The flavonoid resokaempferol improves insulin secretion from healthy and dysfunctional pancreatic β-cells

The pharmacology of flavonoids on β-cell function is largely undefined especially in the context of defective secretion of insulin. We sought to identify flavonoids that increased the insulin-secreting function of β-cells and to explore the underlying mechanisms.

INS-1 β-cells in culture and islets of Langerhans isolated from control and diabetic male rats were used for insulin secretion experiments. Pharmacological and electrophysiological approaches were used for mechanistic studies.

Among a set of flavonoids, exposure of INS-1 β-cells to resokaempferol (ResoK) enhanced glucose-stimulated insulin secretion and therefore we further characterised its activity and its pharmacological mechanism. ResoK glucose-dependently enhanced insulin secretion in INS-1 β-cells and pancreatic islets isolated from rats. Mechanistically, whole cell patch clamp recordings in INS-1 cells showed that ResoK rapidly and dose-dependently enhanced the L-type Ca²⁺ current whereas it was inactive towards T-type Ca²⁺ current. Accordingly, pharmacological inhibition of L-type Ca²⁺ current but not T-type Ca²⁺ current blocked the effects of ResoK on glucose-stimulated insulin secretion. ResoK was still active on dysfunctional β-cells as it ameliorated glucose-stimulated insulin secretion in glucotoxicity-induced dysfunctional INS-1 cells and in pancreatic islets isolated from diabetic rats.

ResoK is a glucose-dependent activator of insulin secretion. Our results indicated that the effects of ResoK on insulin secretion involved its capacity to stimulate L-type Ca²⁺ currents in cultured β-cells. As ResoK was also effective on dysfunctional β-cells, our work provides a new approach to stimulating insulin secretion, using compounds based on the structure of ResoK.