Аннотация:
Objective: A low-carbohydrate diet (LC) can be beneficial to obese subjects with type2
diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 inhibitor (SGLT2i) presents
prompt glucose-lowering effects in subjects with T2DM. We investigated how LC and
SGLT2i could similarly or differently influence on the metabolic changes, including glucose,
lipid, and ketone metabolism in lean insulinopenic Akita mice. We also examined the
impacts of the combination.
Methods: Male Akita mice were fed ad libitum normal-carbohydrate diet (NC) as a control
or low-carbohydrate diet (LC) as an intervention for 8 weeks with or without SGLT2i
treatment. Body weight and casual bold glucose levels were monitored during the study,
in addition to measuring TG, NEFA, and ketone levels. We quantified gene expressions
involved in gluconeogenesis, lipid metabolism and ketogenesis in the liver and the kidney.
We also investigated the immunostaining analysis of pancreatic islets to assess the effect
of islet protection.
Results: Both LC and SGLT2i treatment reduced chronic hyperglycemia. Moreover, the
combination therapy additionally ameliorated glycemic levels and preserved the islet
morphology in part. LC but not SGLT2i increased body weight accompanied by
epididymal fat accumulation. In contrast, SGLT2i, not LC potentiated four-fold ketone
production with higher ketogenic gene expression, in comparison with the non-treated
Akita mice. Besides, the combination did not enhance further ketone production
compared to the SGLT2i alone.
Conclusions: Our results indicated that both LC and SGLT2i reduced chronic
hyperglycemia, and the combination presented synergistic favorable effects concomitantly with amelioration of islet morphology, while the combination did not
enhance further ketosis in Akita mice.