C-PEPTIDE STIMULATES GLUCOSE-TRANSPORT IN ISOLATED HUMAN SKELETAL-MUSCLE INDEPENDENT OF INSULIN-RECEPTOR AND TYROSINE KINASE ACTIVATION

We have previously demonstrated that C-peptide stimulates glucose tran sport in skeletal muscle from non-diabetic subjects in a dose-dependen t manner. To further elucidate the mechanism by which C-peptide activa tes glucose transport, we investigated the influence of human recombin ant C-peptide on receptor and post-receptor events involved in the glu cose transport process. Human skeletal muscle specimens were obtained from the vastus lateralis by means of an open biopsy procedure. Stimul ation of isolated muscle strips from healthy control subjects with sup ra-physiological concentrations of insulin (6,000 pmol/l) and C-peptid e (2,500 pmol/l), 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 I-125-insulin binding from partially purifi ed receptors, nor did it activate receptor tyrosine kinase activity. T yrosine-labelled I-125-C-peptide did not bind specifically to crude me mbranes prepared from skeletal muscle, or to any serum protein other t han albumin. The beta-adrenergic receptor stimulation with isoproteren ol inhibited insulin- but not C-peptide-mediated 3-o-methylglucose tra nsport by 63 +/- 18% (p < 0.01), whereas the cyclic AMP analogue, Bt2c AMP, abolished the insulin- and C-peptide-stimulated 3-o-methylglucose transport. C-peptide (600 pmol/l) increased 3-o-methylglucose transpo rt 1.8 +/- 0.2-fold in skeletal muscle specimens from patients with in sulin-dependent diabetes mellitus. In conclusion, C-peptide stimulates glucose transport by a mechanism independent of insulin receptor and tyrosine kinase activation. In contrast to the effect on insulin-stimu lated glucose transport, catecholamines do not appear to have a counte r regulatory action on C-peptide-mediated glucose transport.