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Metabolic regulation, and insulin secretion and action mechanism induced by L-glutamine supplementation in mutant obese mice

Grant number: 15/00446-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2015
Effective date (End): September 30, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Angelo Rafael Carpinelli
Grantee:Vinicius Fernandes Cruzat
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/08769-1 - The role of NAD(P)H oxidase in the physiological and pathological molecular mechanisms of insulin secreting cells, AP.TEM


Obesity-associated diabetes is increasing all over the world. Glucose and lipids concentration, metabolism and signaling pathways are well studied in the context of diabetes, however less is known about the metabolism of amino acids and signaling pathways involving in insulin secretion and a possible relationship with the NAD(P)H oxidase complex. The concentration of the most abundant amino acid in the body, glutamine may be reduced in diabetes, which affect the intermediary metabolism and the insulin secretion and action. Previous studies have shown antioxidant effects mediated through the glutathione (GSH) system, Heat Shock Proteins (HSP) and anti-inflammatory effects of glutamine. Despite of this, it is unknown whether these effects can be obtained in obesity-associated diabetes. Thus, the hypothesis of the present study is based on the fact that glutamine availability through the oral supplementation can increase cell protection, at the central (pancreatic beta cells) and peripheral level, attenuating insulin resistance during the progression of insulin resistance and action. Glutamine may be a possible adjuvant therapy to reduce the risk of type 2 diabetes progression, improving insulin sensitivity through intracellular mechanisms related to protection, such as HSP and GSH, attenuating the oxidative stress via NAD(P)H oxidase complex. To test this hypothesis mutant obese ob/ob mice C57/BL6 with insulin resistance will be supplemented with L-glutamine.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RAIZEL, RAQUEL; MOREIRA LEITE, JAQUELINE SANTOS; HYPOLITO, THAIS MENEZES; COQUEIRO, AUDREY YULE; NEWSHOLME, PHILIP; CRUZAT, VINICIUS FERNANDES; TIRAPEGUI, JULIO. Determination of the anti-inflammatory and cytoprotective effects of L-glutamine and L-alanine, or dipeptide, supplementation in rats submitted to resistance exercise. BRITISH JOURNAL OF NUTRITION, v. 116, n. 3, p. 470-479, AUG 14 2016. Web of Science Citations: 10.
MOREIRA LEITE, JAQUELINE SANTOS; RAIZEL, RAQUEL; HYPOLITO, THAIS MENEZES; ROSA, THIAGO DOS SANTOS; CRUZAT, VINICIUS FERNANDES; TIRAPEGUI, JULIO. L-glutamine and L-alanine supplementation increase glutamine-glutathione axis and muscle HSP-27 in rats trained using a progressive high-intensity resistance exercise. APPLIED PHYSIOLOGY NUTRITION AND METABOLISM, v. 41, n. 8, p. 842-849, AUG 2016. Web of Science Citations: 9.
VERDILE, GIUSEPPE; KEANE, KEVIN N.; CRUZAT, VINICIUS F.; MEDIC, SANDRA; SABALE, MIHEER; ROWLES, JOANNE; WIJESEKARA, NADEEJA; MARTINS, RALPH N.; FRASER, PAUL E.; NEWSHOLME, PHILIP. Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer's Disease. Mediators of Inflammation, 2015. Web of Science Citations: 82.

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