Activation of autophagy through modulation of 5′-AMP-activated protein kinase protects pancreatic β-cells from high glucose

Diana Han, Byungho Yang, L. Karl Olson, Alexander Greenstein, Seung Hoon Baek, Kate J. Claycombe, John L. Goudreau, Seong Woon Yu, Eun Kyoung Kim

Research output: Contribution to journalArticle

Abstract

Chronic hyperglycaemia is detrimental to pancreatic β-cells by causing impaired insulin secretion and diminished β-cell function through glucotoxicity. Understanding themechanisms underlying β-cell survival is crucial for the prevention of β-cell failure associated with glucotoxicity. Autophagy is a dynamic lysosomal degradation process that protects organisms against metabolic stress. To date, little is known about the physiological function of autophagy in the pathogenesis of diabetes. In the present study, we explored the roles of autophagy in the survival of pancreatic β-cells exposed to high glucose using pharmacological and genetic manipulation of autophagy.We demonstrated that chronic high glucose increases autophagy in rat INS-1 (832/13) cells and pancreatic islets, and that this increase is enhanced by inhibition of 5′-AMP-activated protein kinase. Our results also indicate that stimulation of autophagy rescues pancreatic β-cells from highglucose-induced cell death and inhibition of autophagy augments caspase-3 activation, suggesting that autophagy plays a protective role in the survival of pancreatic β-cells. Greater knowledge of the molecular mechanisms linking autophagy and β-cell survival may unveil novel therapeutic targets needed to preserve β-cell function.

Original languageEnglish (US)
Pages (from-to)541-551
Number of pages11
JournalBiochemical Journal
Volume425
Issue number3
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

Fingerprint

AMP-Activated Protein Kinases
Autophagy
Chemical activation
Modulation
Glucose
Cells
Cell Survival
Cell death
Medical problems
Caspase 3
Rats
Insulin
Degradation
Physiological Stress
Islets of Langerhans
Hyperglycemia
Cell Death
Pharmacology

Keywords

  • 5′-AMP-activated protein kinase (AMPK)
  • Autophagy
  • High glucose
  • Pancreatic β-cell

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Han, D., Yang, B., Olson, L. K., Greenstein, A., Baek, S. H., Claycombe, K. J., ... Kim, E. K. (2010). Activation of autophagy through modulation of 5′-AMP-activated protein kinase protects pancreatic β-cells from high glucose. Biochemical Journal, 425(3), 541-551. https://doi.org/10.1042/BJ20090429

Activation of autophagy through modulation of 5′-AMP-activated protein kinase protects pancreatic β-cells from high glucose. / Han, Diana; Yang, Byungho; Olson, L. Karl; Greenstein, Alexander; Baek, Seung Hoon; Claycombe, Kate J.; Goudreau, John L.; Yu, Seong Woon; Kim, Eun Kyoung.

In: Biochemical Journal, Vol. 425, No. 3, 01.02.2010, p. 541-551.

Research output: Contribution to journalArticle

Han, D, Yang, B, Olson, LK, Greenstein, A, Baek, SH, Claycombe, KJ, Goudreau, JL, Yu, SW & Kim, EK 2010, 'Activation of autophagy through modulation of 5′-AMP-activated protein kinase protects pancreatic β-cells from high glucose', Biochemical Journal, vol. 425, no. 3, pp. 541-551. https://doi.org/10.1042/BJ20090429
Han, Diana ; Yang, Byungho ; Olson, L. Karl ; Greenstein, Alexander ; Baek, Seung Hoon ; Claycombe, Kate J. ; Goudreau, John L. ; Yu, Seong Woon ; Kim, Eun Kyoung. / Activation of autophagy through modulation of 5′-AMP-activated protein kinase protects pancreatic β-cells from high glucose. In: Biochemical Journal. 2010 ; Vol. 425, No. 3. pp. 541-551.
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