Glucose‐dependent insulinotropic polypeptide deficiency reduced fat accumulation and insulin resistance, but deteriorated bone loss in ovariectomized mice

Abstract

Given the established roles of glucose‐dependent insulinotropic polypeptide (GIP) in promoting fat storage and bone formation, we assessed the contribution of GIP to obesity and osteopenia in ovariectomized mice with a gene encoding green fluorescent protein (GFP) inserted into the GIP locus, in which GIP was either reduced (GIP gfp/+ ) or absent (GIP gfp/gfp ). In GIP gfp/gfp mice, weight gain, subcutaneous and visceral fat mass were reduced, and glucose intolerance was improved compared with wild‐type mice with the same magnitude of insulin responses. Cancellous bone mineral density and bone cortical thickness were reduced in GIP gfp/gfp mice compared with wild‐type mice. In GIP gfp/+ mice, weight gain, glucose intolerance and cancellous bone mineral density were not different from that of wild‐type mice. These results indicate that the total elimination of GIP ameliorates weight gain and adiposity in ovariectomized mice, but it enhances osteopenia, particularly in cancellous bone by partly suppressing bone formation.

GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease–A Systematic Review

“…However, overall effects of GIP at pharmacological concentrations are likely to be protective against atherosclerosis both in non-diabetic and diabetic conditions in vivo. Furthermore, recent in vivo studies have demonstrated multiple beneficial effects of GIP on diabetes-related diseases, such as Alzheimer's disease [129][130][131][132][133][134] and osteoporosis [135][136][137][138][139][140][141][142][143][144][145][146]. These findings suggest that dual or triple agonists including GIPR, which will be available in the near future [54][55][56], could be comprehensive treatment for diabetes and its related disorders.…”

Glucose‐dependent insulinotropic polypeptide receptor antagonist treatment causes a reduction in weight gain in ovariectomised high fat diet‐fed mice

“…Furthermore, postmenopausal women have increased plasma GIP levels (Ranganath et al, 1998), which are reduced by oestrogen replacement therapy (Sztefko et al, 2005). GIP receptor KO in ovariectomised mice causes, as for male mice, resistance to diet‐induced weight gain (Isken et al, 2008; Shimazu‐Kuwahara et al, 2019). Obesity treatment based on GIP receptor antagonism could therefore be of relevance to this part of the population.…”