Glucagon Receptor Knockout Prevents Insulin-Deficient Type 1 Diabetes in Mice

摘要: OBJECTIVE To determine the role of glucagon action in metabolic phenotype untreated insulin deficiency. RESEARCH DESIGN AND METHODS We compared pertinent clinical and parameters receptor-null (Gcgr −/− ) mice wild-type +/+ controls after equivalent destruction β-cells. used a double dose streptozotocin to maximize β-cell destruction. RESULTS Gcgr became hyperglycemic (>500 mg/dL), hyperketonemic, polyuric, cachectic had be killed 6 weeks. Despite comparable mice, none foregoing or laboratory manifestations diabetes appeared. There was marked α-cell hyperplasia hyperglucagonemia (∼1,200 pg/mL), but hepatic phosphorylated cAMP response element binding protein phosphoenolpyruvate carboxykinase mRNA were profoundly reduced with diabetes—evidence that been effectively blocked. Fasting glucose levels oral intraperitoneal tolerance tests normal. Both fasting nonfasting free fatty acid β-hydroxy butyrate lower. CONCLUSIONS conclude blocking prevents deadly derangements type 1 diabetic mice.