Microvascular responsiveness to C-peptide in normal and streptozotocin (STZ)-induced diabetic rats

The objective of this was to assess in vivo arteriolar vasodilator properties of C-peptide in a rat striated muscle preparation of normal and diabetic rats using television microscopy.; In the first part of study, we assessed the ability of C-peptide to induce dilation of small arterioles in the normal rat cremaster muscle. Exposure to increasing concentrations of C-peptide (10−2–10 −8 M) produced a dose-dependent vasodilation of third-order arterioles. The maximal dilation to C-peptide was approximately 48 ± 3% of that observed to nitroprusside (10−5M). Pretreatment with a non-vasodilator dose of insulin for 20 minutes potentiated the arteriolar dilator response to C-peptide. The dilation to C-peptide was abolished by pretreatment with either L-NAME, a non-specific inhibitor of nitric oxide synthase, or pretreatment with ouabain, a Na+, K+-ATPase inhibitor. These results suggest that C-peptide produced a concentration-dependent arteriolar vasodilation in small resistance vessels, which can be enhanced in the presence of insulin. This arteriolar dilation to C-peptide appears to be mediated by vascular mechanisms that require activation of nitric oxide synthase or Na+, K+-ATPase.; In the second part of study, we compared the vascular responses to C-peptide in both normal and STZ-induced diabetic rats. C-peptide produced a significant arteriolar dilation in control rats, but not in streptozotocin (STZ)-induced diabetic rats. Pretreatment with a non-vasodilatiog dose of insulin restored the arteriolar vasodilation to C-peptide in the STZ-induced diabetic rats. We also examined the role of C-peptide in the vasodilator response to insulin and found that topical application of insulin caused a concentration-dependent vasodilation that was not enhanced by C-peptide pretreatment in the control rats. In STZ-induced diabetic rats, insulin failed to produce significant dilation. However, pretreatment of C-peptide restored the arteriolar vasodialtion to insulin in diabetic rats. These results indicate a permissive interaction between insulin and C-peptide that is required for either agent to produce a vasodilatory response in STZ-induced diabetic rats. Impairment of this vasodilation mechanism may be involved in the vascular dysfunction associated with insulin-dependent diabetes mellitus.