Physical Exercise Introduced After Weaning Enhances Pancreatic Islet Responsiveness to Glucose and Potentiating Agents in Adult MSG-Obese Rats

Abstract

Physical exercise represents an alternative way to prevent and/or ameliorate chronic metabolic diseases. Disruption of sympathetic nervous system (SNS) activity contributes to adiposity in obese subjects. Here, we verified the preventive effect of swimming training upon adiposity, adrenal catecholamine storage, and pancreatic islet function in obese monosodium glutamate (MSG)-treated rats. Male neonatal Wistar rats received MSG (4 mg/g body weight) during the first 5 days of life and, at weaning, half of the rats were submitted to swimming training, 30 min/day, 3 days a week, until 90 days of age (exercised rats: MSGex). Half of the rats were used as controls (sedentary group, MSGsd). Exercise training (ET) decreased insulinemia and fat deposition in MSGex, and increased adrenal catecholamine content, compared with MSGsd rats. Insulinemia during the ivGTT was lower in MSGex rats, despite a lack of difference in glycemia. Swimming training enhanced insulin release in islets challenged by 2.8–8.3 mmol/l glucose, whereas, at supraphysiological glucose concentrations (11.1–16.7 mmol/l), MSGex islets secreted less insulin than MSGsd. No differences in insulin secretion were observed following l-arginine (Arg) or K⁺ stimuli. In contrast, islets from MSGex rats secreted more insulin when exposed to carbachol (100 μmol/l), forskolin (10 μmol/l), or IBMX (1 mmol/l) at 8.3 mmol/l glucose. Additionally, MSGex islets presented a better epinephrine inhibition upon insulin release. These results demonstrate that ET prevented the onset of obesity in MSG rats, probably by enhancing adrenal catecholamine levels. ET ameliorates islet responsiveness to several compounds, as well as insulin peripheral action.

Key words

adrenal catecholamine - exercise training - insulin secretion - MSG-obese rats - swimming training

• References

• 1 Arrone LJ, Mackintosh R, Rosenbaum M, Leibel RL, Hirsch J. Cardiac autonomic nervous system activity in obese and never-obese young men. Obes Res 1997; 5: 354-359
• 2 Kahn SE, Prigeon RL, Schwartz RS, Fujimoto WY, Knopp RH, Brunzell JD, Porte Jr D. Obesity, body fat distribution, insulin sensitivity and Islet beta-cell function as explanations for metabolic diversity. J Nutr 2001; 131: 354S-360S
• 3 Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 2003; 46: 3-19
• 4 Bray GA, York DA. Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol Rev 1979; 59: 719-809
• 5 Bray GA, York DA. The MONA LISA hypothesis in the time of leptin. Recent Prog Horm Res 1998; 53: 95-117 discussion 117–118
• 6 Scomparin DX, Gomes RM, Grassiolli S, Rinaldi W, Martins AG, de Oliveira JC, Gravena C, de Freitas Mathias PC. Autonomic activity and glycemic homeostasis are maintained by precocious and low intensity training exercises in MSG-programmed obese mice. Endocrine 2009; 36: 510-517
• 7 Atef N, Ktorza A, Picon L, Penicaud L. Increased islet blood flow in obese rats: role of the autonomic nervous system. Am J Physiol 1992; 262: E736-E740
• 8 Leigh FS, Kaufman LN, Young JB. Diminished epinephrine excretion in genetically obese (ob/ob) mice and monosodium glutamate-treated rats. Int J Obes Relat Metab Disord 1992; 16: 597-604
• 9 Weyer C, Salbe AD, Lindsay RS, Pratley RE, Bogardus C, Tataranni PA. Exaggerated pancreatic polypeptide secretion in Pima Indians: can an increased parasympathetic drive to the pancreas contribute to hyperinsulinemia, obesity, and diabetes in humans?. Metabolism 2001; 50: 223-230
• 10 Quilliot D, Zannad F, Ziegler O. Impaired response of cardiac autonomic nervous system to glucose load in severe obesity. Metabolism 2005; 54: 966-974
• 11 Inoue S, Bray GA. The effects of subdiaphragmatic vagotomy in rats with ventromedial hypothalamic obesity. Endocrinology 1977; 100: 108-114
• 12 Edvell A, Lindstrom P. Vagotomy in young obese hyperglycemic mice: effects on syndrome development and islet proliferation. Am J Physiol 1998; 274: E1034-E1039
• 13 Balbo SL, Mathias PC, Bonfleur ML, Alves HF, Siroti FJ, Monteiro OG, Ribeiro FB, Souza AC. Vagotomy reduces obesity in MSG-treated rats. Res Commun Mol Pathol Pharmacol 2000; 108: 291-296
• 14 Balbo SL, Grassiolli S, Ribeiro RA, Bonfleur ML, Gravena C, Brito Mdo N, Andreazzi AE, Mathias PC, Torrezan R. Fat storage is partially dependent on vagal activity and insulin secretion of hypothalamic obese rat. Endocrine 2007; 31: 142-148
• 15 Scheurink AJ, Steffens AB, Roossien B, Balkan B. Sympathoadrenal function in genetically obese Zucker rats. Physiol Behav 1992; 52: 679-685
• 16 Barnard RJ, Wen SJ. Exercise and diet in the prevention and control of the metabolic syndrome. Sports Med 1994; 18: 218-228
• 17 Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 1969; 164: 719-721
• 18 Olney JW. Glutamate-induced neuronal necrosis in the infant mouse hypothalamus. An electron microscopic study. J Neuropathol Exp Neurol 1971; 30: 75-90
• 19 Martins AC, Souza KL, Shio MT, Mathias PC, Lelkes PI, Garcia RM. Adrenal medullary function and expression of catecholamine-synthesizing enzymes in mice with hypothalamic obesity. Life Sci 2004; 74: 3211-3222
• 20 Nardelli TR, Ribeiro RA, Balbo SL, Vanzela EC, Carneiro EM, Boschero AC, Bonfleur ML. Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamate-obese rats. Amino Acids 2011; 41: 901-908
• 21 Ribeiro RA, Balbo SL, Roma LP, Camargo RL, Barella LF, Vanzela EC, Carneiro EM, Boschero AC, Bonfleur ML. Impaired muscarinic type 3 (M3) receptor/PKC and PKA pathways in islets form MSG-obese rats. Mol Biol Rep 2013; 40: 4521-4528
• 22 Scomparin DX, Grassiolli S, Marcal AC, Gravena C, Andreazzi AE, Mathias PC. Swim training applied at early age is critical to adrenal medulla catecholamine content and to attenuate monosodium L-glutamate-obesity onset in mice. Life Sci 2006; 79: 2151-2156
• 23 Andreazzi AE, Scomparin DX, Mesquita FP, Balbo SL, Gravena C, De Oliveira JC, Rinaldi W, Garcia RM, Grassiolli S, Mathias PC. Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium L-glutamate-obesity in mice. J Endocrinol 2009; 201: 351-359
• 24 Scomparin DX, Grassiolli S, Gomes RM, Torrezan R, de Oliveira JC, Gravena C, Pera CC, Mathias PC. Low-Intensity swimming training after weaning improves glucose and lipid homeostasis in MSG hypothalamic obese mice. Endocr Res 2011; 36: 83-90
• 25 Delghingaro-Augusto V, Decary S, Peyot ML, Latour MG, Lamontagne J, Paradis-Isler N, Lacharite-Lemieux M, Akakpo H, Birot O, Nolan CJ, Prentki M, Bergeron R. Voluntary running exercise prevents beta-cell failure in susceptible islets of the Zucker diabetic fatty rat. Am J Physiol Endocrinol Metab 2012; 302: E254-E264
• 26 Balbo SL, Bonfleur ML, Carneiro EM, Amaral ME, Filiputti E, Mathias PC. Parasympathetic activity changes insulin response to glucose and neurotransmitters. Diabetes Metab 2002; 28: 3S13-3S17 discussion 13S108–13S112
• 27 Harms PG, Ojeda SR. A rapid and simple procedure for chronic cannulation of the rat jugular vein. J Appl Physiol 1974; 36: 391-392
• 28 Ribeiro RA, Vanzela EC, Oliveira CA, Bonfleur ML, Boschero AC, Carneiro EM. 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 2010; 104: 1148-1155
• 29 Bernardis LL, Patterson BD. Correlation between ‛Lee index’ and carcass fat content in weanling and adult female rats with hypothalamic lesions. J Endocrinol 1968; 40: 527-528
• 30 Pollard HB, Ornberg R, Levine M, Brocklehurst K, Forsberg E, Lelkes PI, Morita K. Regulation of secretion from adrenal chromaffin cells. Physiologist 1985; 28: 247-254
• 31 Gautam D, Han SJ, Hamdan FF, Jeon J, Li B, Li JH, Cui Y, Mears D, Lu H, Deng C, Heard T, Wess J. A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo. Cell Metab 2006; 3: 449-461
• 32 Theintz GE. The endocrine impact of sports. Schweiz Med Wochenschr 1986; 116: 413-418
• 33 Nonogaki K. New insights into sympathetic regulation of glucose and fat metabolism. Diabetologia 2000; 43: 533-549
• 34 Holloszy JO. Exercise-induced increase in muscle insulin sensitivity. J Appl Physiol (1985) 2005; 99: 338-343
• 35 Frosig C, Richter EA. Improved insulin sensitivity after exercise: focus on insulin signaling. Obesity (Silver Spring) 2009; 17 (Suppl. 03) S15-S20
• 36 Corcoran MP, Lamon-Fava S, Fielding RA. Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise. Am J Clin Nutr 2007; 85: 662-677
• 37 Miranda RA, Branco RC, Gravena C, Barella LF, da Silva Franco CC, Andreazzi AE, de Oliveira JC, Picinato MC, de Freitas Mathias PC. Swim training of monosodium L-glutamate-obese mice improves the impaired insulin receptor tyrosine phosphorylation in pancreatic islets. Endocrine 2013; 43: 571-578
• 38 Zoppi CC, Calegari VC, Silveira LR, Carneiro EM, Boschero AC. Exercise training enhances rat pancreatic islets anaplerotic enzymes content despite reduced insulin secretion. Eur J Appl Physiol 2011; 111: 2369-2374
• 39 Calegari VC, Zoppi CC, Rezende LF, Silveira LR, Carneiro EM, Boschero AC. Endurance training activates AMP-activated protein kinase, increases expression of uncoupling protein 2 and reduces insulin secretion from rat pancreatic islets. J Endocrinol 2011; 208: 257-264
• 40 Tsuchiya M, Manabe Y, Yamada K, Furuichi Y, Hosaka M, Fujii NL. Chronic exercise enhances insulin secretion ability of pancreatic islets without change in insulin content in non-diabetic rats. Biochem Biophys Res Commun 2013; 430: 676-682
• 41 Wang YH, Hu H, Wang SP, Tian ZJ, Zhang QJ, Li QX, Li YY, Yu XJ, Sun L, Li DL, Jia B, Liu BH, Zang WJ. Exercise benefits cardiovascular health in hyperlipidemia rats correlating with changes of the cardiac vagus nerve. Eur J Appl Physiol 2010; 108: 459-468
• 42 Urano Y, Sakurai T, Ueda H, Ogasawara J, Sakurai T, Takei M, Izawa T. Desensitization of the inhibitory effect of norepinephrine on insulin secretion from pancreatic islets of exercise-trained rats. Metabolism 2004; 53: 1424-1432