AMPK profiling in rodent and human pancreatic beta-cells under nutrient-rich metabolic stress

Thierry Brun*, Cecilia Jiménez-Sánchez*, Jesper Grud Skat Madsen*, Noushin Hadadi*, Dominique Duhamel*, Clarissa Bartley*, Lucie Oberhauser*, Mirko Trajkovski*, Susanne Mandrup*, Pierre Maechler*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Chronic exposure of pancreatic β-cells to elevated nutrient levels impairs their function and potentially induces apoptosis. Like in other cell types, AMPK is activated in β-cells under conditions of nutrient deprivation, while little is known on AMPK responses to metabolic stresses. Here, we first reviewed recent studies on the role of AMPK activation in β-cells. Then, we investigated the expression profile of AMPK pathways in β-cells following metabolic stresses. INS-1E β-cells and human islets were exposed for 3 days to glucose (5.5–25 mM), palmitate or oleate (0.4 mM), and fructose (5.5 mM). Following these treatments, we analyzed transcript levels of INS-1E β-cells by qRT-PCR and of human islets by RNA-Seq; with a special focus on AMPK-associated genes, such as the AMPK catalytic subunits α1 (Prkaa1) and α2 (Prkaa2). AMPKα and pAMPKα were also evaluated at the protein level by immunoblotting. Chronic exposure to the different metabolic stresses, known to alter glucose-stimulated insulin secretion, did not change AMPK expression, either in insulinoma cells or in human islets. Expression profile of the six AMPK subunits was marginally modified by the different diabetogenic conditions. However, the expression of some upstream kinases and downstream AMPK targets, including K-ATP channel subunits, exhibited stress-specific signatures. Interestingly, at the protein level, chronic fructose treatment favored fasting-like phenotype in human islets, as witnessed by AMPK activation. Collectively, previously published and present data indicate that, in the β-cell, AMPK activation might be implicated in the pre-diabetic state, potentially as a protective mechanism.

Original languageEnglish
Article number3982
JournalInternational Journal of Molecular Sciences
Volume21
Issue number11
Number of pages16
ISSN1661-6596
DOIs
Publication statusPublished - 2020

Keywords

  • AMPK
  • ATP
  • Beta-cell
  • Fructose
  • Glucotoxicity
  • Insulin
  • Pancreatic islets

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    Brun, T., Jiménez-Sánchez, C., Madsen, J. G. S., Hadadi, N., Duhamel, D., Bartley, C., Oberhauser, L., Trajkovski, M., Mandrup, S., & Maechler, P. (2020). AMPK profiling in rodent and human pancreatic beta-cells under nutrient-rich metabolic stress. International Journal of Molecular Sciences , 21(11), [3982]. https://doi.org/10.3390/ijms21113982