Glucokinase intrinsically regulates glucose sensing and glucagon secretion in pancreatic alpha cells.

Scientific Reports
Tilo MoedePer-Olof Berggren

Abstract

The secretion of glucagon by pancreatic alpha cells is regulated by a number of external and intrinsic factors. While the electrophysiological processes linking a lowering of glucose concentrations to an increased glucagon release are well characterized, the evidence for the identity and function of the glucose sensor is still incomplete. In the present study we aimed to address two unsolved problems: (1) do individual alpha cells have the intrinsic capability to regulate glucagon secretion by glucose, and (2) is glucokinase the alpha cell glucose sensor in this scenario. Single cell RT-PCR was used to confirm that glucokinase is the main glucose-phosphorylating enzyme expressed in rat pancreatic alpha cells. Modulation of glucokinase activity by pharmacological activators and inhibitors led to a lowering or an increase of the glucose threshold of glucagon release from single alpha cells, measured by TIRF microscopy, respectively. Knockdown of glucokinase expression resulted in a loss of glucose control of glucagon secretion. Taken together this study provides evidence for a crucial role of glucokinase in intrinsic glucose regulation of glucagon release in rat alpha cells.

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Citations

Mar 6, 2021·Molecular and Cellular Biochemistry·Carla P Barragán-ÁlvarezNestor E Díaz-Martínez
Jun 10, 2021·Diabetes, Obesity & Metabolism·Akinobu NakamuraYasuo Terauchi

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Methods Mentioned

BETA
PCR
ELISA
biosensor
Fluorescence
fluorescence-activated cell sorting
FACS
transfection
Assay

Software Mentioned

Excel
FIJI
GraphPad Prism
Origin
FlowJo
BD Attovision

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