Exploration of the reason for hyperphagia in mice after the treatment of dapagliflozin

概要

［課程－２］
審査の結果の要旨
氏名李 恩旭

Sglt2 inhibitors are widely used to treat type 2 diabetes. Although the sglt2 inhibitors
have a favorable effect on body weight, it was reported that they have a stimulatory
effect on food intake. To seek the mechanism underlying the hyperphagia caused by the
sglt2 inhibitors, I examined the effect of dapagliflozin, a sglt2 inhibitor, on food intake,
body weight and glucose levels in a variety of models in which appetite-related
surgeries were performed. I observed the increase of food intake by the dapagliflozin
treatment in mice that received either total-gastrectomy (TG), partial lipectomy (PLT)
or sub-pancreatectomy (SPT). Interestingly, in the insulin-deficient diabetic model
induced by streptozotocin (STZ), the increase of food consumption by the dapagliflozin
treatment was not observed, suggesting a possible involvement of insulin in the
hyperphagic action of dapagliflozin. Understanding the mechanisms underlying the
compensatory hyperphagia will be helpful to achieve ideal glycemic control and weight
loss by the sglt2 inhibitors.

This study can explore the physiological changes, especially the changes in appetite
which is directly related to body fat during the combination of the sglt2 inhibitor
treatment and the fat loss surgeries. Therefore, this study can examine the effect of the
sglt2 inhibitor on the appetite in the models with the appetite-related surgeries of fat
loss after the sglt2 inhibitor administration.

よって本論文は博士（ 医 学 ）の学位請求論文として合格と認められる。