Characterization of streptozotocin-induced diabetic rats and pharmacodynamics of insulin formulations.
Morphological and functional changes of rat pancreatic islets caused by administration of streptozotocin (STZ) and the bioavailability of insulin formulations administered to STZ-induced diabetic rats with fasting (12 h) or non-fasting were investigated. Islets isolated from normal rats maintained a good three-dimensional structure and the islet yield was 962.5+/-86.5 islet equivalent number (IEQ, islets converted to an average diameter of 150 microm). In the diabetic group (>500 mg/ml blood glucose), the islet yield was only 44.4+/-8.3 IEQ and the islet was severely damaged. The minimum reduction of blood glucose of each formulation, such as insulin solution, microcrystal, and insulin microcrystal capsule, was shown to be 11.3, 11.0, and 16.3 mg/dl, respectively, at 6 h in fasting with diabetic rats. These results indicated that the administration of insulin formulations to the fasting groups increased the severe hypoglycemic effect of insulin action more than in non-fasting diabetic rats. The diabetic rat with fasting has a regulatory disorder in maintaining the blood glucose level. Accordingly, the validity of pharmacological availability as an optimal modeling of insulin formulations is best in non-fasting STZ-induced diabetic rats.
Lee
Jae-Jeong
JJ
Graduate School of Life Sciences and Biotechnology, Korea University, Seoul.
Yi
Ho-Young
HY
Yang
Jae-Won
JW
Shin
Jun-Seop
JS
Kwon
Jai-Hyun
JH
Kim
Chan-Wha
CW
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D007328:Insulin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin