5'-AMP-activated protein kinase controls insulin-containing secretory vesicle dynamics

Takashi Tsuboi, Gabriela da Silva Xavier, Isabelle Leclerc, Guy A Rutter

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83 Citations (Scopus)


Changes in 5′-AMP-activated protein kinase (AMPK) activity have recently been implicated in the control of insulin secretion by glucose (da Silva Xavier, G., Leclerc, I., Varadi, A., Tsuboi, T., Moule, S. K., and Rutter, G. A. (2003) Biochem. J. 371, 761–774). Here, we examine the possibility that activation of AMPK may regulate distal steps in insulin secretion, including vesicle movement and fusion with the plasma membrane. Vesicle dynamics were imaged in single pancreatic MIN6 β-cells expressing lumen-targeted pH-insensitive yellow fluorescent protein, neuropeptide Y.Venus, or monomeric red fluorescent protein by total internal reflection fluorescence and Nipkow disc confocal microscopy. Overexpression of a truncated, constitutively active form of AMPK (AMPKα1, 1–312, T172D; AMPK CA), inhibited glucose-stimulated (30 versus 3.0 mM) vesicle movements, and decreased the number of vesicles docked or fusing at the plasma membrane, while having no effect on the kinetics of individual secretory events. Expression of the activated form of AMPK also prevented dispersal of the cortical actin network at high glucose concentrations. Monitored in permeabilized cells, where the effects of AMPK CA on glucose metabolism and ATP synthesis were bypassed, AMPK CA inhibited Ca2+ and ATP-induced insulin secretion, and decreased ATP-dependent vesicle movements. These findings suggest that components of the vesicle transport network, including vesicle-associated motor proteins, may be targets of AMPK in β-cells, dephosphorylation of which is required for vesicle mobilization at elevated glucose concentrations.

Original languageEnglish
Pages (from-to)52042-52051
Number of pages10
JournalJournal of Biological Chemistry
Issue number52
Publication statusPublished - 26 Dec 2003


  • AMP-Activated Protein Kinases
  • Actins/metabolism
  • Adenosine Triphosphate/metabolism
  • Adenoviridae/genetics
  • Animals
  • Binding Sites
  • Calcium/metabolism
  • Cell Membrane/metabolism
  • Digitonin/metabolism
  • Dose-Response Relationship, Drug
  • Glucose/metabolism
  • Hydrogen-Ion Concentration
  • Immunohistochemistry
  • Insulin/metabolism
  • Islets of Langerhans/metabolism
  • Kinetics
  • Luminescent Proteins/metabolism
  • Magnesium/metabolism
  • Mice
  • Microscopy, Confocal
  • Models, Statistical
  • Multienzyme Complexes/physiology
  • Phosphorylation
  • Plasmids/metabolism
  • Protein-Serine-Threonine Kinases/physiology
  • Secretory Vesicles/metabolism
  • Time Factors
  • Tubulin/metabolism


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