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Endogenous α2A-Adrenoceptor-Operated Sympathoadrenergic Tones Attenuate Insulin Secretion via cAMP/TRPM2 Signaling

Kiyonori Ito1, Katsuya Dezaki2, Masashi Yoshida1

  • 1First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan.

Diabetes
|December 29, 2016
PubMed

Insights

Physiological adrenaline suppresses insulin release by activating α2A-adrenoceptors and TRPM2 channels in pancreatic beta cells. This pathway offers a potential therapeutic target for type 2 diabetes treatment.

Area of Science:

  • Endocrinology
  • Cell Physiology
  • Molecular Pharmacology

Background:

  • Adrenaline's role in physiological insulin regulation by pancreatic beta cells is poorly understood.
  • Nonselective cation channels (NSCCs) are implicated in glucose-induced insulin secretion.
  • Transient Receptor Potential Melastatin 2 (TRPM2) is a type of NSCC found in beta cells.

Purpose of the Study:

  • To investigate if physiological adrenaline action in beta cells is mediated by the TRPM2 channel.
  • To elucidate the signaling pathway linking adrenergic stimulation to insulin secretion inhibition.

Main Methods:

  • Electrophysiological recordings of NSCCs current in beta cells.
  • Measurement of cAMP production and insulin secretion in response to glucose and incretins.
  • Experiments using wild-type and TRPM2-knockout mice.
  • Assessment of glucose tolerance in vivo.

Main Results:

  • Physiological adrenaline suppressed glucose- and incretin-stimulated insulin secretion and cAMP production in wild-type mice.
  • Adrenaline inhibited NSCCs current and reduced beta cell membrane excitability via α2A-adrenoceptors.
  • TRPM2-knockout mice showed no suppression of insulin secretion by adrenaline.
  • α2A-adrenoceptor antagonist yohimbine improved glucose tolerance in wild-type but not TRPM2-knockout mice.

Conclusions:

  • Physiological adrenaline inhibits insulin release through a pathway involving α2A-adrenoceptor, cAMP, and TRPM2 channels in pancreatic beta cells.
  • This signaling axis represents a potential therapeutic target for managing type 2 diabetes.

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