Attenuation of FGF21 signalling might aggravate the impairment of glucose homeostasis during the high sucrose diet induced transition from prediabetes to diabetes in WNIN/GR-Ob rats

Abstract

Fibroblast growth factor 21 (FGF21) has emerged as a pleiotropic hormone and is known for its beneficiary roles in the management of diabetes and hyperglycaemia. However, the role of FGF21 during the transition from prediabetes to diabetes still remains unclear. Hence, the present study is aimed to understand the regulation of glucose homeostasis by FGF21 during the transition from prediabetes to diabetes in WNIN/GR-Ob rats.A total of 36 WNIN/GR-Ob obese male rats (28 days old) were divided into control and high sucrose (HS) groups and were fed ad libitum with their respective diets. These groups were sacrificed at different time points (week 1, 6, and 12) and various physical, biochemical, and molecular mediators were assessed to address FGF21 mediated glucose homeostasis.The study results revealed that rats developed impaired glucose tolerance and insulin resistance by exhibiting delayed glucose clearance from circulation, elevated fasting insulin, increased AUC glucose and HOMA-IR scores significantly; thereby rats demonstrated prediabetes by week 6 and diabetes complications by week 12. In line with the above, differential expression of genes attributed to FGF21 mediated glucose homeostasis, i.e., PPARα, FGF21, β-klotho, PPARγ, Adiponectin, Akt, and UCP1 suggest that the acute insulin sensitizing effect of FGF21 was significantly impaired during prediabetes to diabetes transition. In addition, increased gene and protein expression of FGF21 during the transition compared to controls could be a compensatory response to possibly counteract the metabolic stress imposed by high sucrose diet in WNIN/GR-Ob rats of the experimental group.Findings from the current study emphasize the potential role of FGF21 in glucose homeostasis and its attenuation might aggravate glucose impairment during the transition from prediabetes to diabetes in high sucrose diet induced WNIN/GR-Ob rats.