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Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in human islets in type 2 diabetes and regulates

G da Silva Xavier1, H Farhan, H Kim

  • 1Section of Cell Biology, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK. g.dasilva-xavier@imperial.ac.uk

Diabetologia
|December 25, 2010
PubMed
Abstract

Insights

Per-arnt-sim (PAS) domain-containing protein kinase (PASK) regulates glucagon secretion. Lower PASK levels in type 2 diabetes suggest PASK as a potential therapeutic target.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Metabolic Diseases

Background:

  • Glucagon is a key hormone regulating blood glucose levels.
  • Dysregulation of glucagon secretion is implicated in type 2 diabetes.
  • The role of per-arnt-sim (PAS) domain-containing protein kinase (PASK) in glucagon regulation is not well understood.

Purpose of the Study:

  • To investigate the involvement of PASK in the regulation of glucagon secretion.
  • To explore the potential of PASK as a therapeutic target for type 2 diabetes.

Main Methods:

  • Quantitative PCR to measure PASK mRNA levels in human islets and mouse pancreatic cells.
  • Analysis of glucose tolerance, plasma hormone levels, and islet hormone secretion in Pask knockout mice.
  • In vitro studies using alpha-TC1-9 cells and human islets with PASK knockdown or overexpression.

Main Results:

  • PASK expression was reduced in islets from human type 2 diabetic patients.
  • Pask knockout mice exhibited elevated fasting blood glucose and plasma glucagon levels.
  • PASK depletion impaired glucose-inhibited glucagon secretion and affected insulin secretion.
  • PASK overexpression inhibited glucagon secretion, suggesting a role in its regulation.

Conclusions:

  • PASK plays a significant role in glucose-mediated regulation of glucagon secretion.
  • PASK may serve as a potential therapeutic target for managing type 2 diabetes.

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