Activation of melatonin signaling promotes β-cell survival and function

Safia Costes, Marti Boss, Anthony P. Thomas, Aleksey V. Matveyenko

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by pancreatic islet failure due to loss of β-cell secretory function and mass. Studies have identified a link between a variance in the gene encoding melatonin (MT) receptor 2, T2DM, and impaired insulin secretion. This genetic linkage raises the question whether MT signaling plays a role in regulation of β-cell function and survival in T2DM. To address this postulate, we used INS 832/13 cells to test whether activation of MT signaling attenuates proteotoxicity-induced β-cell apoptosis and through which molecular mechanism. We also used nondiabetic and T2DM human islets to test the potential of MT signaling to attenuate deleterious effects of glucotoxicity and T2DM on β-cell function. MT signaling in β-cells (with duration designed to mimic typical nightly exposure) significantly enhanced activation of the cAMP-dependent signal transduction pathway and attenuated proteotoxicity-induced β-cell apoptosis evidenced by reduced caspase-3 cleavage (~40%), decreased activation of stress-activated protein kinase/Jun-amino-terminal kinase (~50%) and diminished oxidative stress response. Activation of MT signaling in human islets was shown to restore glucose-stimulated insulin secretion in islets exposed to chronic hyperglycemia as well as in T2DM islets. Our data suggest that β-cell MT signaling is important for the regulation of β-cell survival and function and implies a preventative and therapeutic potential for preservation of β-cell mass and function in T2DM.

Original languageEnglish (US)
Pages (from-to)682-692
Number of pages11
JournalMolecular Endocrinology
Volume29
Issue number5
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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