Abstract
An imbalance of the autonomic nervous system (ANS) is suggested to be involved in insulin hypersecretion in obesity. Taurine (Tau) shows anti-obesity effects and regulates pancreatic islet function. Here, we evaluated obesity development and insulin secretion in response to cholinergic/protein kinase (PK)-C and PKA activation in ob/ob mice supplemented with Tau. From weaning until 90 days of age, male and female C57Bl/6 (C) and ob/ob mice (ob) were supplemented (CT and obT), or not, with 5 % Tau. Female and male ob mice presented higher body weight and fat stores. Tau did not alter adiposity in the obT groups. Islets isolated from female and male ob mice hypersecreted insulin in response to 5.6 and 11.1 mM glucose without or with 100 μM Cch (carbachol), 100 nM PMA (phorbol-12-myristate-13-acetate) or 10 μM forskolin. Additionally, Cch-induced higher intracellular Ca2+ mobilization in ob islets. Islets from the female ob group were not responsive to the inhibitory action of phenylephrine (Phe). Tau decreased insulin release at 5.6 mM glucose without or with PMA in obT. At 11.1 mM glucose, the female obT group presented normal insulin secretion at Cch, PMA and Phe, whereas male obT partially decreased secretion following PMA and forskolin stimuli. Ca2+ mobilization induced by Cch is partially reduced in female obT. Therefore, ob islets presented hypersecretion in glucose and potentiating agents. Despite not preventing the development of obesity, the normalization of the cholinergic/PKC pathway and the improvement in the action of Phe, indicate that Tau may regulate the ANS actions upon endocrine pancreas in obesity.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Abbreviations
- Ach:
-
Acetylcholine
- AUC:
-
Area under curve
- ANS:
-
Autonomic nervous system
- BW:
-
Body weight
- BSA:
-
Bovine serum albumin
- Cch:
-
Carbachol
- C:
-
Control
- cAMP:
-
Cyclic adenosine monophosphate
- CT:
-
CTL supplemented with Tau
- [Ca2+]i:
-
Intracellular Ca2+ concentration
- DAG:
-
Diacylglycerol
- DZX:
-
Diazoxide
- IP3:
-
Inositol 1,4,5-trisphosphate
- KRB:
-
Krebs–Ringer bicarbonate
- M3:
-
Muscarinic type 3 receptor
- ob:
-
Leptin-deficient obese mice
- obT:
-
ob supplemented with Tau
- Phe:
-
Phenylephrine
- PMA:
-
Phorbol-12-myristate-13-acetate
- PK:
-
Protein kinase
- PL:
-
Phospholipase
- PNS:
-
Parasympathetic nervous system
- RIA:
-
Radioimmunoassay
- SNS:
-
Sympathetic nervous system
- Tau:
-
Taurine
- T2D:
-
Type 2 diabetes
References
Ahren B (2000) Autonomic regulation of islet hormone secretion–implications for health and disease. Diabetologia 43:393
Ahren B (2008) Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans. Diabetologia 51:1018
Balbo SL, Grassiolli S, Ribeiro RA, Bonfleur ML, Gravena C, Brito Mdo N, Andreazzi AE, Mathias PC, Torrezan R (2007) Fat storage is partially dependent on vagal activity and insulin secretion of hypothalamic obese rat. Endocrine 31:142
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 23:306
Bernardis LL, Patterson BD (1968) Correlation between ‘Lee index’ and carcass fat content in weanling and adult female rats with hypothalamic lesions. J Endocrinol 40:527
Black M, Heick HM, Begin-Heick N (1986) Abnormal regulation of insulin secretion in the genetically obese (ob/ob) mouse. Biochem J 238:863
Black MA, Fournier LA, Heick HM, Begin-Heick N (1988) Different insulin-secretory responses to calcium-channel blockers in islets of lean and obese (ob/ob) mice. Biochem J 249:401
Boschero AC, Szpak-Glasman M, Carneiro EM, Bordin S, Paul I, Rojas E, Atwater I (1995) Oxotremorine-m potentiation of glucose-induced insulin release from rat islets involves M3 muscarinic receptors. Am J Physiol 268:E336
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 20:503
Cerf ME (2013) Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne) 4:37
Chen H, Li J, Liu J, Liu L, Liu N, Song YZ (2009) Effects of prenatal taurine on mRNA expression of PKA CREB signal pathway and glial cell line derived neurotrophic factor in fetal rat brains of intrauterine growth restriction. Zhongguo Dang Dai Er Ke Za Zhi 11:923–926
Chen NG, Romsos DR (1997) Persistently enhanced sensitivity of pancreatic islets from ob/ob mice to PKC-stimulated insulin secretion. Am J Physiol 272:E304
Chen NG, Tassava TM, Romsos DR (1993) Threshold for glucose-stimulated insulin secretion in pancreatic islets of genetically obese (ob/ob) mice is abnormally low. J Nutr 123:1567
Cruciani-Guglielmacci C, Vincent-Lamon M, Rouch C, Orosco M, Ktorza A, Magnan C (2005) Early changes in insulin secretion and action induced by high-fat diet are related to a decreased sympathetic tone. Am J Physiol Endocrinol Metab 288:E148
Das J, Ghosh J, Manna P, Sil PC (2010) Protective role of taurine against arsenic-induced mitochondria-dependent hepatic apoptosis via the inhibition of PKCdelta-JNK pathway. PLoS One 5:e12602
Dolz M, Bailbe D, Giroix MH, Calderari S, Gangnerau MN, Serradas P, Rickenbach K, Irminger JC, Portha B (2005) Restitution of defective glucose-stimulated insulin secretion in diabetic GK rat by acetylcholine uncovers paradoxical stimulatory effect of beta-cell muscarinic receptor activation on cAMP production. Diabetes 54:3229
Dyachok O, Idevall-Hagren O, Sagetorp J, Tian G, Wuttke A, Arrieumerlou C, Akusjarvi G, Gylfe E, Tengholm A (2008) Glucose-induced cyclic AMP oscillations regulate pulsatile insulin secretion. Cell Metab 8:26
Edvell A, Lindstrom P (1998) Vagotomy in young obese hyperglycemic mice: effects on syndrome development and islet proliferation. Am J Physiol 274:E1034
Freitag A, Wessler I, Racke K (1998) Phosphodiesterase inhibitors suppress alpha2-adrenoceptor-mediated 5-hydroxytryptamine release from tracheae of newborn rabbits. Eur J Pharmacol 354:67
Fujita T, Sato Y (1988) Hypotensive effect of taurine Possible involvement of the sympathetic nervous system and endogenous opiates. J Clin Invest 82:993
Gilon P, Henquin JC (2001) Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function. Endocr Rev 22:565
Hano T, Kasano M, Tomari H, Iwane N (2009) Taurine suppresses pressor response through the inhibition of sympathetic nerve activity and the improvement in baro-reflex sensitivity of spontaneously hypertensive rats. Adv Exp Med Biol 643:57
Hillaire-Buys D, Gross R, Blayac JP, Ribes G, Loubatieres-Mariani MM (1985) Effects of alpha-adrenoceptor agonists and antagonists on insulin secreting cells and pancreatic blood vessels: comparative study. Eur J Pharmacol 117:253
Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72:101
Ito T, Pastukh V, Solodushko V, Azuma J, Schaffer SW (2009) Effect of taurine on protein kinase C isoforms: role in taurine’s actions? Adv Exp Med Biol 643:3
Joseph SK, Ryan SV (1993) Phosphorylation of the inositol trisphosphate receptor in isolated rat hepatocytes. J Biol Chem 268:23059
Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840
Lee HC, Curry DL, Stern JS (1989) Direct effect of CNS on insulin hypersecretion in obese Zucker rats: involvement of vagus nerve. Am J Physiol 256:E439
Lee HC, Curry DL, Stern JS (1993) Tonic sympathetic nervous system inhibition of insulin secretion is diminished in obese Zucker rats. Obes Res 1:371
Lehmann A, Hamberger A (1984) Inhibition of cholinergic response by taurine in frog isolated skeletal muscle. J Pharm Pharmacol 36:59
Lindstrom P (2010) Beta-cell function in obese-hyperglycemic mice [ob/ob Mice]. Adv Exp Med Biol 654:463
Liu J, Liu Y, Wang XF, Chen H, Yang N (2013) Antenatal taurine supplementation improves cerebral neurogenesis in fetal rats with intrauterine growth restriction through the PKA-CREB signal pathway. Nutr Neurosci 16:282
Magnan C, Cruciani C, Clement L, Adnot P, Vincent M, Kergoat M, Girard A, Elghozi JL, Velho G, Beressi N, Bresson JL, Ktorza A (2001) Glucose-induced insulin hypersecretion in lipid-infused healthy subjects is associated with a decrease in plasma norepinephrine concentration and urinary excretion. J Clin Endocrinol Metab 86:4901
Mizushima S, Nara Y, Sawamura M, Yamori Y (1996) Effects of oral taurine supplementation on lipids and sympathetic nerve tone. Adv Exp Med Biol 403:615
Pina-Zentella G, de la Rosa-Cuevas G, Vazquez-Meza H, Pina E, de Pina MZ (2012) Taurine in adipocytes prevents insulin-mediated H2O2 generation and activates Pka and lipolysis. Amino Acids 42:1927
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 25:370
Ribeiro RA, Bonfleur ML, Vanzela EC, Zotti AI, Scomparin DX, Boschero AC, Balbo SL (2014) Physical Exercise Introduced After Weaning Enhances Pancreatic Islet Responsiveness to Glucose and Potentiating Agents in Adult MSG-Obese Rats. Horm Metab Res 46(9):609–614
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
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
Sato Y, Ogata E, Fujita T (1991) Hypotensive action of taurine in DOCA-salt rats–involvement of sympathoadrenal inhibition and endogenous opiate. Jpn Circ J 55:500
Scomparin DX, Gomes RM, Grassiolli S, Rinaldi W, Martins AG, de Oliveira JC, Gravena C, de Freitas Mathias PC (2009) Autonomic activity and glycemic homeostasis are maintained by precocious and low intensity training exercises in MSG-programmed obese mice. Endocrine 36:510
Shikora S, Toouli J, Herrera MF, Kulseng B, Zulewski H, Brancatisano R, Kow L, Pantoja JP, Johnsen G, Brancatisano A, Tweden KS, Knudson MB, Billington CJ (2013) Vagal blocking improves glycemic control and elevated blood pressure in obese subjects with type 2 diabetes mellitus. J Obes 2013:245683
Singewald N, Kouvelas D, Chen F, Philippu A (1997) The release of inhibitory amino acids in the hypothalamus is tonically modified by impulses from aortic baroreceptors as a consequence of blood pressure fluctuations. Naunyn Schmiedebergs Arch Pharmacol 356:348
Tassava TM, Okuda T, Romsos DR (1992) Insulin secretion from ob/ob mouse pancreatic islets: effects of neurotransmitters. Am J Physiol 262:E338
Tomita T, Doull V, Pollock HG, Krizsan D (1992) Pancreatic islets of obese hyperglycemic mice (ob/ob). Pancreas 7:367
Wang YC, Guan FY, Li H, Yang SJ (2009) Anti-proliferation action of taurine on rat cardiac fibroblast through inhibiting protein kinase Calpha expression. Yao Xue Xue Bao 44:591
Yoshimatsu H, Niijima A, Oomura Y, Yamabe K, Katafuchi T (1984) Effects of hypothalamic lesion on pancreatic autonomic nerve activity in the rat. Brain Res 303:147
Yoshimura R, Omori H, Somekawa S, Osaka T, Ito R, Inoue S, Endo Y (2006) Continuous carbachol infusion promotes peripheral cell proliferation and mimics vagus hyperactivity in a rat model of hypothalamic obesity. Biomed Res 27:81
Acknowledgements
This study is part of a PhD Thesis (JC Santos-Silva) and was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2009/54153-7) and Instituto Nacional de Obesidade e Diabetes (CNPq/FAPESP). Authors thank Marise Carnelossi for excellent technical assistance and Nicola Conran for editing the English.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this paper
Cite this paper
Santos-Silva, J.C., Ribeiro, R.A., Vettorazzi, J.F., Borck, P.C., Boschero, A.C., Carneiro, E.M. (2015). Taurine Supplementation Regulates Pancreatic Islet Function in Response to Potentiating Agents in Leptin-Deficient Obese Mice. In: Marcinkiewicz, J., Schaffer, S. (eds) Taurine 9. Advances in Experimental Medicine and Biology, vol 803. Springer, Cham. https://doi.org/10.1007/978-3-319-15126-7_28
Download citation
DOI: https://doi.org/10.1007/978-3-319-15126-7_28
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-15125-0
Online ISBN: 978-3-319-15126-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)