Taurine supplementation modulates glucose homeostasis and islet function Everardo M. Carneiro a , Marcia Q. Latorraca b , Eliana Araujo c , Marta Beltrá d , Maria J. Oliveras e , Mónica Navarro f , Genoveva Berná f , Francisco J. Bedoya f , Licio A. Velloso c , Bernat Soria f , Franz Martín f, a Department of Physiology and Biophysic, Institute of Biology, State University of Campinas, Campinas, 13083-862 Brasil b Department of Food and Nutrition, School of Nutrition, University of Mato Groso, Cuiabá, 78060-900 Brasil c Faculty of Medical Sciences, Department of Internal Medicine, State University of Campinas, 13083-862 Campinas, Brasil d Institute of Bioengineering, University Miguel Hernández, Alicante, 03202 Spain e Department of Nutrition and Bromatology, School of Pharmacy, University of Granada, Granada, 18071 Spain f Andalusian Center for Molecular Biology and Regenerative Medicine, University Pablo Olavide, CIBERDEM, 41092 Seville, Spain Received 21 January 2008; received in revised form 23 April 2008; accepted 7 May 2008 Abstract Taurine is a conditionally essential amino acid for human that is involved in the control of glucose homeostasis; however, the mechanisms by which the amino acid affects blood glucose levels are unknown. Using an animal model, we have studied these mechanisms. Mice were supplemented with taurine for 30 d. Blood glucose homeostasis was assessed by intraperitoneal glucose tolerance tests (IPGTT). Islet cell function was determined by insulin secretion, cytosolic Ca 2+ measurements and glucose metabolism from isolated islets. Islet cell gene expression and translocation was examined via immunohistochemistry and quantitative real-time polymerase chain reaction. Insulin signaling was studied by Western blot. Islets from taurine-supplemented mice had: (i) significantly higher insulin content, (ii) increased insulin secretion at stimulatory glucose concentrations, (iii) significantly displaced the dose-response curve for glucose-induced insulin release to the left, (iv) increased glucose metabolism at 5·6 and 11·1-mmol/L concentrations; (v) slowed cytosolic Ca 2+ concentration ([Ca 2+ ]i) oscillations in response to stimulatory glucose concentrations; (vi) increased insulin, sulfonylurea receptor-1, glucokinase, Glut-2, proconvertase and pancreas duodenum homeobox-1 (PDX-1) gene expression and (vii) increased PDX-1 expression in the nucleus. Moreover, taurine supplementation significantly increased both basal and insulin stimulated tyrosine phosphorylation of the insulin receptor in skeletal muscle and liver tissues. Finally, taurine supplemented mice showed an improved IPGTT. These results indicate that taurine controls glucose homeostasis by regulating the expression of genes required for glucose-stimulated insulin secretion. In addition, taurine enhances peripheral insulin sensitivity. © 2009 Elsevier Inc. All rights reserved. Keywords: Diabetes; Insulin sensitivity; Blood glucose homeostasis; Amino acids 1. Introduction Amino acids have been recognized as important signaling mediators in different cellular functions. Taurine (2-amino ethane sulphonic acid) is a conditionally essential amino acid for human and nonhuman primates [1], that is involved in many important biological functions including osmoregula- tion, inhibition of protein phosphorylation and calcium modulation [2,3]. Taurine is found at high concentrations within pancreatic islets [4]. Taurine reduces the rate of apoptosis [5] and acts on DNA synthesis, preventing abnormal development of the endocrine pancreas [6]. Previous reports have dealt with its effects on insulin secretion. In fetal rat islets, taurine increases glucose-stimulated insulin secretion and enhances Available online at www.sciencedirect.com Journal of Nutritional Biochemistry 20 (2009) 503 511 Grants, sponsors and funding sources: The present study was supported by Ministry of Education and Science (SAF2003-03307; SAF2003-0367; SAF2006-06673; SAF2006-13686-C02-01); Instituto de Salud Carlos III (RCMN C03/08; ISCIII-RETIC RD06/0015; CIBERDEM) and CNP-Q-Brazil-2000-01/03-5. Corresponding author. Tel.: +34 954 97 79 44; fax: +34 954 34 98 13. E-mail address: fmarber@upo.es (F. Martín). 0955-2863/$ see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jnutbio.2008.05.008