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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

Adrenaline Stimulates Glucagon Secretion by Tpc2-Dependent Ca2+ Mobilization From Acidic Stores in Pancreatic α-Cells


  • Alexander Hamilton
  • Quan Zhang
  • Albert Salehi
  • Mara Willems
  • Jakob G Knudsen
  • Anna K Ringgaard
  • Caroline E Chapman
  • Alejandro Gonzalez-Alvarez
  • Nicoletta C Surdo
  • Manuela Zaccolo
  • Davide Basco
  • Paul R V Johnson
  • Reshma Ramracheya
  • Guy A Rutter
  • Antony Galione
  • Patrik Rorsman
  • Andrei I Tarasov

Summary, in English

Adrenaline is a powerful stimulus of glucagon secretion. It acts by activation of β-adrenergic receptors, but the downstream mechanisms have only been partially elucidated. Here, we have examined the effects of adrenaline in mouse and human α-cells by a combination of electrophysiology, imaging of Ca2+ and PKA activity, and hormone release measurements. We found that stimulation of glucagon secretion correlated with a PKA- and EPAC2-dependent (inhibited by PKI and ESI-05, respectively) elevation of [Ca2+]i in α-cells, which occurred without stimulation of electrical activity and persisted in the absence of extracellular Ca2+ but was sensitive to ryanodine, bafilomycin, and thapsigargin. Adrenaline also increased [Ca2+]i in α-cells in human islets. Genetic or pharmacological inhibition of the Tpc2 channel (that mediates Ca2+ release from acidic intracellular stores) abolished the stimulatory effect of adrenaline on glucagon secretion and reduced the elevation of [Ca2+]i Furthermore, in Tpc2-deficient islets, ryanodine exerted no additive inhibitory effect. These data suggest that β-adrenergic stimulation of glucagon secretion is controlled by a hierarchy of [Ca2+]i signaling in the α-cell that is initiated by cAMP-induced Tpc2-dependent Ca2+ release from the acidic stores and further amplified by Ca2+-induced Ca2+ release from the sarco/endoplasmic reticulum.


  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year












Document type

Journal article


American Diabetes Association Inc.


  • Cell and Molecular Biology


  • Adrenergic Neurons/cytology
  • Animals
  • Animals, Outbred Strains
  • Calcium Channels/chemistry
  • Calcium Signaling/drug effects
  • Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors
  • Endoplasmic Reticulum/drug effects
  • Enzyme Inhibitors/pharmacology
  • Epinephrine/metabolism
  • Glucagon/metabolism
  • Glucagon-Secreting Cells/cytology
  • Guanine Nucleotide Exchange Factors/antagonists & inhibitors
  • Humans
  • Membrane Transport Modulators/pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pancreas/drug effects
  • Patch-Clamp Techniques
  • Sarcoplasmic Reticulum/drug effects
  • Tissue Culture Techniques
  • Up-Regulation/drug effects




  • ISSN: 1939-327X