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C-peptide prevents and improves chronic Type I diabetic polyneuropathy in the BB/Wor rat.
Diabetologia 2001; 44(7):889-97D

Abstract

AIMS/HYPOTHESIS

Insulin and C-peptide exert neuroprotective effects and are deficient in Type I (insulin-dependent) diabetes mellitus but not in Type II (non-insulin-dependent) diabetes mellitus. These studies were designed to test the preventive and interventional effects of C-peptide replacement on diabetic polyneuropathy in the Type I diabetic BB/Wor rat.

METHODS

Diabetic BB/Wor rats were replaced with rat C-peptide from onset of diabetes and between 5 and 8 months of diabetes. They were examined at 2 and 8 months and compared to non-C-peptide replaced BB/Wor rats, Type II diabetic (non-C-peptide deficient) BB/Z rats and non-diabetic control rats. Animals were monitored as to hyperglycaemia and nerve conduction velocity (NCV). Acute changes such as neural Na+/K+-ATPase and paranodal swelling were examined at 2 months, morphometric and teased fiber analyses were done at 8 months.

RESULTS

C-peptide replacement for 2 months in Type I diabetic rats prevented the acute NCV defect by 59% (p < 0.005), the neural Na+/K+-ATPase defect by 55% (p < 0.001) and acute paranodal swelling by 61% (p < 0.001). Eight months of C-peptide replacement prevented the chronic nerve conduction defect by 71% (p < 0.001) and totally prevented axoglial dysjunction (p < 0.001) and paranodal demyelination (p < 0.001). C-peptide treatment from 5 to 8 months showed a 13% (p < 0.05) improvement in NCV, a 33% (p < 0.05) improvement in axoglial dysjunction, normalization (p < 0.001) of paranodal demyelination, repair of axonal degeneration (p < 0.01), and a fourfold (p < 0.001) increase in nerve fibre regeneration.

CONCLUSION/INTERPRETATION

C-peptide replacement of Type I BB/Wor-rats partially prevents acute and chronic metabolic, functional and structural changes that separate Type I diabetic polyneuropathy from its Type II counterpart suggesting that C-peptide deficiency plays a pathogenetic role in Type I diabetic polyneuropathy.

Authors+Show Affiliations

Department of Pathology, Wayne State University, Detroit, Michigan 48201, USA. asima@med.wayne.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11508275

Citation

Sima, A A., et al. "C-peptide Prevents and Improves Chronic Type I Diabetic Polyneuropathy in the BB/Wor Rat." Diabetologia, vol. 44, no. 7, 2001, pp. 889-97.
Sima AA, Zhang W, Sugimoto K, et al. C-peptide prevents and improves chronic Type I diabetic polyneuropathy in the BB/Wor rat. Diabetologia. 2001;44(7):889-97.
Sima, A. A., Zhang, W., Sugimoto, K., Henry, D., Li, Z., Wahren, J., & Grunberger, G. (2001). C-peptide prevents and improves chronic Type I diabetic polyneuropathy in the BB/Wor rat. Diabetologia, 44(7), pp. 889-97.
Sima AA, et al. C-peptide Prevents and Improves Chronic Type I Diabetic Polyneuropathy in the BB/Wor Rat. Diabetologia. 2001;44(7):889-97. PubMed PMID: 11508275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - C-peptide prevents and improves chronic Type I diabetic polyneuropathy in the BB/Wor rat. AU - Sima,A A, AU - Zhang,W, AU - Sugimoto,K, AU - Henry,D, AU - Li,Z, AU - Wahren,J, AU - Grunberger,G, PY - 2001/8/18/pubmed PY - 2002/1/5/medline PY - 2001/8/18/entrez SP - 889 EP - 97 JF - Diabetologia JO - Diabetologia VL - 44 IS - 7 N2 - AIMS/HYPOTHESIS: Insulin and C-peptide exert neuroprotective effects and are deficient in Type I (insulin-dependent) diabetes mellitus but not in Type II (non-insulin-dependent) diabetes mellitus. These studies were designed to test the preventive and interventional effects of C-peptide replacement on diabetic polyneuropathy in the Type I diabetic BB/Wor rat. METHODS: Diabetic BB/Wor rats were replaced with rat C-peptide from onset of diabetes and between 5 and 8 months of diabetes. They were examined at 2 and 8 months and compared to non-C-peptide replaced BB/Wor rats, Type II diabetic (non-C-peptide deficient) BB/Z rats and non-diabetic control rats. Animals were monitored as to hyperglycaemia and nerve conduction velocity (NCV). Acute changes such as neural Na+/K+-ATPase and paranodal swelling were examined at 2 months, morphometric and teased fiber analyses were done at 8 months. RESULTS: C-peptide replacement for 2 months in Type I diabetic rats prevented the acute NCV defect by 59% (p < 0.005), the neural Na+/K+-ATPase defect by 55% (p < 0.001) and acute paranodal swelling by 61% (p < 0.001). Eight months of C-peptide replacement prevented the chronic nerve conduction defect by 71% (p < 0.001) and totally prevented axoglial dysjunction (p < 0.001) and paranodal demyelination (p < 0.001). C-peptide treatment from 5 to 8 months showed a 13% (p < 0.05) improvement in NCV, a 33% (p < 0.05) improvement in axoglial dysjunction, normalization (p < 0.001) of paranodal demyelination, repair of axonal degeneration (p < 0.01), and a fourfold (p < 0.001) increase in nerve fibre regeneration. CONCLUSION/INTERPRETATION: C-peptide replacement of Type I BB/Wor-rats partially prevents acute and chronic metabolic, functional and structural changes that separate Type I diabetic polyneuropathy from its Type II counterpart suggesting that C-peptide deficiency plays a pathogenetic role in Type I diabetic polyneuropathy. SN - 0012-186X UR - https://www.unboundmedicine.com/medline/citation/11508275/C_peptide_prevents_and_improves_chronic_Type_I_diabetic_polyneuropathy_in_the_BB/Wor_rat_ L2 - https://dx.doi.org/10.1007/s001250100570 DB - PRIME DP - Unbound Medicine ER -