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Hypoglycaemic Effects of Antidiabetic Drugs in Streptozotocin‐Nicotinamide‐Induced Mildly Diabetic and Streptozotocin‐Induced Severely Diabetic Rats
Author(s) -
Tahara Atsuo,
MatsuyamaYokono Akiko,
Nakano Ryosuke,
Someya Yuka,
Shibasaki Masayuki
Publication year - 2008
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2008.00321.x
Subject(s) - streptozotocin , glibenclamide , medicine , endocrinology , diabetes mellitus , metformin , sitagliptin , nicotinamide , insulin , vildagliptin , chemistry , biochemistry , enzyme
In this study, streptozotocin‐induced severely diabetic rats and streptozotocin‐nicotinamide‐induced mildly diabetic rats were established to compare their characteristics and to investigate the hypoglycaemic effects of antidiabetic drugs. Results show that in streptozotocin‐induced severely diabetic rats, the pancreatic insulin content decreased to approximately 10% of that in normal rats. These severely diabetic rats also exhibited marked hyperglycaemia and impaired glucose tolerance due to insulin secretory deficiency. In contrast, the pancreatic insulin content was approximately 50% of normal levels in streptozotocin‐nicotinamide‐induced mildly diabetic rats. These mildly diabetic rats exhibited moderate hyperglycaemia and impaired glucose tolerance due to loss of early‐phase insulin secretion. Voglibose (α‐glucosidase inhibitor), metformin (biguanide), glibenclamide (sulfonylurea), sitagliptin (dipeptidyl peptidase‐4 inhibitor) and insulin significantly improved glucose tolerance in streptozotocin‐nicotinamide‐induced mildly diabetic rats. In contrast, in streptozotocin‐induced severely diabetic rats, voglibose, metformin and insulin significantly improved glucose tolerance, but no significant effect was observed for glibenclamide and sitagliptin due to a decreased insulinotropic effect. These results suggest that streptozotocin‐nicotinamide‐induced mildly diabetic rats, which exhibit a mild decline in glucose tolerance due to loss of early‐phase insulin secretion, are sensitive to the hypoglycaemic effects of insulinotropic agents and have many pathological features resembling type 2 diabetes, which may be useful in the pharmacological investigation of numerous antidiabetic drugs.