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Metabolic coupling factors in pancreatic beta-cell signal transduction.

Publication ,  Journal Article
Newgard, CB; McGarry, JD
Published in: Annu Rev Biochem
1995

This chapter focuses on the biochemical mechanisms that mediate glucose-stimulated insulin secretion (GSIS) from beta-cells of the islets of Langerhans and the potentiating role played by fatty acids. We summarize evidence supporting the idea that glucose metabolism is required for GSIS and that the GLUT-2 facilitated glucose transporter and the glucose phosphorylating enzyme glucokinase play important roles in measuring changes in extracellular glucose concentration. The idea that glucose metabolism is linked to insulin secretion through a sequence of events involving changes in ATP:ADP ratio, inhibition of ATP-sensitive K+ channels, and activation of voltage-gated Ca2+ channels is critically reviewed, and the relative importance of ATP generated from glycolytic versus mitochondrial metabolism is evaluated. We also present the growing concept that an important signal for insulin secretion may reside at the linkage between glucose and lipid metabolism, specifically the generation of the regulatory molecule malonyl CoA that promotes fatty acid esterification and inhibits oxidation. Finally, we show that in contrast to its short term potentiating effect on GSIS, long-term exposure of islets to high levels of fatty acids results in beta-cell dysfunction, suggesting that hyperlipidemia associated with obesity may play a causal role in the diminished GSIS characteristic of non insulin-dependent diabetes mellitus (NIDDM).

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Published In

Annu Rev Biochem

DOI

ISSN

0066-4154

Publication Date

1995

Volume

64

Start / End Page

689 / 719

Location

United States

Related Subject Headings

  • Signal Transduction
  • Potassium Channels
  • Phosphorylation
  • Models, Biological
  • Mitochondria
  • Lipid Metabolism
  • Islets of Langerhans
  • Insulin Secretion
  • Insulin
  • Humans
 

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Newgard, C. B., & McGarry, J. D. (1995). Metabolic coupling factors in pancreatic beta-cell signal transduction. Annu Rev Biochem, 64, 689–719. https://doi.org/10.1146/annurev.bi.64.070195.003353
Newgard, C. B., and J. D. McGarry. “Metabolic coupling factors in pancreatic beta-cell signal transduction.Annu Rev Biochem 64 (1995): 689–719. https://doi.org/10.1146/annurev.bi.64.070195.003353.
Newgard CB, McGarry JD. Metabolic coupling factors in pancreatic beta-cell signal transduction. Annu Rev Biochem. 1995;64:689–719.
Newgard, C. B., and J. D. McGarry. “Metabolic coupling factors in pancreatic beta-cell signal transduction.Annu Rev Biochem, vol. 64, 1995, pp. 689–719. Pubmed, doi:10.1146/annurev.bi.64.070195.003353.
Newgard CB, McGarry JD. Metabolic coupling factors in pancreatic beta-cell signal transduction. Annu Rev Biochem. 1995;64:689–719.

Published In

Annu Rev Biochem

DOI

ISSN

0066-4154

Publication Date

1995

Volume

64

Start / End Page

689 / 719

Location

United States

Related Subject Headings

  • Signal Transduction
  • Potassium Channels
  • Phosphorylation
  • Models, Biological
  • Mitochondria
  • Lipid Metabolism
  • Islets of Langerhans
  • Insulin Secretion
  • Insulin
  • Humans