Fig. 3: Mitochondrial complex I inhibition in intestinal epithelium is necessary for metformin to improve glycaemic control in lean mice.
From: Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control
a, Oral glucose tolerance test of standard diet fed mice. 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, Incremental area under the curve (iAUC; arbitrary units) of a; Vil-Crevehicle n = 14, Vil-Cre:NDI1vehicle n = 10, Vil-Cremetformin n = 14, Vil-Cre:NDI1metformin n = 9. c, Oral glucose tolerance test of standard diet-fed mice. 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 = 11, Vil-Cre:NDI1vehicle n = 11, Vil-Cremetformin n = 11, Vil-Cre:NDI1metformin n = 13. e, Glucose tolerance test in which standard diet-fed mice were overnight fasted, then 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 = 10, Vil-Cre:NDI1vehicle n = 9, Vil-Cremetformin n = 11, Vil-Cre:NDI1metformin n = 9. g, Postprandial insulin levels after a fasting–refeeding assay in standard diet-fed mice; Vil-Crevehicle n = 14, Vil-Cre:NDI1vehicle n = 15, Vil-Cremetformin n = 13, Vil-Cre:NDI1metformin n = 13. h, Postprandial glucose levels after a fasting–refeeding assay in standard diet-fed mice; Vil-Crevehicle n = 7, Vil-Cre:NDI1vehicle n = 11, Vil-Cremetformin n = 7, Vil-Cre:NDI1metformin n = 10. SD, standard diet; IPGTT, intraperitoneal glucose tolerance test. All mice were male and 7–10 weeks of age. 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.
