Rat C peptide I and II stimulate glucose utilization in STZ-induced diabetic rats.
OBJECTIVE
To study the effects of physiological concentrations of rat proinsulin C peptide I and II, respectively, on whole body glucose utilization in streptozotocin diabetic and healthy rats.


METHODS
A sequential insulin clamp procedure was used (insulin infusion rates 3.0 and 30.0 mU.kg-1.min-1) in awake animals. C-peptide infusion rates were 0.05 and 0.5 nmol.kg-1.min-1. Blood glucose was clamped at 7.7 +/- 0.3 mmol/l in the diabetic rats and at 3.9 +/- 0.1 mmol/l in the healthy rats.


RESULTS
In diabetic rats infused at lower rates of C peptide and insulin, glucose utilization increased by 79-90% (p < 0.001) compared with diabetic animals infused with saline and insulin. Increasing the rate of C-peptide infusion tenfold did not elicit a statistically significant further increase in glucose utilization. C peptide I and II exerted similar effects. The metabolic clearance rate for glucose in the diabetic animals infused with C peptide was not different from that of the healthy rats. During high-dose insulin infusion (30.0 mU.kg-1.min-1) glucose utilization increased considerably and no statistically significant C-peptide effects were observed. About 85% of the increase in glucose utilization induced by C peptide could be blocked by treatment with N-monomethyl-L-arginine.


CONCLUSIONS
Physiological concentrations of homologous C peptide stimulate whole body glucose utilization in diabetic but not in healthy rats. C peptide I and II elicit similar effects. The influence of C peptide on glucose utilization may be mediated by nitric oxide.
Li
L
L
First Division of Health Promotion Science, Graduate School of Medicine, Nagoya University, Japan.
Oshida
Y
Y
Kusunoki
M
M
Yamanouchi
K
K
Johansson
B L
BL
Wahren
J
J
Sato
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000008:administration & dosage / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D061389:Insulin, Regular, Pork; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D061389:Insulin, Regular, Pork; C000006:insulin, neutral; D005947:Glucose