Effects of antidiabetic drugs in high-fat diet and streptozotocin-nicotinamide-induced type 2 diabetic mice.
Based on previously established methods, we developed an easily available type 2 diabetic mouse model that exhibits obesity and insulin resistance. We investigated the effects of several antidiabetic drugs on this new model, which was induced by a high-fat diet in combination with streptozotocin and nicotinamide injection. Male ICR mice were fed a high-fat diet (45% of calories as fat) for 3weeks and then intraperitoneally administered with nicotinamide (1000mg/kg) and streptozotocin (150mg/kg). These diabetic mice exhibited hyperglycemia and glucose intolerance as a result of the loss of early-phase insulin secretion. The mice also developed significant insulin resistance, hyperlipidemia and obesity. A single dose of mitiglinide, glibenclamide, sitagliptin, insulin, metformin and voglibose significantly improved glucose tolerance during a liquid meal tolerance test. Repeated administration of sitagliptin and rosiglitazone also improved hyperglycemia and insulin resistance. These results demonstrate that a high-fat diet combined with nicotinamide and streptozotocin injection induces a diabetic mouse model that replicates the metabolic characteristics of human type 2 diabetes. This diabetic model, which exhibits impaired insulin secretion, glucose intolerance, insulin resistance, and obesity, may be suitable to evaluate antidiabetic agents for the treatment of type 2 diabetes.
Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Japan. atsuo.tahara@jp.astellas.com
Atsuo
A
Tahara
Akiko
A
Matsuyama-Yokono
Masayuki
M
Shibasaki
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D004041:Dietary Fats / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009536:Niacinamide / Q000009:adverse effects*; D015203:Reproducibility of Results
D004041:Dietary Fats; D007004:Hypoglycemic Agents; D009536:Niacinamide