In clinical, the ’fatigue’ of the pancreatic beta cells is a famous phenomenon in type 2 diabetes. Nowadays, researchers describe the several mechanisms of beta cell dysfunction, such as glucolipotoxicity, endoplasmic reticulum stress and oxidative stress. In 2012, Talchai et al. revealed that the beta cells were dedifferentiated in diabetes, and previously we showed that food restriction had the most manifold good effects to restore beta cell gene expression, among the known diabetic treatments that we tested. In the current study, we aimed to unveil which nutrients should be cut down to protect beta cell differentiation, sugar or fat. First, we performed the pair-feeding with db/+ and db/db to reduce food intake of db/db mice. We utilized the high-fat/low carbohydrate diet (HF) or low-fat/high carbohydrate (HC) diet which were adjusted to the same total calorie intake. Pair fed-db/db mice had better body weight and glucose tolerance control than ad libitum db/db group, as previously we reported, and there was no significant difference between HF and HC diet. Albeit the same metabolic profile, HC diet group had more enlarged islets and more dedifferentiated beta cell features, which indicated the compensatory beta cell response in HC diet group. Moreover, HC diet group showed more severe fatty liver than HF diet group, along with the elevated synthesis and accumulation of triglycerides and cholesterol in liver. We are now investigating the relationship between sugar load, insulin resistance in liver and beta cell dedifferentiation.


E. Ishida: None. X. Lei: None. E. Yamada: None. S. Okada: None. M. Yamada: None.


Japan Society for the Promotion of Science (18K16222)

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