Abnormal calcium handling by perifused pancreatic islets from neonatal streptozotocin diabetic model rats.
To elucidate the mechanism of impaired insulin release in case of non-insulin-dependent diabetes (NIDDM), we investigated insulin release and 45Ca++ efflux from perifused islets obtained from neonatal streptozotocin diabetic model rats. The model rats were prepared by the intraperitoneal administration of 65 mg/kg streptozotocin (STZ) to neonatal males. Rats treated with STZ did not differ from controls in body weight from 1 week to 16 weeks. The model rats had significant hyperglycemia both in the fasting state and after intraperitoneal administration of 2 g/kg glucose. Although the diameter of the islets from the model rats was not significantly different from that of controls, immunoreactivity to anti-insulin was slightly diminished, and degranulation was slightly observed in B-cells. Insulin content was reduced to 45.6% of the control. Insulin release from the perifused islets of STZ-treated rats responded little to 16.7 mmol/L glucose, but normally to 20 mmol/L arginine in the presence of 5.5 mmol/L glucose. In experiments to test the 45Ca++ efflux from the perifused islets prelabeled with 45Ca++, a rise of 45Ca++ efflux concomitant with the second phase of insulin release from the islets of the model rats was inhibited although a sharp increase of 45Ca++ efflux concomitant with the first phase of insulin release was maintained. 45Ca++ uptake for 30 minutes was reduced in the islets from the model rats in the basal and stimulated state of insulin secretion although the incremental 45Ca++ uptake was similar. It is possible that the abnormal calcium handling in pancreatic B-cells may be one of the causes of defect in insulin release in our model rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Hashimoto
N
N
Kanatsuka
A
A
Makino
H
H
Sakurada
M
M
Iwaoka
H
H
Yoshida
S
S
Horie
H
H
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D001120:Arginine; D005947:Glucose; D002118:Calcium