Functional and structural adaptations in the pancreatic α-cell and changes in glucagon signaling during protein malnutrition

Endocrinology
Laura MarroquíIvan Quesada

Abstract

Chronic malnutrition leads to multiple changes in β-cell function and peripheral insulin actions to adapt glucose homeostasis to these restricted conditions. However, despite glucose homeostasis also depends on glucagon effects, the role of α-cells in malnutrition is largely unknown. Here, we studied α-cell function and hepatic glucagon signaling in mice fed with low-protein (LP) or normal-protein diet for 8 wk after weaning. Using confocal microscopy, we found that inhibition of Ca²⁺ signaling by glucose was impaired in α-cells of LP mice. Consistent with these findings, the ability of glucose to inhibit glucagon release in isolated islets was also diminished in LP mice. This altered secretion was not related with changes in either glucagon gene expression or glucagon content. A morphometric analysis showed that α-cell mass was significantly increased in malnourished animals, aspect that was probably related with their enhanced plasma glucagon levels. When we analyzed the hepatic function, we observed that the phosphorylation of protein kinase A and cAMP response-binding element protein in response to fasting or exogenous glucagon was impaired in LP mice. Additionally, the up-regulated gene expression in response to fasting ob...Continue Reading

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Citations

Oct 2, 2015·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Mário Cesar do Nascimento BevilaquaKarin C Calaza
Feb 26, 2015·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·C LubaczeuskiM L Bonfleur
Mar 7, 2014·MBio·Danielle HickmanStephanie M Karst
Oct 15, 2018·Journal of Cellular Physiology·Thiago R AraujoRosane Aparecida Ribeiro

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