HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/E497    most recent 00048.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (28) Citing Articles via Google Scholar Google Scholar Articles by Stevens, M. J. Articles by Sima, A. A. F. Search for Related Content PubMed PubMed Citation Articles by Stevens, M. J. Articles by Sima, A. A. F.

C-peptide corrects endoneurial blood flow but not oxidative stress in type 1 BB/Wor rats

¹Section of Endocrinology, Department of Internal Medicine, University of Michigan, Ann Arbor 48109; ²Department of Pathology, ³Department of Neurology, and ⁴Morris Hood Jr. Comprehensive Diabetes Center, Wayne State University, Detroit, Michigan 48201

Submitted 2 February 2004 ; accepted in final form 24 April 2004

Oxidative stress and neurovascular dysfunction have emerged as contributing factors to the development of experimental diabetic neuropathy (EDN) in streptozotocin-diabetic rodents. Additionally, depletion of C-peptide has been implicated in the pathogenesis of EDN, but the mechanisms of these effects have not been fully characterized. The aims of this study were therefore to explore the effects of diabetes on neurovascular dysfunction and indexes of nerve oxidative stress in type 1 bio-breeding Worcester (BB/Wor) rats and type 2 BB Zucker-derived (ZDR)/Wor rats and to determine the effects of C-peptide replacement in the former. Motor and sensory nerve conduction velocities (NCVs), hindlimb thermal thresholds, endoneurial blood flow, and indicators of oxidative stress were evaluated in nondiabetic control rats, BB/Wor rats, BB/Wor rats with rat II C-peptide replacement (75 nmol C-peptide·kg body wt^–1·day^–1) for 2 mo, and diabetes duration-matched BBZDR/Wor rats. Endoneurial perfusion was decreased and oxidative stress increased in type 1 BB/Wor rats. C-peptide prevented NCV and neurovascular deficits and attenuated thermal hyperalgesia. Inhibition of nitric oxide (NO) synthase, but not cyclooxygenase, reversed the C-peptide-mediated effects on NCV and nerve blood flow. Indexes of oxidative stress were unaffected by C-peptide. In type 2 BBZDR/Wor rats, neurovascular deficits and increased oxidative stress were unaccompanied by sensory NCV slowing or hyperalgesia. Therefore, nerve oxidative stress is increased and endoneurial perfusion decreased in type 1 BB/Wor and type 2 BBZDR/Wor rats. NO and neurovascular mechanisms, but not oxidative stress, appear to contribute to the effects of C-peptide in type 1 EDN. Sensory nerve deficits are not an inevitable consequence of increased oxidative stress and decreased nerve perfusion in a type 2 diabetic rodent model.

type 1 and type 2 diabetic neuropathy; oxidative stress

This article has been cited by other articles:

				R. S. Guleria, J. Pan, D. DiPette, and U. S. Singh Hyperglycemia Inhibits Retinoic Acid-Induced Activation of Rac1, Prevents Differentiation of Cortical Neurons, and Causes Oxidative Stress in a Rat Model of Diabetic Pregnancy Diabetes, December 1, 2006; 55(12): 3326 - 3334. [Abstract] [Full Text] [PDF]

				H. Kamiya, W. Zhang, K. Ekberg, J. Wahren, and A. A.F. Sima C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes Diabetes, December 1, 2006; 55(12): 3581 - 3587. [Abstract] [Full Text] [PDF]

				I. G. Obrosova, V. R. Drel, P. Pacher, O. Ilnytska, Z. Q. Wang, M. J. Stevens, and M. A. Yorek Oxidative-Nitrosative Stress and Poly(ADP-Ribose) Polymerase (PARP) Activation in Experimental Diabetic Neuropathy: The Relation Is Revisited Diabetes, December 1, 2005; 54(12): 3435 - 3441. [Abstract] [Full Text] [PDF]