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Impaired β-cell function in the adult offspring of rats fed a protein-restricted diet during lactation is associated with changes in muscarinic acetylcholine receptor subtypes

  • Júlio C. de Oliveira (a1), Rosiane A. Miranda (a1), Luiz F. Barella (a1), Rosana Torrezan (a2), Aryane R. Agostinho (a1), Tatiane A. S. Ribeiro (a1), Claudinéia C. S. Franco (a1), Ananda Malta (a1), Laize P. Tófolo (a1), Clarice Gravena (a1) and Paulo C. F. Mathias (a1)...

Abstract

Impaired pancreatic β-cell function, as observed in the cases of early nutrition disturbance, is a major hallmark of metabolic diseases arising in adulthood. In the present study, we aimed to investigate the function/composition of the muscarinic acetylcholine receptor (mAChR) subtypes, M2 and M3, in the pancreatic islets of adult offspring of rats that were protein malnourished during lactation. Neonates were nursed by mothers that were fed either a low-protein (4 %, LP) or a normal-protein (23 %, NP) diet. Adult rats were pre-treated with anti-muscarinic drugs and subjected to the glucose tolerance test; the function and protein expression levels of M2mAChR and M3mAChR were determined. The LP rats were lean and hypoinsulinaemic. The selective M2mAChR antagonist methoctramine increased insulinaemia by 31 % in the NP rats and 155 % in the LP rats, and insulin secretion was increased by 32 % in the islets of the NP rats and 88 % in those of the LP rats. The selective M3mAChR antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide decreased insulinaemia by 63 % in the NP rats and 40 % in the LP rats and reduced insulin release by 41 % in the islets of the NP rats and 28 % in those of the LP rats. The protein expression levels of M2mAChR and M3mAChR were 57 % higher and 53 % lower, respectively, in the islets of the LP rats than in those of the NP rats. The expression and functional compositions of M2mAChR and M3mAChR were altered in the islets of the LP rats, as a result of metabolic programming caused by the protein-restricted diet, which might be another possible effect involved in the weak insulin secretion ability of the islets of the programmed adult rats.

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Corresponding author

* Corresponding author: P. C. F. Mathias, fax +55 44 3011 4892, email pmathias@uem.br

References

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1 Markakis, EA (2002) Development of the neuroendocrine hypothalamus. Front Neuroendocrinol 23, 257291.
2 Heijmans, BT, Tobi, EW, Stein, AD, et al. (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105, 17046–11749.
3 Sinclair, KD, Allegrucci, C, Singh, R, et al. (2007) DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A 104, 1935119356.
4 McMullen, S & Mostyn, A (2009) Animal models for the study of the developmental origins of health and disease. Proc Nutr Soc 68, 306320.
5 Hales, CN & Barker, DJ (2001) The thrifty phenotype hypothesis. Br Med Bull 60, 520.
6 Barker, DJ (2004) The developmental origins of chronic adult disease. Acta Paediatr Suppl 93, 2633.
7 Reusens, B & Remacle, C (2006) Programming of the endocrine pancreas by the early nutritional environment. Int J Biochem Cell Biol 38, 913922.
8 Holness, MJ, Langdown, ML & Sugden, MC (2000) Early-life programming of susceptibility to dysregulation of glucose metabolism and the development of type 2 diabetes mellitus. Biochem J 349, 657665.
9 Barbosa, FB, Capito, K, Kofod, H, et al. (2002) Pancreatic islet insulin secretion and metabolism in adult rats malnourished during neonatal life. Br J Nutr 87, 147155.
10 James, WP & Coore, HG (1970) Persistent impairment of insulin secretion and glucose tolerance after malnutrition. Am J Clin Nutr 23, 386389.
11 Martin-Gronert, MS & Ozanne, SE (2006) Maternal nutrition during pregnancy and health of the offspring. Biochem Soc Trans 34, 779782.
12 Zambrano, E, Bautista, CJ, Deas, M, et al. (2006) A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat. J Physiol 571, 221230.
13 Fernandez-Twinn, DS, Wayman, A, Ekizoglou, S, et al. (2005) Maternal protein restriction leads to hyperinsulinemia and reduced insulin-signaling protein expression in 21-mo-old female rat offspring. Am J Physiol Regul Integr Comp Physiol 288, R368R373.
14 de Souza Caldeira Filho, J & Moura, AS (2000) Undernutrition during early lactation period induces metabolic imprinting leading to glucose homeostasis alteration in aged rats. Res Commun Mol Pathol Pharmacol 108, 213226.
15 Morimoto, S, Calzada, L, Sosa, TC, et al. (2011) Emergence of ageing-related changes in insulin secretion by pancreatic islets of male rat offspring of mothers fed a low-protein diet. Br J Nutr 9, 14.
16 Ahren, B (2000) Autonomic regulation of islet hormone secretion – implications for health and disease. Diabetologia 43, 393410.
17 Gilon, P & Henquin, JC (2001) Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function. Endocr Rev 22, 565604.
18 de Oliveira, JC, Scomparin, DX, Andreazzi, AE, et al. (2011) Metabolic imprinting by maternal protein malnourishment impairs vagal activity in adult rats. J Neuroendocrinol 23, 148157.
19 Gravena, C, Andreazzi, AE, Mecabo, FT, et al. (2007) Protein restriction during lactation alters the autonomic nervous system control on glucose-induced insulin secretion in adult rats. Nutr Neurosci 10, 7987.
20 Leon-Quinto, T, Magnan, C & Portha, B (1998) Altered activity of the autonomous nervous system as a determinant of the impaired beta-cell secretory response after protein-energy restriction in the rat. Endocrinology 139, 33823389.
21 Renuka, TR, Robinson, R & Paulose, CS (2006) Increased insulin secretion by muscarinic M1 and M3 receptor function from rat pancreatic islets in vitro . Neurochem Res 31, 313320.
22 Winzell, MS & Ahren, B (2007) G-protein-coupled receptors and islet function-implications for treatment of type 2 diabetes. Pharmacol Ther 116, 437448.
23 Drucker, DJ (2006) The biology of incretin hormones. Cell Metabolism 3, 153165.
24 Gautam, D, Duttaroy, A, Cui, Y, et al. (2006) M1–M3 muscarinic acetylcholine receptor-deficient mice: novel phenotypes. J Mol Neurosci 30, 157160.
25 Lopes Da Costa, C, Sampaio De Freitas, M & Sanchez Moura, A (2004) Insulin secretion and GLUT-2 expression in undernourished neonate rats. J Nutr Biochem 15, 236241.
26 Barbosa, FB, Medina, AR, Balbo, SL, et al. (1999) Low protein diets administered to lactating rats affect in a time-dependent manner the development of young. Res Commun Mol Pathol Pharmacol 106, 6376.
27 Trinder, P (1969) Determination of blood glucose using an oxidase–peroxidase system with a non-carcinogenic chromogen. J Clin Pathol 22, 158161.
28 Scott, AM, Atwater, I & Rojas, E (1981) A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans. Diabetologia 21, 470475.
29 Gravena, C, Mathias, PC & Ashcroft, SJ (2002) Acute effects of fatty acids on insulin secretion from rat and human islets of Langerhans. J Endocrinol 173, 7380.
30 Laemmli, UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680685.
31 Iismaa, TP, Kerr, EA, Wilson, JR, et al. (2000) Quantitative and functional characterization of muscarinic receptor subtypes in insulin-secreting cell lines and rat pancreatic islets. Diabetes 49, 392398.
32 Ozanne, SE, Wang, CL, Coleman, N, et al. (1996) Altered muscle insulin sensitivity in the male offspring of protein-malnourished rats. Am J Physiol 271, E1128E1134.
33 Garcia-Souza, EP, Da Silva, SV, Felix, GB, et al. (2008) Maternal protein restriction during early lactation induces GLUT4 translocation and mTOR/AKT activation in adipocytes of adults rats. Am J Physiol Endocrinol Metab 295, E626E636.
34 Latorraca, MQ, Reis, MA, Carneiro, EM, et al. (1998) Protein deficiency and nutritional recovery modulate insulin secretion and the early steps of insulin action in rats. J Nutr 128, 16431649.
35 Dong, XY & Tang, SQ (2010) Insulin-induced gene: a new regulator in lipid metabolism. Peptides 31, 21452150.
36 Rodriguez-Trejo, A, Ortiz-Lopez, MG, Zambrano, E, et al. (2012) Developmental programming of neonatal pancreatic beta-cells by a maternal low-protein diet in rats involves a switch from proliferation to differentiation. Am J Physiol Endocrinol Metab 302, E1431E1439.
37 Gautam, D, Han, SJ, Hamdan, FF, et al. (2006) A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo . Cell Metab 3, 449461.
38 Gautam, D, Ruiz de Azua, I, Li, JH, et al. (2010) Beneficial metabolic effects caused by persistent activation of beta-cell M3 muscarinic acetylcholine receptors in transgenic mice. Endocrinology 151, 51855194.
39 Yamada, M, Miyakawa, T, Duttaroy, A, et al. (2001) Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature 410, 207212.
40 Gautam, D, Gavrilova, O, Jeon, J, et al. (2006) Beneficial metabolic effects of M3 muscarinic acetylcholine receptor deficiency. Cell Metab 4, 363375.
41 Wells, JC (2007) The thrifty phenotype as an adaptive maternal effect. Biol Rev Camb Philos Soc 82, 143172.
42 Huang, JS, Lee, TA & Lu, MC (2007) Prenatal programming of childhood overweight and obesity. Matern Child Health J 11, 461473.
43 Ravelli, AC, van Der Meulen, JH, Osmond, C, et al. (1999) Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr 70, 811816.
44 Erhuma, A, Bellinger, L, Langley-Evans, SC, et al. (2007) Prenatal exposure to undernutrition and programming of responses to high-fat feeding in the rat. Br J Nutr 98, 517524.
45 Orozco-Solis, R, Lopes de Souza, S, Barbosa Matos, RJ, et al. (2009) Perinatal undernutrition-induced obesity is independent of the developmental programming of feeding. Physiol Behav 96, 481492.
46 Vickers, MH, Gluckman, PD, Coveny, AH, et al. (2005) Neonatal leptin treatment reverses developmental programming. Endocrinology 146, 42114216.
47 Ozanne, SE & Hales, CN (2004) Lifespan: catch-up growth and obesity in male mice. Nature 427, 411412.
48 Ruiz de Azua, I, Gautam, D, Guettier, JM, et al. (2011) Novel insights into the function of beta-cell M3 muscarinic acetylcholine receptors: therapeutic implications. Trends Endocrinol Metab 22, 7480.
49 Passos, MCF, Ramos, CF & Moura, EG (2000) Short and long term effects of malnutrition in rats during lactation on the body weight of offspring. Nutr Res 20, 16031612.
50 Bautista, CJ, Boeck, L, Larrea, F, et al. (2008) Effects of a maternal low protein isocaloric diet on milk leptin and progeny serum leptin concentration and appetitive behavior in the first 21 days of neonatal life in the rat. Pediatr Res 63, 358363.
51 Bouret, SG & Simerly, RB (2004) Minireview: leptin and development of hypothalamic feeding circuits. Endocrinology 145, 26212626.
52 Arantes, VC, Teixeira, VP, Reis, MA, et al. (2002) Expression of PDX-1 is reduced in pancreatic islets from pups of rat dams fed a low protein diet during gestation and lactation. J Nutr 132, 30303035.

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