Functional adenosine triphosphate-sensitive potassium channel is required in high-carbohydrate diet-induced increase in β-cell mass

J Diabetes Investig. 2019 Mar;10(2):238-250. doi: 10.1111/jdi.12907. Epub 2018 Sep 4.


Aims/introduction: A high-carbohydrate diet is known to increase insulin secretion and induce obesity. However, whether or not a high-carbohydrate diet affects β-cell mass (BCM) has been little investigated.

Materials and methods: Both wild-type (WT) mice and adenosine triphosphate-sensitive potassium channel-deficient (Kir6.2KO) mice were fed normal chow or high-starch (ST) diets for 22 weeks. BCM and the numbers of islets were analyzed by immunohistochemistry, and gene expression levels in islets were investigated by quantitative real-time reverse transcription polymerase chain reaction. MIN6-K8 β-cells were stimulated in solution containing various concentrations of glucose combined with nifedipine and glimepiride, and gene expression was analyzed.

Results: Both WT and Kir6.2KO mice fed ST showed hyperinsulinemia and body weight gain. BCM, the number of islets and the expression levels of cyclinD2 messenger ribonucleic acid were increased in WT mice fed ST compared with those in WT mice fed normal chow. In contrast, no significant difference in BCM, the number of islets or the expression levels of cyclinD2 messenger ribonucleic acid were observed between Kir6.2KO mice fed normal chow and those fed ST. Incubation of MIN6-K8 β-cells in high-glucose media or with glimepiride increased cyclinD2 expression, whereas nifedipine attenuated a high-glucose-induced increase in cyclinD2 expression.

Conclusions: These results show that a high-starch diet increases BCM in an adenosine triphosphate-sensitive potassium channel-dependent manner, which is mediated through upregulation of cyclinD2 expression.

Keywords: Adenosine triphosphate-sensitive potassium channel; Carbohydrate; β-Cell mass.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Blood Glucose / analysis
  • Cyclin D2 / metabolism*
  • Dietary Carbohydrates / adverse effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Potassium Channels, Inwardly Rectifying / physiology*
  • Weight Gain*


  • Blood Glucose
  • Ccnd2 protein, mouse
  • Cyclin D2
  • Dietary Carbohydrates
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • Adenosine Triphosphate