Taurine supplementation induces long-term beneficial effects on glucose homeostasis in ob/ob mice
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The sulfur-containing amino acid, taurine (Tau), regulates glucose and lipid homeostasis under normal, pre- and diabetic conditions. Here, we aimed to verify whether Tau supplementation exerts its beneficial effects against obesity, hyperglycemia and alterations in islet functions, in leptin-deficient obese (ob/ob), over a long period of treatment. From weaning until 12 months of age, female ob/ob mice received, or not, 5% Tau in drinking water (obTau group). After this period, a reduction in hypertriglyceridemia and an improvement in glucose tolerance and insulin sensitivity were observed in obTau mice. In addition, the daily metabolic flexibility was restored in obTau mice. In the gastrocnemius muscle of obTau mice, the activation of AMP-activated protein kinase (AMPK) was increased, while total AMPK protein content was reduced. Finally, isolated islets from obTau mice expressed high amounts of pyruvate carboxylase (PC) protein and lower glucose-induced insulin secretion. Taking these evidences together Tau supplementation had long-term positive actions on glucose tolerance and insulin sensitivity, associated with a reduction in glucose-stimulated insulin secretion, in ob/ob mice. The improvement in insulin actions in obTau mice was due, at least in part, to increased activation of AMPK in skeletal muscle, while the increased content of the PC enzyme in pancreatic islets may help to preserve glucose responsiveness in obTau islets, possibly contributing to islet cell survive.
KeywordsAging AMP-activated protein Insulin secretion Metabolic flexibility ob/ob mice Pyruvate carboxylase
The authors thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq) for supporting the research. The authors also thank Marise Carnelossi Brunelli for excellent technical assistance and Nicola Conran for editing English.
PCB, RAR, ECM designed research; PCB, TMB, JFV, RCSB, JCSS, VYN conducted the experiments and acquired data; PCB, RAR analyzed data and performed statistical analysis; ACB, EMC acquired the reagents; PCB, RAR wrote the manuscript; JFV, ACB, EMC revised the manuscript; PCB, RAR, EMC had responsibility for final content.
This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/01717-9; 2015/12611-0), Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq 449794/2014-8).
Compliance with ethical standards
Conflict of interest
All contributing authors declare no conflicts of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- Batista TM, Ribeiro RA, da Silva PM, Camargo RL, Lollo PC, Boschero AC, Carneiro EM (2013) Taurine supplementation improves liver glucose control in normal protein and malnourished mice fed a high-fat diet. Mol Nutr Food Res 57:423–434. https://doi.org/10.1002/mnfr.201200345 CrossRefPubMedGoogle Scholar
- Lee JH et al (2014) Toxicity generated through inhibition of pyruvate carboxylase and carnitine palmitoyl transferase-1 is similar to high glucose/palmitate-induced glucolipotoxicity in INS-1 beta cells. Mol Cell Endocrinol 383:48–59. https://doi.org/10.1016/j.mce.2013.12.002 CrossRefPubMedGoogle Scholar
- Ribeiro RA, Vanzela EC, Oliveira CA, Bonfleur ML, Boschero AC, Carneiro EM (2010) Taurine supplementation: involvement of cholinergic/phospholipase C and protein kinase A pathways in potentiation of insulin secretion and Ca2 + handling in mouse pancreatic islets. Br J Nutr 104:1148–1155. https://doi.org/10.1017/S0007114510001820 CrossRefPubMedGoogle Scholar
- Ribeiro RA, Santos-Silva JC, Vettorazzi JF, Cotrim BB, Mobiolli DD, Boschero AC, Carneiro EM (2012) Taurine supplementation prevents morpho-physiological alterations in high-fat diet mice pancreatic beta-cells. Amino Acids 43:1791–1801. https://doi.org/10.1007/s00726-012-1263-5 CrossRefPubMedGoogle Scholar