Fig. 4: Mitochondrial complex I inhibition in intestinal epithelium is necessary for metformin to improve glycaemic control in obese mice.
From: Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control
a, Oral glucose tolerance test of diet-induced obese mice fed a high-fat diet (HFD; 60% lard) for 8–10 weeks. Mice were fasted overnight, followed by oral administration of vehicle (water) or metformin (100 mg per kg body weight) and an oral bolus of glucose (2 g per kg body weight) 30 min later. b, iAUC of a; Vil-Crevehicle n = 8, Vil-Cre:NDI1vehicle n = 13, Vil-Cremetformin n = 7, Vil-Cre:NDI1metformin n = 14. c, Oral glucose tolerance test of diet-induced obese mice fed a HFD for 8–10 weeks. Vehicle (water) or metformin (200 mg per kg body weight) was orally delivered, followed by an oral bolus of glucose (2 g per kg body weight) 30 min later in overnight-fasted mice. d, iAUC of c; Vil-Crevehicle n = 12, Vil-Cre:NDI1vehicle n = 14, Vil-Cremetformin n = 14, Vil-Cre:NDI1metformin n = 11. e, Glucose tolerance test in which diet-induced obese mice were overnight fasted, orally delivered vehicle (water) or metformin (200 mg per kg body weight) and then 30 min later intraperitoneally injected with glucose (2 g per kg body weight). f, iAUC of e; Vil-Crevehicle n = 16, Vil-Cre:NDI1vehicle n = 17, Vil-Cremetformin n = 15, Vil-Cre:NDI1metformin n = 15. g, Postprandial insulin levels after a fasting–refeeding assay in diet-induced obese mice; Vil-Crevehicle n = 16, Vil-Cre:NDI1vehicle n = 17, Vil-Cremetformin n = 16, Vil-Cre:NDI1metformin n = 17. h, Postprandial glucose levels after a fasting–refeeding assay in diet-induced obese mice; Vil-Crevehicle n = 14, Vil-Cre:NDI1vehicle n = 15, Vil-Cremetformin n = 16, Vil-Cre:NDI1metformin n = 15. All mice were started on a HFD at 8 weeks of age, and experiments were performed after 8–10 weeks of HFD feeding. In g and h, mice were fasted overnight, followed by an oral dose of vehicle (water) or metformin (200 mg per kg body weight); 30 min later, mice were refed ad libitum for 30 min, followed by blood collection. Data are presented as the mean ± s.e.m. Statistical significance was determined by two-way ANOVA with Bonferroni’s correction for multiple comparisons. *P < 0.05, **P < 0.01, ***P < 0.001.
