Amino Acids

, Volume 46, Issue 9, pp 2123–2136 | Cite as

Taurine supplementation increases KATP channel protein content, improving Ca2+ handling and insulin secretion in islets from malnourished mice fed on a high-fat diet

  • Jean F. Vettorazzi
  • Rosane A. Ribeiro
  • Junia C. Santos-Silva
  • Patricia C. Borck
  • Thiago M. Batista
  • Tarlliza R. Nardelli
  • Antonio C. Boschero
  • Everardo M. Carneiro
Original Article

Abstract

Pancreatic β-cells are highly sensitive to suboptimal or excess nutrients, as occurs in protein-malnutrition and obesity. Taurine (Tau) improves insulin secretion in response to nutrients and depolarizing agents. Here, we assessed the expression and function of Cav and KATP channels in islets from malnourished mice fed on a high-fat diet (HFD) and supplemented with Tau. Weaned mice received a normal (C) or a low-protein diet (R) for 6 weeks. Half of each group were fed a HFD for 8 weeks without (CH, RH) or with 5 % Tau since weaning (CHT, RHT). Isolated islets from R mice showed lower insulin release with glucose and depolarizing stimuli. In CH islets, insulin secretion was increased and this was associated with enhanced KATP inhibition and Cav activity. RH islets secreted less insulin at high K+ concentration and showed enhanced KATP activity. Tau supplementation normalized K+-induced secretion and enhanced glucose-induced Ca2+ influx in RHT islets. R islets presented lower Ca2+ influx in response to tolbutamide, and higher protein content and activity of the Kir6.2 subunit of the KATP. Tau increased the protein content of the α1.2 subunit of the Cav channels and the SNARE proteins SNAP-25 and Synt-1 in CHT islets, whereas in RHT, Kir6.2 and Synt-1 proteins were increased. In conclusion, impaired islet function in R islets is related to higher content and activity of the KATP channels. Tau treatment enhanced RHT islet secretory capacity by improving the protein expression and inhibition of the KATP channels and enhancing Synt-1 islet content.

Keywords

High-fat diet Insulin secretion KATP channels Protein malnutrition Taurine supplementation Voltage-sensitive Ca2+ channels 

Abbreviations

AUC

Area under curve

BSA

Bovine serum albumin

BW

Body weight

C

Control

Cav

Voltage-sensitive Ca2+ channel

Cavα1.2

α1.2 subunit of the Cav

Cavβ2

β2 subunit of the Cav

[Ca2+]i

Intracellular Ca2+ concentration

CH

Control mice submitted to HFD

CHOL

Cholesterol

CHT

CH supplemented with Tau

DZX

Diazoxide

FAs

Fatty acids

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

GLUT-2

Glucose transporter 2

HFD

High-fat diet

ipGTT

Intraperitoneal glucose tolerance test

ipITT

Intraperitoneal insulin tolerance test

KATP

ATP-sensitive K+

KBB

Krebs–bicarbonate buffer

Kir6.2

Subunit 6.2 of the inward-rectifier K+ channel

Nif

Nifedipine

PK

Protein kinase

R

Protein-restricted mice

RH

R submitted to HFD

RHT

RH mice supplemented with Tau

RIA

Radioimmunoassay

SNAP-25

Synaptosomal associated protein of 25 kDa

SNARE

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

Synt-1

Syntaxin 1

SUR1

Sulfonylurea receptor 1

Tau

Taurine

Tolb

Tolbutamide

TG

Triglycerides

Notes

Acknowledgments

This study is part of the M.Sc Thesis of Jean Franciesco Vettorazzi and was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq); Instituto Nacional de Obesidade e Diabetes (CNPq/FAPESP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). We thank Nicola Conran for editing English.

Conflict of interest

All contributing authors report no conflicts of interest.

References

  1. Amaral AG, Rafacho A, Machado de Oliveira CA, Batista TM, Ribeiro RA, Latorraca MQ, Boschero AC, Carneiro EM (2010) Leucine supplementation augments insulin secretion in pancreatic islets of malnourished mice. Pancreas 39(6):847–855PubMedCrossRefGoogle Scholar
  2. Andersson SA, Olsson AH, Esguerra JL, Heimann E, Ladenvall C, Edlund A, Salehi A, Taneera J, Degerman E, Groop L, Ling C, Eliasson L (2012) Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes. Mol Cell Endocrinol 364(1–2):36–45PubMedCrossRefGoogle Scholar
  3. Araujo EP, De Souza CT, Ueno M, Cintra DE, Bertolo MB, Carvalheira JB, Saad MJ, Velloso LA (2007) Infliximab restores glucose homeostasis in an animal model of diet-induced obesity and diabetes. Endocrinology 148(12):5991–5997PubMedCrossRefGoogle Scholar
  4. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM (1993) Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36(1):62–67PubMedCrossRefGoogle Scholar
  5. Batista TM, Ribeiro RA, Amaral AG, de Oliveira CA, Boschero AC, Carneiro EM (2012) Taurine supplementation restores glucose and carbachol-induced insulin secretion in islets from low-protein diet rats: involvement of Ach-M3R, Synt 1 and SNAP-25 proteins. J Nutr Biochem 23(3):306–312PubMedCrossRefGoogle Scholar
  6. Batista TM, da Silva PM, Amaral AG, Ribeiro RA, Boschero AC, Carneiro EM (2013a) Taurine supplementation restores insulin secretion and reduces ER stress markers in protein-malnourished mice. Adv Exp Med Biol 776:129–139PubMedCrossRefGoogle Scholar
  7. Batista TM, Ribeiro RA, da Silva PM, Camargo RL, Lollo PC, Boschero AC, Carneiro EM (2013b) Taurine supplementation improves liver glucose control in normal protein and malnourished mice fed a high-fat diet. Mol Nutr Food Res 57(3):423–434. doi: 10.1002/mnfr.201200345 PubMedCrossRefGoogle Scholar
  8. Bernardis LL, Patterson BD (1968) Correlation between ‘Lee index’ and carcass fat content in weanling and adult female rats with hypothalamic lesions. J Endocrinol 40(4):527–528PubMedCrossRefGoogle Scholar
  9. Best L, Jarman E, Brown PD (2011) A dual action of saturated fatty acids on electrical activity in rat pancreatic beta-cells. Role of volume-regulated anion channel and KATP channel currents. J Physiol 589(Pt 6):1307–1316PubMedCentralPubMedCrossRefGoogle Scholar
  10. Bol VV, Delattre AI, Reusens B, Raes M, Remacle C (2009) Forced catch-up growth after fetal protein restriction alters the adipose tissue gene expression program leading to obesity in adult mice. Am J Physiol Regul Integr Comp Physiol 297(2):R291–R299. doi: 10.1152/ajpregu.90497.2008 PubMedCrossRefGoogle Scholar
  11. Boschero AC, Malaisse WJ (1979) Stimulus-secretion coupling of glucose-induced insulin release XXIX. Regulation of 86Rb + efflux from perfused islets. Am J Physiol 236(2):E139–E146PubMedGoogle Scholar
  12. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedCrossRefGoogle Scholar
  13. Branstrom R, Aspinwall CA, Valimaki S, Ostensson CG, Tibell A, Eckhard M, Brandhorst H, Corkey BE, Berggren PO, Larsson O (2004) Long-chain CoA esters activate human pancreatic beta-cell KATP channels: potential role in Type 2 diabetes. Diabetologia 47(2):277–283PubMedCrossRefGoogle Scholar
  14. Bustamante J, Lobo MV, Alonso FJ, Mukala NT, Gine E, Solis JM, Tamarit-Rodriguez J, Martin Del Rio R (2001) An osmotic-sensitive taurine pool is localized in rat pancreatic islet cells containing glucagon and somatostatin. Am J Physiol Endocrinol Metab 281(6):E1275–E1285PubMedGoogle Scholar
  15. Camargo RL, Batista TM, Ribeiro RA, Velloso LA, Boschero AC, Carneiro EM (2013) Effects of taurine supplementation upon food intake and central insulin signaling in malnourished mice fed on a high-fat diet. Adv Exp Med Biol 776:93–103. doi: 10.1007/978-1-4614-6093-0_10 PubMedCrossRefGoogle Scholar
  16. Carneiro EM, Latorraca MQ, Araujo E, Beltra M, Oliveras MJ, Navarro M, Berna G, Bedoya FJ, Velloso LA, Soria B, Martin F (2009) Taurine supplementation modulates glucose homeostasis and islet function. J Nutr Biochem 20(7):503–511PubMedCrossRefGoogle Scholar
  17. Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL (2005) Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes 54(Suppl 2):S97–S107PubMedCrossRefGoogle Scholar
  18. da Silva PM, Batista TM, Ribeiro RA, Zoppi CC, Boschero AC, Carneiro EM (2012) Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: effect of leucine supplementation. Metabolism 61(5):721–732PubMedCrossRefGoogle Scholar
  19. Delghingaro-Augusto V, Ferreira F, Bordin S, do Amaral ME, Toyama MH, Boschero AC, Carneiro EM (2004) A low protein diet alters gene expression in rat pancreatic islets. J Nutr 134(2):321–327PubMedGoogle Scholar
  20. Ferreira F, Filiputti E, Arantes VC, Stoppiglia LF, Araujo EP, Delghingaro-Augusto V, Latorraca MQ, Toyama MH, Boschero AC, Carneiro EM (2003) Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase calpha expression. J Nutr 133(3):695–699PubMedGoogle Scholar
  21. Ferreira F, Barbosa HC, Stoppiglia LF, Delghingaro-Augusto V, Pereira EA, Boschero AC, Carneiro EM (2004) Decreased insulin secretion in islets from rats fed a low protein diet is associated with a reduced PKAalpha expression. J Nutr 134(1):63–67PubMedGoogle Scholar
  22. Gribble FM, Reimann F (2002) Pharmacological modulation of K(ATP) channels. Biochem Soc Trans 30(2):333–339PubMedCrossRefGoogle Scholar
  23. Hales CN, Barker DJ (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35(7):595–601PubMedCrossRefGoogle Scholar
  24. Han J, Bae JH, Kim SY, Lee HY, Jang BC, Lee IK, Cho CH, Lim JG, Suh SI, Kwon TK, Park JW, Ryu SY, Ho WK, Earm YE, Song DK (2004) Taurine increases glucose sensitivity of UCP2-overexpressing beta-cells by ameliorating mitochondrial metabolism. Am J Physiol Endocrinol Metab 287(5):E1008–E1018PubMedCrossRefGoogle Scholar
  25. Hoppa MB, Collins S, Ramracheya R, Hodson L, Amisten S, Zhang Q, Johnson P, Ashcroft FM, Rorsman P (2009) Chronic palmitate exposure inhibits insulin secretion by dissociation of Ca(2 +) channels from secretory granules. Cell Metab 10(6):455–465PubMedCentralPubMedCrossRefGoogle Scholar
  26. Iwashima Y, Abiko A, Ushikubi F, Hata A, Kaku K, Sano H, Eto M (2001) Downregulation of the voltage-dependent calcium channel (VDCC) beta-subunit mRNAs in pancreatic islets of type 2 diabetic rats. Biochem Biophys Res Commun 280(3):923–932PubMedCrossRefGoogle Scholar
  27. Lee SH, Lee HY, Kim SY, Lee IK, Song DK (2004) Enhancing effect of taurine on glucose response in UCP2-overexpressing beta cells. Diabetes Res Clin Pract 66(Suppl 1):S69–S74PubMedGoogle Scholar
  28. Lim JG, Lee HY, Yun JE, Kim SP, Park JW, Suh SI, Jang BC, Cho CH, Bae JH, Kim SS, Han J, Park MJ, Song DK (2004) Taurine block of cloned ATP-sensitive K + channels with different sulfonylurea receptor subunits expressed in Xenopus laevis oocytes. Biochem Pharmacol 68(5):901–910PubMedCrossRefGoogle Scholar
  29. Moritz W, Leech CA, Ferrer J, Habener JF (2001) Regulated expression of adenosine triphosphate-sensitive potassium channel subunits in pancreatic beta-cells. Endocrinology 142(1):129–138PubMedGoogle Scholar
  30. Nagamatsu S, Nakamichi Y, Yamamura C, Matsushima S, Watanabe T, Ozawa S, Furukawa H, Ishida H (1999) Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic beta-cells is involved in impaired insulin secretion from diabetic GK rat islets: restoration of decreased t-SNARE proteins improves impaired insulin secretion. Diabetes 48(12):2367–2373PubMedCrossRefGoogle Scholar
  31. Navarro M (2009) La suplementación con taurina modula la homeostasis de la glucosa y la función de los islotes pancreáticos. Universidad Pablo de Olavide Thesis Sevilla, España 2009Google Scholar
  32. Olofsson CS, Salehi A, Holm C, Rorsman P (2004) Palmitate increases L-type Ca2 + currents and the size of the readily releasable granule pool in mouse pancreatic beta-cells. J Physiol 557(Pt 3):935–948PubMedCentralPubMedCrossRefGoogle Scholar
  33. Park EJ, Bae JH, Kim SY, Lim JG, Baek WK, Kwon TK, Suh SI, Park JW, Lee IK, Ashcroft FM, Song DK (2004) Inhibition of ATP-sensitive K + channels by taurine through a benzamido-binding site on sulfonylurea receptor 1. Biochem Pharmacol 67(6):1089–1096PubMedCrossRefGoogle Scholar
  34. Peng Z, Xiaolei Z, Al-Sanaban H, Chengrui X, Shengyi Y (2012) Ghrelin inhibits insulin release by regulating the expression of inwardly rectifying potassium channel 6.2 in islets. Am J Med Sci 343(3):215–219PubMedCrossRefGoogle Scholar
  35. Reis MA, Carneiro EM, Mello MA, Boschero AC, Saad MJ, Velloso LA (1997) Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats. J Nutr 127(3):403–410PubMedGoogle Scholar
  36. Remacle C, Dumortier O, Bol V, Goosse K, Romanus P, Theys N, Bouckenooghe T, Reusens B (2007) Intrauterine programming of the endocrine pancreas. Diabetes Obes Metab 9(Suppl 2):196–209. doi: 10.1111/j.1463-1326.2007.00790.x PubMedCrossRefGoogle Scholar
  37. Ribeiro RA, Bonfleur ML, Amaral AG, Vanzela EC, Rocco SA, Boschero AC, Carneiro EM (2009) Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets. Diabetes Metab Res Rev 25(4):370–379PubMedCrossRefGoogle Scholar
  38. 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(8):1148–1155PubMedCrossRefGoogle Scholar
  39. 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(4):1791–1801PubMedCrossRefGoogle Scholar
  40. Rorsman P, Braun M, Zhang Q (2012) Regulation of calcium in pancreatic alpha- and beta-cells in health and disease. Cell Calcium 51(3–4):300–308PubMedCentralPubMedCrossRefGoogle Scholar
  41. Sandovici I, Smith NH, Nitert MD, Ackers-Johnson M, Uribe-Lewis S, Ito Y, Jones RH, Marquez VE, Cairns W, Tadayyon M, O’Neill LP, Murrell A, Ling C, Constancia M, Ozanne SE (2011) Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets. Proc Natl Acad Sci USA 108(13):5449–5454. doi: 10.1073/pnas.1019007108 PubMedCentralPubMedCrossRefGoogle Scholar
  42. Satoh H, Sperelakis N (1998) Review of some actions of taurine on ion channels of cardiac muscle cells and others. Gen Pharmacol 30(4):451–463PubMedCrossRefGoogle Scholar
  43. Smith AJ, Partridge CJ, Asipu A, Mair LA, Hunter M, Sivaprasadarao A (2006) Increased ATP-sensitive K + channel expression during acute glucose deprivation. Biochem Biophys Res Commun 348(3):1123–1131PubMedCrossRefGoogle Scholar
  44. Solon CS, Franci D, Ignacio-Souza LM, Romanatto T, Roman EA, Arruda AP, Morari J, Torsoni AS, Carneiro EM, Velloso LA (2012) Taurine enhances the anorexigenic effects of insulin in the hypothalamus of rats. Amino Acids 42(6):2403–2410. doi: 10.1007/s00726-011-1045-5 PubMedCrossRefGoogle Scholar
  45. Soriano S, Gonzalez A, Marroqui L, Tuduri E, Vieira E, Amaral AG, Batista TM, Rafacho A, Boschero AC, Nadal A, Carneiro EM, Quesada I (2010) Reduced insulin secretion in protein malnourished mice is associated with multiple changes in the beta-cell stimulus-secretion coupling. Endocrinology 151(8):3543–3554PubMedCrossRefGoogle Scholar
  46. Tokuyama Y, Fan Z, Furuta H, Makielski JC, Polonsky KS, Bell GI, Yano H (1996) Rat inwardly rectifying potassium channel Kir6.2: cloning electrophysiological characterization, and decreased expression in pancreatic islets of male Zucker diabetic fatty rats. Biochem Biophys Res Commun 220(3):532–538PubMedCrossRefGoogle Scholar
  47. Tricarico D, Barbieri M, Camerino DC (2000) Taurine blocks ATP-sensitive potassium channels of rat skeletal muscle fibres interfering with the sulphonylurea receptor. Br J Pharmacol 130(4):827–834PubMedCentralPubMedCrossRefGoogle Scholar
  48. Winzell MS, Magnusson C, Ahren B (2007) Temporal and dietary fat content-dependent islet adaptation to high-fat feeding-induced glucose intolerance in mice. Metabolism 56(1):122–128PubMedCrossRefGoogle Scholar
  49. Yang SN, Berggren PO (2006) The role of voltage-gated calcium channels in pancreatic beta-cell physiology and pathophysiology. Endocr Rev 27(6):621–676PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Jean F. Vettorazzi
    • 1
  • Rosane A. Ribeiro
    • 2
  • Junia C. Santos-Silva
    • 1
  • Patricia C. Borck
    • 1
  • Thiago M. Batista
    • 1
  • Tarlliza R. Nardelli
    • 1
  • Antonio C. Boschero
    • 1
  • Everardo M. Carneiro
    • 1
  1. 1.Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de BiologiaUniversidade Estadual de Campinas (UNICAMP)CampinasBrazil
  2. 2.NUPEM, Campus UFRJ-MacaéUniversidade Federal do Rio de JaneiroMacaéBrazil

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