作者: Brendan K. Podell , David F. Ackart , Michael A. Richardson , James E. DiLisio , Bruce Pulford
DOI: 10.1242/DMM.025593
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摘要: Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, additional animal models that more closely replicate the pathogenesis human type are needed. The goal this study was to develop model in guinea pigs, which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes crucial development diabetes. Guinea pigs developed impaired tolerance after 8 weeks feeding on high-fat, high-carbohydrate diet, as determined by oral challenge. Diet-induced accompanied hyperplasia, compensatory hyperinsulinemia, dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone ineffective at inducing diabetic hyperglycemia failed sustained or fasting returned euglycemia within 21 days treatment. However, when diet-fed were treated STZ, persisted beyond post-STZ subsequently STZ demonstrated an insulin-secretory capacity consistent insulin-independent This state confirmed response antihyperglycemic drugs, metformin glipizide, resolved extended survival compared uncontrolled In study, we have sequential loss, through diet extensive optimization pig, resembles will prove useful without comorbidities, where pig serves relevant species.