M Sjöquist1, W Huang, B L Johansson. 1. Department of Physiology, Biomedicum, Uppsala University, Sweden. Mats.Sjoquist@Physiology.uu.se
Abstract
BACKGROUND: C-peptide has been reported to have biological effects on renal function early in the course of diabetes. This investigation was initiated to elucidate and amplify these findings with respect to protein leakage, hyperfiltration and renal functional reserve in diabetic rats. METHODS: Acute effects of 140 minutes i.v. infusion of human C-peptide (0.5 nmol x min(-1) x kg(-1) body wt) on renal function and urinary protein leakage were studied in anesthetized diabetic male rats two weeks after streptozotocin injection without insulin treatment. Streptozotocin-induced diabetic rats were studied with (N = 6) and without C-peptide (N = 11) treatment. The two groups showed a similarly elevated blood glucose concentration during the study. Age-matched normal rats served as controls (N = 5). Glomerular filtration rate (GFR) was measured by inulin clearance in the basal state and during a 60-minute glycine infusion (0.22 mmol x min(-1) x kg(-1) body wt)-resembling a protein load challenge-to test the renal functional reserve in all three groups. RESULTS: In the basal state, the non-C-peptide-treated diabetic rats displayed increased GFR and increased total protein leakage compared with normal rats. Whereas normal rats responded to glycine infusion with an increase in GFR, no increase occurred in diabetic rats not treated with C-peptide. In diabetic rats given C-peptide, this reduced the initial glomerular hyperfiltration prior to glycine infusion. This indicates a specific effect, since a control peptide with the same amino acid composition as C-peptide, but in a randomized sequence, had no such effect. C-peptide also restored half of the normal renal functional reserve and resulted in 70% lower (P < 0.05) total protein leakage compared with that in rats not given C-peptide. CONCLUSION: Thus, short-term infusion of C-peptide had beneficial effects on protein leakage and hyperfiltration and improved the renal functional reserve in rats with experimental diabetes.
BACKGROUND:C-peptide has been reported to have biological effects on renal function early in the course of diabetes. This investigation was initiated to elucidate and amplify these findings with respect to protein leakage, hyperfiltration and renal functional reserve in diabeticrats. METHODS: Acute effects of 140 minutes i.v. infusion of humanC-peptide (0.5 nmol x min(-1) x kg(-1) body wt) on renal function and urinary protein leakage were studied in anesthetized diabetic male rats two weeks after streptozotocin injection without insulin treatment. Streptozotocin-induced diabeticrats were studied with (N = 6) and without C-peptide (N = 11) treatment. The two groups showed a similarly elevated blood glucose concentration during the study. Age-matched normal rats served as controls (N = 5). Glomerular filtration rate (GFR) was measured by inulin clearance in the basal state and during a 60-minute glycine infusion (0.22 mmol x min(-1) x kg(-1) body wt)-resembling a protein load challenge-to test the renal functional reserve in all three groups. RESULTS: In the basal state, the non-C-peptide-treated diabeticrats displayed increased GFR and increased total protein leakage compared with normal rats. Whereas normal rats responded to glycine infusion with an increase in GFR, no increase occurred in diabeticrats not treated with C-peptide. In diabeticrats given C-peptide, this reduced the initial glomerular hyperfiltration prior to glycine infusion. This indicates a specific effect, since a control peptide with the same amino acid composition as C-peptide, but in a randomized sequence, had no such effect. C-peptide also restored half of the normal renal functional reserve and resulted in 70% lower (P < 0.05) total protein leakage compared with that in rats not given C-peptide. CONCLUSION: Thus, short-term infusion of C-peptide had beneficial effects on protein leakage and hyperfiltration and improved the renal functional reserve in rats with experimental diabetes.
Authors: Elizabeth R Flynn; Jonathan Lee; Zachary M Hutchens; Alejandro R Chade; Christine Maric-Bilkan Journal: J Diabetes Complications Date: 2013-08-29 Impact factor: 2.852
Authors: R Taylor Sawyer; Elizabeth R Flynn; Zachary M Hutchens; Jan M Williams; Michael R Garrett; Christine Maric-Bilkan Journal: Am J Physiol Renal Physiol Date: 2012-07-18
Authors: T Kitamura; K Kimura; B D Jung; K Makondo; S Okamoto; X Cañas; N Sakane; T Yoshida; M Saito Journal: Biochem J Date: 2001-04-01 Impact factor: 3.857
Authors: Maria J Chen; P Peter Chiou; Bih-Ying Yang; Hung Chieh Lo; Jin-Ki Son; Jerry Hendricks; George Bailey; Thomas T Chen Journal: In Vitro Cell Dev Biol Anim Date: 2004 Mar-Apr Impact factor: 2.416