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A high-fat diet not only leads to obesity, but also leads to a predisposition towards insulin resistance (IR), which is characterized by hyperinsulinemia and reduced glucose tolerance. However, the etiology of IR remains to be fully elucidated. The present study investigated whether calcium-sensing receptor (CaSR) is involved in the development of IR in rats fed a high-fat diet. IR was induced in the rats by feeding with a fat emulsion via gavage for 2, 4, 6 or 8 weeks. Reverse transcription-quantitative polymerase chain reaction (RT-q-PCR) and western blot analysis were performed to investigate whether CaSR-associated proteins were affected. The gavage of fat emulsion for 8 weeks induced a notable decline in the insulin sensitivity index (ISI) between -4.98 and -5.60. With 6 weeks of gavage, a significant difference in the ISI was observed between the IR and control groups. The results of the RT-qPCR and western blot analysis demonstrated that phosphatidylinositol 3-kinase/Akt pathway, which is a pathway closely associated with the CaSR signaling pathway, was significantly inhibited in the rats with IR. The results of the present study provided evidence that CaSR is associated with the development of IR in rats fed a high-fat diet and suggested that CaSR may be important in the pathogenesis of diabetes.

Calcium-sensing receptor is involved in the pathogenesis of fat emulsion-induced insulin resistance in rats