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High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
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High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and beta-cell

Zhaoyun Zhang1, Chong Wee Liew, Diane E Handy

  • 1Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|December 25, 2009
PubMed

Insights

Glucose-6-phosphate dehydrogenase (G6PD) is crucial for pancreatic beta-cell survival in type 2 diabetes. Impaired G6PD activity under high glucose conditions leads to beta-cell loss, contributing to diabetes progression.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Metabolic Diseases

Background:

  • Type 2 diabetes is characterized by progressive loss of pancreatic beta cells.
  • Glucose-6-phosphate dehydrogenase (G6PD) generates NADPH, essential for antioxidant defense.
  • Beta cells are vulnerable to oxidative stress, implicated in diabetes pathogenesis.

Purpose of the Study:

  • To investigate the role of G6PD and NADPH in pancreatic beta-cell survival.
  • To determine if G6PD dysfunction contributes to beta-cell loss in diabetes.

Main Methods:

  • Utilized human and mouse islets, MIN6 cell line, and G6PD-deficient mice.
  • Assessed G6PD expression and activity under high glucose conditions.
  • Employed siRNA to inhibit G6PD and gene overexpression to study its effects.

Main Results:

  • High glucose reduced G6PD expression and activity in beta cells.
  • G6PD inhibition increased reactive oxygen species (ROS) and apoptosis, while decreasing proliferation and insulin secretion.
  • Overexpressing G6PD improved insulin secretion impaired by high glucose.
  • G6PD-deficient mice exhibited smaller islets and impaired glucose tolerance.

Conclusions:

  • G6PD is vital for pancreatic beta-cell function and survival.
  • Reduced G6PD activity under hyperglycemia is a potential mechanism for beta-cell loss in type 2 diabetes.
  • Targeting G6PD may offer therapeutic strategies for diabetes.

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