Endogenous nitric oxide inhibits glucose-induced insulin secretion by suppression of phosphofructokinase activity in

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Y Tsuura1, H Ishida, T Shinomura

  • 1Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Kyoto, Japan.

Biochemical and Biophysical Research Communications
|November 14, 1998
PubMed

Insights

Endogenous nitric oxide (NO) inhibits glucose-stimulated insulin secretion by suppressing phosphofructokinase activity in pancreatic beta-cells. This finding clarifies NO's role in glucose metabolism and insulin release.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Physiology

Background:

  • The precise physiological role of nitric oxide (NO) in insulin secretion remains unclear.
  • Existing research suggests NO influences glucose metabolism within pancreatic beta-cells.

Purpose of the Study:

  • To elucidate the physiological function of endogenous NO in beta-cell glucose metabolism.
  • To identify the specific molecular targets of NO involved in regulating insulin secretion.

Main Methods:

  • Western blotting to detect brain-type NO synthase (bNOS) expression in pancreatic islets.
  • Measurement of NO generation under conditions of elevated intracellular calcium (high glucose, K+ depolarization).
  • Assessment of insulin secretion in response to glucose, glyceraldehyde, and KIC in the presence of NOS blockers (L-NIO, 7-NI).
  • In vitro enzyme assays examining the effects of a NO donor (SNP) on glycolytic enzymes.

Main Results:

  • bNOS expression was confirmed in pancreatic islets.
  • NO generation increased with high glucose and K+ depolarization, and was inhibited by NOS blockers and Ca2+-free conditions.
  • NOS blockers enhanced glucose-induced insulin secretion but not secretion stimulated by glyceraldehyde or KIC.
  • Sodium nitroprusside (SNP) differentially affected glycolytic enzyme activity, suppressing phosphofructokinase while activating glucokinase and glucose-6-phosphate isomerase, ultimately inhibiting overall enzyme function.

Conclusions:

  • Endogenous NO plays an inhibitory role in glucose-stimulated insulin secretion.
  • The mechanism involves the suppression of phosphofructokinase activity within the glycolytic pathway.
  • This study provides critical insights into the intricate regulation of insulin release by NO in pancreatic beta-cells.

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