1. |
- Cotter, MA, et al.
(författare)
-
Effects of proinsulin C-peptide in experimental diabetic neuropathy: vascular actions and modulation by nitric oxide synthase inhibition
- 2003
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:7, s. 1812-1817
-
Tidskriftsartikel (refereegranskat)abstract
- Proinsulin C-peptide treatment can partially prevent nerve dysfunction in type 1 diabetic rats and patients. This could be due to a direct action on nerve fibers or via vascular mechanisms as C-peptide stimulates the nitric oxide (NO) system and NO-mediated vasodilation could potentially account for any beneficial C-peptide effects. To assess this further, we examined neurovascular function in streptozotocin-induced diabetic rats. After 6 weeks of diabetes, rats were treated for 2 weeks with C-peptide to restore circulating levels to those of nondiabetic controls. Additional diabetic groups were given C-peptide with NO synthase inhibitor NG-nitro-l-arginine (l-NNA) co-treatment or scrambled C-peptide. Diabetes caused 20 and 16% reductions in sciatic motor and saphenous sensory nerve conduction velocity, which were 62 and 78% corrected, respectively, by C-peptide. l-NNA abolished C-peptide effects on nerve conduction. Sciatic blood flow and vascular conductance were 52 and 41%, respectively, reduced by diabetes (P < 0.001). C-peptide partially (57–66%) corrected these defects, an effect markedly attenuated by l-NNA co-treatment. Scrambled C-peptide was without effect on nerve conduction or perfusion. Thus, C-peptide replacement improves nerve function in experimental diabetes, and the data are compatible with the notion that this is mediated by a NO-sensitive vascular mechanism.
|
|
2. |
- Ekberg, K, et al.
(författare)
-
Amelioration of sensory nerve dysfunction by C-Peptide in patients with type 1 diabetes
- 2003
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:2, s. 536-541
-
Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated that proinsulin C-peptide stimulates the activities of Na+,K+-ATPase and endothelial nitric oxide synthase, both of which are enzyme systems of importance for nerve function and known to be deficient in type 1 diabetes. The aim of this randomized double-blind placebo-controlled study was to investigate whether C-peptide replacement improves nerve function in patients with type 1 diabetes. Forty-nine patients without symptoms of peripheral neuropathy were randomized to either 3 months of treatment with C-peptide (600 nmol/24 h, four doses s.c.) or placebo. Forty-six patients (15 women and 31 men, aged 29 years, diabetes duration 10 years, and HbA1c 7.0%) completed the study. Neurological and neurophysiological measurements were performed before and after 6 and 12 weeks of treatment. At baseline the patients showed reduced nerve conduction velocities in the sural nerve (sensory nerve conduction velocity [SCV]: 50.9 ± 0.70 vs. 54.2 ± 1.2 m/s, P < 0.05) and peroneal nerve (motor nerve conduction velocity: 45.7 ± 0.55 vs. 53.5 ± 1.1 m/s, P < 0.001) compared with age-, height-, and sex-matched control subjects. In the C-peptide treated group there was a significant improvement in SCV amounting to 2.7 ± 0.85 m/s (P < 0.05 compared with placebo) after 3 months of treatment, representing 80% correction of the initial reduction in SCV. The change in SCV was accompanied by an improvement in vibration perception in the patients receiving C-peptide (P < 0.05 compared with placebo), whereas no significant change was detectable in cold or heat perception. In conclusion, C-peptide administered for 3 months as replacement therapy to patients with early signs of diabetic neuropathy ameliorates nerve dysfunction.
|
|
3. |
|
|
4. |
|
|
5. |
|
|
6. |
|
|