Link between the prorenin/renin receptor and glucose homeostasis in mice fed a high‐fat/high‐carbohydrate diet

Abstract

ObjectiveElucidate the role of the (P)RR in glucose homeostasis in mice fed high‐fat/high‐carbohydrate diet (HF/HC).Material and methods12 week‐old C57BL/6 male mice were placed on a HF/HC or normal diet (ND) and were treated with either (P)RR blocker [(P)RR‐B] or saline for 10 weeks. Body weight was assessed weekly. At the end of treatment, mice were euthanized and fat tissues from subcutaneous (SCF), peri‐gonadal (PGF), peri‐renal (PRF) localisation were separated, weighed and flash frozen. Blood was collected and plasma was flash frozen for future measurement of glucose, insulin and triglycerides. Gene expression for glucose transporters GLUT1 and GLUT4 were assessed by real‐time PCR.Results(P)RR‐B administration lowered weight gain in the HF/HC fed mice, whereas food intake didn't differ between the groups. Increases produced by the HF/HC in circulating glucose, insulin and triglycerides were significantly decreased. Insulin sensitivity measured by glucose‐insulin ratio was also improved by the (P)RR‐B. Altered GLUT1 and GLUT4 mRNA expression in mice on a HF/HC was improved by the (P)RR‐B, in line with the circulating metabolites data.Conclusion(P)RR‐B administration seems to improve glucose homeostasis, insulin sensitivity and GLUTs gene expression profile in mice fed a HF/HC.Research supported by CIHR, HFSC, CDA and Merck Frosst Canada