Alessandro Ustione
Last active: 5/12/2015

Neuropeptide Y and somatostatin inhibit insulin secretion through different mechanisms.

Schwetz TA, Ustione A, Piston DW
Am J Physiol Endocrinol Metab. 2013 304 (2): E211-21

PMID: 23211512 · PMCID: PMC3543566 · DOI:10.1152/ajpendo.00374.2012

Pancreatic β-cells regulate glucose homeostasis by secreting insulin in response to glucose elevation and G protein-coupled receptor (GPCR) activation. Neuropeptide Y (NPY) and somatostatin (SST) attenuate insulin secretion through G(i) activation of Y(1) and SSTR(1&5) receptors, respectively. The downstream pathways altered by NPY and SST are poorly understood. Thus, we investigated these underlying mechanisms. NPY and SST increase cellular redox potential, suggesting that their inhibitory effect may not be mediated through metabolic inhibition. NPY does not affect intracellular calcium ([Ca(2+)](i)) activity upon glucose stimulation, whereas SST alters this response. G(βγ)-subunit inhibition by gallein attenuates insulin secretion but does not alter metabolism or [Ca(2+)](i). mSIRK-induced G(βγ) activation does not modulate glucose metabolism but increases [Ca(2+)](i) activity and potentiates insulin release. Cotreatment with gallein and NPY or SST reduces insulin secretion to levels similar to that of gallein alone. mSIRK and NPY cotreatment potentiates insulin secretion similarly to mSIRK alone, whereas mSIRK and SST treatment decreases insulin release. The data support a model where SST attenuates secretion through G(βγ) inhibition of Ca(2+) activity, while NPY activates a Ca(2+)-independent pathway mediated by G(α). GPCR ligands signal through multiple pathways to inhibit insulin secretion, and determining these mechanisms could lead to novel diabetic therapies.

MeSH Terms (16)

Animals Calcium Signaling Cells, Cultured Down-Regulation Drug Evaluation, Preclinical Glucose Insulin Insulin-Secreting Cells Insulin Secretion Islets of Langerhans Mice Mice, Inbred C57BL Neuropeptide Y Secretory Pathway Somatostatin Time Factors

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