Decreased K-ATP Channel Activity Contributes to the Low Glucose Threshold for Insulin Secretion of Rat Neonatal Islets

초록

Transitional hypoglycemia in normal newborns occurs in the first 3 days of life and has clinical features consistent with hyperinsulinism. We found a lower threshold for glucose-stimulated insulin secretion from freshly isolated embryonic day (E) 22 rat islets, which persisted into the first postnatal days. The threshold reached the adult level by postnatal day (P) 14. Culturing P14 islets also decreased the glucose threshold. Freshly isolated P1 rat islets had a lower threshold for insulin secretion in response to 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid, a nonmetabolizable leucine analog, and diminished insulin release in response to tolbutamide, an inhibitor of beta-cell K-ATP channels. These findings suggested that decreased K-ATP channel function could be responsible for the lower glucose threshold for insulin secretion. Single-cell transcriptomic analysis did not reveal a lower expression of K-ATP subunit genes in E22 compared with P14 beta cells. The investigation of electrophysiological characteristics of dispersed beta cells showed that early neonatal and cultured cells had fewer functional K-ATP channels per unit membrane area. Our findings suggest that decreased surface density of K-ATP channels may contribute to the observed differences in glucose threshold for insulin release.

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