,000 pmol/1) and C-peptide (2,500 pmol/1), did not further augment the twofold increase in the rate of 3-o-methylglucose transport induced by either stimulus alone. C-peptide did not displace 125I-insulin binding from partially purified receptors, nor did it activate receptor tyrosine kinase activity. Tyrosine-labelled 125I-C-peptide did not bind specifically to crude membranes prepared from skeletal muscle, or to any serum protein other than albumin. The [3-adr-energic receptor stimulation with isoproterenol inhibited insulin-but not C-peptide-mediated 3-o-methylglucose transport by 63+18% (p<0.01), whereas the cyclic AMP analogue, Bt2cAMR abolished the insulin-and C-peptide-stimulated 3-o-methylglucose transport. C-peptide (600 pmol/1) increased 3-o-methylglucose transport 1.8 + 0.2-fold in skeletal muscle specimens from patients with insulin-dependent diabetes mellitus. In conclusion, Cpeptide stimulates glucose transport by a mechanism independent of insulin receptor and tyrosine kinase activation. In contrast to the effect on insulin-stimulated glucose transport, catecholamines do not appear to have a counter regulatory action on C-peptide-mediated glucose transport. [Diabetologia (1996) 39: 306-313] Keywords Glucose transport, insulin receptor, insulin binding, insulin receptor tyrosine kinase, human skeletal muscle, C-peptide, insulin, catecholamines, insulin-dependent diabetes mellitus.
C-peptide is a 31-amino acid connecting peptide associated with the insulin molecule in the pancreatic beta cells and is necessary for the formation of the proinsulin molecule [1]. As proinsulin is cleaved by