Affiliation: | (1) Research Centre of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan;(2) Department of Sports Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Japan;(3) Department of Internal Medicine, Anjyo Kosei Hospital, Anjyo, Japan;(4) Department of Endocrinology, Second University Hospital, China Medical University, Shen Yang, China;(5) Section of Clinical Physiology, Department of Surgical Sciences, Karolinska Hospital N1:05, Karolinska Institutet, 171 76 Stockholm, Sweden;(6) Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden |
Abstract: | Studies of C-peptide cellular effects show that not only the full-length native peptide but also specific C-terminal fragments are biologically active in in vitro systems. In the present study, the effect of five C-peptide fragments and the native peptide on whole-body glucose turnover was studied in streptozotocin diabetic rats using the insulin clamp technique. Insulin was infused intravenously at 18 pmol kg–1 min–1 for 90 min and blood glucose concentration was clamped at 8 and 4 mM in diabetic and non-diabetic animals. A steady state was reached during the last 30 min of the study period. Rat C-peptide II and fragments comprising residues 27–31 and 28–31 were effective in augmenting glucose turnover in diabetic rats (+100% to 150%), while no significant effects were seen for segments 1–26, 11–19 and 11–15. The metabolic clearance rate for glucose during infusion of C-peptide or fragments 27–31 and 28–31 in diabetic rats was similar to that seen in non-diabetic animals. We conclude that C-terminal tetra- and pentapeptides, but not fragments from the middle segment of C-peptide, are as effective as the full-length peptide in stimulating whole-body glucose turnover in diabetic rats.Received 18 December 2003; received after revision 19 January 2004; accepted 21 January 2004 |