C-peptide potentiates the vasoconstrictor effect of neuropeptide Y in insulin-dependent diabetic patients

Recent findings suggest that proinsulin C-peptide improves renal and nerve function as well as microcirculation in patients with insulin-dependent dia betes possibly by stimulating Na-K+-ATPase activity. Furthermore, in vitro studies on proximal rat renal tubule cells show that the effect of C-peptid e on Na+, K+-ATPase activity is potentiated in the presence of the vasocons trictor peptide neuropeptide Y. The aim of the present study was to examine whether the effects of neuropeptide Y on resting forearm blood flow in ins ulin-dependent patients is altered in the presence of C-peptide. Forearm bl ood flow was measured by a plethysmographic method in eight insulin-depende nt patients and six healthy control subjects. Neuropeptide Y (20, 200 and 2 000 pmol min(-1)) was infused into the brachial artery before and during an i.v. infusion of C-peptide (5 pmol kg(-1) min(-1)). Basal blood flow was 3 6.7 +/- 2.2 mL min(-1) L-1 tissue. It decreased in a dose dependent manner by 11 +/- 2, 18 +/- 3 and 25 +/- 3%, respectively, during infusion of neuro peptide Y. Administration of C-peptide increased basal blood flow by 25 +/- 6%, to 46.3 +/- 3.5 mL min(-1) L-1 tissue (P < 0.01) and forearm glucose u ptake by 76 +/- 34% (P < 0.05). Infusion of the three doses of neuropeptide Y during administration of C-peptide decreased forearm blood flow by 14 +/ - 4, 22 +/- 3 and 42 +/- 4%. There was a significant difference (43%, P < 0 .001) between the reduction in blood flow evoked by the high dose (2000 pmo l min(-1)) of neuropeptide Y before and during C-peptide infusion. Similar differences were also obtained when data were calculated as changes in vasc ular resistance. C-peptide did not affect resting forearm blood flow or the response to neuropeptide Y in healthy controls. In conclusion, the present data demonstrate that C-peptide increases resting forearm blood flow and a ugments the vasoconstrictor effects of neuropeptide Y in insulin-dependent patients.