| Autor: |
Jolivalt, C. G., Rodriguez, M., Wahren, J., Calcutt, N. A. |
| Předmět: |
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| Zdroj: |
Diabetes, Obesity & Metabolism; Aug2015, Vol. 17 Issue 8, p781-788, 8p |
| Abstrakt: |
Aims To investigate the efficacy of a pegylated C-peptide ( Peg- C-peptide) against indices of peripheral neuropathy in a mouse model of type 1 diabetes and to compare efficacy of this C-peptide analogue against that of the native molecule. Methods C57Bl/6 mice were injected with two consecutive doses of streptozotocin ( STZ) to induce type 1 diabetes. Mice were treated twice daily with native C-peptide [0.4-1.3 mg/kg subcutaneously (s.c.)] or twice weekly with Peg- C-peptide (0.1-1.3 mg/kg s.c.) for 20 weeks. Motor and sensory nerve conduction velocities, thermal and tactile responses and rate dependent H-wave depression were assessed after 20 weeks of diabetes. Foot skin intraepidermal fibres and corneal nerves were counted, and sciatic nerve substance P and plasma C-peptide levels were also determined. Results After 5 months of STZ-induced diabetes, mice exhibited significant motor and sensory nerve conduction slowing, thermal hypoalgesia, tactile allodynia and attenuation of rate-dependent depression of the H reflex. These functional disorders were accompanied by nerve substance P depletion but not loss of small sensory fibres in the hind paw epidermis or the cornea. The efficacy of twice-daily treatment with native C-peptide in preventing these disorders was matched or exceeded by twice-weekly treatment with Peg- C-peptide. Both native and Peg- C-peptide also increased corneal nerve occupancy in the sub-basal nerve plexus of control rats. Conclusions These data identify actions of C-peptide against novel and clinically pertinent aspects of diabetic neuropathy in mice and also establish Peg- C-peptide as a long-acting therapeutic method of potential clinical value. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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