Oncotarget

Research Papers:

Insulin-like growth factor-1 is a negative modulator of glucagon secretion

Elettra Mancuso, Gaia C. Mannino, Concetta Di Fatta, Anastasia Fuoco, Rosangela Spiga, Francesco Andreozzi _ and Giorgio Sesti

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Oncotarget. 2017; 8:51719-51732. https://doi.org/10.18632/oncotarget.18514

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Abstract

Elettra Mancuso1,*, Gaia C. Mannino1,*, Concetta Di Fatta1, Anastasia Fuoco1, Rosangela Spiga1, Francesco Andreozzi1 and Giorgio Sesti1

1Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy

*These authors have contributed equally to this work

Correspondence to:

Francesco Andreozzi, email: andreozzif@unicz.it

Keywords: glucagon, IGF-1

Abbreviations: IGF-1: insulin-like growth factor-1; Hb: hemoglobin; BMI: body mass index; HbA1c: glycated hemoglobin; HOMA index: homeostasis model assessment index

Received: January 28, 2017     Accepted: May 01, 2017     Published: June 16, 2017

ABSTRACT

Glucagon secretion involves a combination of paracrine, autocrine, hormonal, and autonomic neural mechanisms. Type 2 diabetes often presents impaired glucagon suppression by insulin and glucose. Insulin-like growth factor-I (IGF-1) has elevated homology with insulin, and regulates pancreatic β-cells insulin secretion. Insulin and IGF-1 receptors share considerable structure homology and function. We hypothesized the existence of a mechanism linking the inhibition of α-cells glucagon secretion to IGF-1. Herein, we evaluated the association between plasma IGF-1 and glucagon levels in 116 nondiabetic adults. After adjusting for age gender and BMI, fasting glucagon levels were positively correlated with 2-h post-load glycaemia, HOMA index and fasting insulin, and were negatively correlated with IGF-1 levels. In a multivariable regression, the variables independently associated to fasting glucagon were circulating IGF-1 levels, HOMA index and BMI, explaining 20.7% variation. To unravel the molecular mechanisms beneath IGF-1 and glucagon association, we investigated whether IGF-1 directly modulates glucagon expression and secretion in an in vitro model of α-cells. Our data showed that IGF-1 inhibits the ability of low glucose concentration to stimulate glucagon expression and secretion via activation of the phosphatidylinositol-3-kinase/Akt/FoxO1 pathway.

Collectively, our results suggest a new regulatory role of IGF-1 on α-cells biological function.


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