Insulin therapy does not diminish beta-cell damage in the neonatal streptozotocin-injected rat.
In recent years it was suggested that in type 2 diabetes mellitus glucose exerts a direct toxic effect: the hyperglycaemic state itself could contribute to the defects in insulin secretion. We studied the effects of insulin treatment on pancreatic insulin content in neonatal Wistar rats made hyperglycaemic with streptozotocin (SZ, 90 mg/kg, injected intraperitoneally at two days of age). Our hypothesis was that normoglycaemia effected by insulin treatment could diminish the beta-cell damage in these animals. Insulin-treated animals received Lente MC insulin (8 mU/g body weight/day) during the first six days after SZ-injection. At four days of age, blood glucose levels (BG) in the fed state were 5.9 +/- 1.0 mmol/l in control animals (n = 14), whereas all untreated SZ-animals (n = 10) showed BG above 11 mmol/l (mean 15.9 +/- 3.4 mmol/l). In all 11 insulin-treated SZ-animals BG was below 10 mmol/l (mean 4.3 +/- 2.7 mmol/l). At 10 days of age plasma insulin levels did not differ between the three groups. However, pancreatic insulin content was 114 +/- 37 ng/mg tissue in the insulin-treated, and 93 +/- 34 ng/mg tissue (p = ns) in the untreated SZ-animals, compared to 516 +/- 257 ng/mg tissue in the controls (p less than 0.001). BG at four days and the pancreatic insulin contents at 10 days were not correlated. We conclude that intraperitoneal streptozotocin injection in neonatal rats produced marked hyperglycaemia and reduction of pancreatic insulin content. Insulin treatment did not result in improved recovery of the insulin stores in the pancreas. Thus, the additive toxic effect of hyperglycaemia on the beta-cells could not be demonstrated.
Wolffenbuttel
B H
BH
Department of Internal Medicine III, University Hospital, Maastricht, The Netherlands.
Vreeburg
J
J
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007328:Insulin / Q000032:analysis / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D002784:Cholesterol