Characterization of the zebrafish as a model of ATP-sensitive potassium channel hyperinsulinism.

INTRODUCTION

Congenital hyperinsulinism (HI) is the leading cause of persistent hypoglycemia in infants. Current models to study the most common and severe form of HI resulting from inactivating mutations in the ATP-sensitive potassium channel (K) are limited to primary islets from patients and the mouse model. Zebrafish exhibit potential as a novel KHI model since they express canonical insulin secretion pathway genes and those with identified causative HI mutations. Moreover, zebrafish larvae transparency provides a unique opportunity for in vivo visualization of pancreatic islets.

RESEARCH DESIGN AND METHODS

We evaluated zebrafish as a model for KHI using a genetically encoded Ca sensor (ins:gCaMP6s) expressed under control of the insulin promoter in beta cells of an zebrafish line.

RESULTS

We observed significantly higher islet cytosolic Ca in vivo in compared with zebrafish larvae. Additionally, larval zebrafish had significantly lower whole body glucose and higher whole body insulin levels compared with controls. However, adult zebrafish do not show differences in plasma glucose, plasma insulin, or glucose tolerance when compared with zebrafish.

CONCLUSIONS

Our results identify that zebrafish larvae, but not adult fish, are a demonstrable novel model for advancement of HI research.