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AMP-activated protein kinase agonist dose dependently improves function and reduces apoptosis in glucotoxic

Hanna K Nyblom1, Ernest Sargsyan, Peter Bergsten

  • 1Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden. hanna.nyblom@mcb.uu.se

Journal of Molecular Endocrinology
|June 27, 2008
PubMed

Insights

AMP-activated protein kinase (AMPK) agonist AICAR improves beta-cell function under high glucose conditions. AICAR dose-dependently reduces apoptosis and restores glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Metabolic Research

Background:

  • Prolonged hyperglycemia impairs pancreatic beta-cell function, leading to reduced glucose-stimulated insulin secretion (GSIS) and increased apoptosis.
  • Glucose-induced lipid accumulation in beta-cells is implicated in these detrimental effects.

Purpose of the Study:

  • To investigate the effects of the AMP-activated protein kinase (AMPK) agonist, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), on impaired GSIS and apoptosis in beta-cells cultured under prolonged high glucose conditions.
  • To determine the dose-dependent effects of AICAR on beta-cell function and viability.

Main Methods:

  • Insulinoma (INS)-1E cells were cultured with 27 mM glucose, with or without 0.3 or 1 mM AICAR.
  • GSIS, insulin content, triglyceride (TG) levels, AMPK phosphorylation, and apoptosis markers (CHOP) were assessed.

Main Results:

  • AICAR at 0.3 mM reverted glucose-induced impairment of insulin release, while 1 mM AICAR did not significantly affect insulin content.
  • AICAR did not alter glucose-induced triglyceride accumulation.
  • 1 mM AICAR induced AMPK phosphorylation, reduced apoptotic cells, and lowered CHOP expression, indicating reduced apoptosis.

Conclusions:

  • AICAR demonstrates dose-dependent beneficial effects on beta-cell function and survival under prolonged hyperglycemic stress.
  • AICAR improves GSIS and reduces apoptosis without affecting cellular lipid accumulation.

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