Abstract
Malnutrition programs metabolism, favor dysfunction of β cells. We aimed to establish an in vitro protocol of malnutrition, assessing the effect of amino acid restriction upon the β cells. Insulin-producing cells INS-1E and pancreatic islets were maintained in RPMI 1640 medium containing 1× (Ctl) or 0.25× (AaR) of amino acids. We evaluated several markers of β-cell function and viability. AaR Insulin secretion was reduced, whereas cell viability was unaltered. Calcium oscillations in response to glucose increased in AaR. AaR showed lower Ins1 RNAm, snap 25, and PKC (protein kinase C) protein content, whereas phospho-eIF2α was increased. AaR cells exposed to nutrient or chemical challenges displayed higher apoptosis rates. We showed that amino acid restriction programmed β cell and induced functional changes. This model might be useful for the study of molecular mechanisms involved with β-cell programming helping to establish novel therapeutic targets to prevent harmful outcomes of malnutrition.
References
Jul 1, 1992·Diabetologia·C N Hales, D J Barker
Nov 1, 1981·Diabetologia·A M ScottE Rojas
Feb 5, 1998·Lancet·A C RavelliO P Bleker
Sep 7, 2002·Molecular and Cellular Biology·Peichuan ZhangDouglas R Cavener
Oct 9, 2002·Trends in Endocrinology and Metabolism : TEM·Susan E Ozanne, C Nicholas Hales
Dec 13, 2005·The International Journal of Biochemistry & Cell Biology·Brigitte Reusens, Claude Remacle
Oct 25, 2007·Biochemical Society Transactions·P NewsholmeL Brennan
Dec 13, 2007·Jornal de pediatria·Patrícia P SilveiraMarco A Barbieri
Feb 25, 2010·Science Signaling·Decio L Eizirik, Miriam Cnop
Jun 18, 2010·Endocrinology·Sergi SorianoIvan Quesada
Aug 17, 2010·Amino Acids·Camila Aparecida Machado de OliveiraEverardo Magalhães Carneiro
May 6, 2011·The Journal of Nutritional Biochemistry·Thiago M BatistaEverardo M Carneiro
Apr 6, 2012·The British Journal of Nutrition·Letícia Martins Ignácio-SouzaMárcia Queiroz Latorraca
May 29, 2014·Amino Acids·Jean F VettorazziEverardo M Carneiro
Nov 21, 2014·Journal of Diabetes Investigation·Søs Skovsø
Apr 14, 2016·The Journal of Endocrinology·Kaiyuan YangCatherine B Chan
Sep 17, 2016·Scientific Reports·Nayara Carvalho LeiteEverardo Magalhães Carneiro
Aug 16, 2017·The Journal of Endocrinology·Brit H BoehmerPaul J Rozance
Sep 28, 2017·Molecular Metabolism·Miriam CnopParaskevi Salpea