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Protein malnutrition early in life increased apoptosis but did not alter the β-cell mass during gestation

Published online by Cambridge University Press:  11 September 2020

Daniela de Souza Vial-Dahmer
Affiliation:
Mestrado em Biociências, Faculdade de Nutrição, Universidade Federal de Mato Grosso, Cuiabá, MT, 78060-900, Brazil
Chaiane Aline da Rosa-Santos
Affiliation:
Mestrado em Nutrição, Alimentos e Metabolismo, Faculdade de Nutrição, Universidade Federal de Mato Grosso, Cuiabá, MT, 78060-900, Brazil
Luana Resende Silva
Affiliation:
Mestrado em Nutrição, Alimentos e Metabolismo, Faculdade de Nutrição, Universidade Federal de Mato Grosso, Cuiabá, MT, 78060-900, Brazil
Vanessa Cristina Arantes
Affiliation:
Departamento de Alimentos e Nutrição, Faculdade de Nutrição, Universidade Federal de Mato Grosso, Cuiabá, MT, 78060-900, Brazil
Marise Auxiliadora de Barros Reis
Affiliation:
Departamento de Alimentos e Nutrição, Faculdade de Nutrição, Universidade Federal de Mato Grosso, Cuiabá, MT, 78060-900, Brazil
Marciane Milanski
Affiliation:
Laboratório de Distúrbios do Metabolismo, Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, SP, 13484-350, Brazil
Egberto Gaspar de Moura
Affiliation:
Departamento de Ciências Fisiológicas, Laboratório de Fisiologia Endócrina, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, 20551-031, Brazil
Patrícia Cristina Lisboa
Affiliation:
Departamento de Ciências Fisiológicas, Laboratório de Fisiologia Endócrina, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, 20551-031, Brazil
Everardo Magalhães Carneiro
Affiliation:
Departamento de Anatomia, Biologia Celular, Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, 13083-862, Brazil
Amílcar Sabino Damazo
Affiliation:
Departamento de Ciências Básicas da Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso, Cuiabá, MT, 78060-900, Brazil
Márcia Queiroz Latorraca
Affiliation:
Departamento de Alimentos e Nutrição, Faculdade de Nutrição, Universidade Federal de Mato Grosso, Cuiabá, MT, 78060-900, Brazil
Corresponding
E-mail address:

Abstract

We evaluated whether early-life protein restriction alters structural parameters that affect β-cell mass on the 15th day and 20th day of gestation in control pregnant (CP), control non-pregnant (CNP), low-protein pregnant (LPP) and low-protein non-pregnant (LPNP) rats from the fetal to the adult life stage as well as in protein-restricted rats that recovered after weaning (recovered pregnant (RP) and recovered non-pregnant). On the 15th day of gestation, the CNP group had a higher proportion of smaller islets, whereas the CP group exhibited a higher proportion of islets larger than the median. The β-cell mass was lower in the low-protein group than that in the recovered and control groups. Gestation increased the β-cell mass, β-cell proliferation frequency and neogenesis frequency independently of the nutritional status. The apoptosis frequency was increased in the recovered groups compared with that in the other groups. On the 20th day of gestation, a higher proportion of islets smaller than the median was observed in the non-pregnant groups, whereas a higher proportion of islets larger than the median was observed in the RP, LPP and CP groups. β-Cell mass was lower in the low-protein group than that in the recovered and control groups, regardless of the physiological status. The β-cell proliferation frequency was lower, whereas the apoptosis rate was higher in recovered rats compared with those in the low-protein and control rats. Thus, protein malnutrition early in life did not alter the mass of β-cells, especially in the first two-thirds of gestation, despite the increase in apoptosis.

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© The Author(s), 2020. Published by Cambridge University Press on behalf of The Nutrition Society

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References

Genevay, M, Pontes, H & Meda, P (2010) Beta cell adaptation in pregnancy: a major difference between humans and rodents? Diabetologia 53, 20892092.CrossRefGoogle Scholar
Fujimoto, K & Polonsky, KS (2009) Pdx1 and other factors that regulate pancreatic beta-cell survival. Diabetes Obes Metab 11, S30S37.CrossRefGoogle ScholarPubMed
Bonner-Weir, S (2001) Beta-cell turnover: its assessment and implications. Diabetes 50, S20S24.CrossRefGoogle ScholarPubMed
Teta, M, Long, SY, Wartschow, LM, et al. (2005) Very slow turnover of beta-cells in aged adult mice. Diabetes 54, 25572567.CrossRefGoogle ScholarPubMed
Pearl, S, Kushner, JA, Buchholz, BA, et al. (2010) Significant human β-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating. J Clin Endocrinol Metab 95, E234E239.CrossRefGoogle Scholar
Finegood, DT, Scaglia, L & Bonner-Weir, S (1995) Dynamics of β-cell mass in the growing rat pancreas: estimation with a simple mathematical model (Perspective). Diabetes 44, 249256.CrossRefGoogle Scholar
Thorel, F & Herrera, PL (2010) Conversion of adult pancreatic α-cells to b β-cells in diabetic mice. Med Sci 26, 906909.Google Scholar
Butler, PC, Meier, JJ, Butler, AE, et al. (2007) The replication of β cells in normal physiology, in disease and for therapy. Nat Clin Pract Endocrinol Metab 3, 758768.CrossRefGoogle ScholarPubMed
Parsons, JA, Brelje, TC & Sorenson, RL (1992) Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology 130, 14591466.Google ScholarPubMed
Van Assche, FA, Aerts, L & De Prins, F (1978) A morphological study of the endocrine pancreas in human pregnancy. Br J Obstet Gynaecol 85, 818820.CrossRefGoogle ScholarPubMed
Butler, AE, Cao-Minh, L, Galasso, R, et al. (2010) Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy. Diabetologia 53, 21672176.CrossRefGoogle ScholarPubMed
Rieck, S & Kaestner, KH (2010) Expansion of β-cell mass in response to pregnancy. Trends Endocrinol Metab 21, 151158.CrossRefGoogle Scholar
Berney, DM, Desai, M, Palmer, DJ, et al. (1997) The effects of maternal protein deprivation on the fetal rat pancreas: major structural changes and their recuperation. J Pathol 183, 109115.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
Petrik, J, Reusens, B, Arany, E, et al. (1999) A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II. Endocrinology 140, 48614873.CrossRefGoogle ScholarPubMed
Milanski, M, Arantes, VC, Ferreira, F, et al. (2005) Low-protein diets reduce PKAα expression in islets from pregnant rats. J Nutr 135, 18731878.CrossRefGoogle ScholarPubMed
Sorenson, RL & Brelje, TC (1997) Adaptation of islets of Langerhans to pregnancy: β-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm Metab Res 29, 301307.CrossRefGoogle ScholarPubMed
Kawai, M & Kishi, K (1999) Adaptation of pancreatic islet β-cells during the last third of pregnancy: regulation of β-cell function and proliferation by lactogenic hormones in rats. Eur J Endocrinol 141, 419425.CrossRefGoogle Scholar
Scott, AM, Atwater, I & Rojas, E (1981) A method for the simultaneous measurement of insulin released and β-cell membrane potential in single mouse islets of Langerhans. Diabetologia 21, 470475.CrossRefGoogle Scholar
Matsuda, M & DeFronzo, RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22, 14621470.CrossRefGoogle ScholarPubMed
Boschero, AC, Szpak-Glasman, N, Carneiro, EM, et al. (1995) Oxotremorine-m potentiation of glucose-induced insulin release from rat islets involves M3 muscarinic receptors. Am J Physiol 268, E336E342.Google ScholarPubMed
Scaglia, L, Cahill, CJ, Finegood, DT, et al. (1997) Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat. Endocrinology 138, 17361741.CrossRefGoogle ScholarPubMed
Charan, J & Kantharia, ND (2013) How to calculate sample size in animal studies? J Pharmacol Pharmacother 4, 303306.CrossRefGoogle ScholarPubMed
Sokal, RR & Rohlf, FJ (1995) Biometry: The Principles and Practice of Statistics in Biological Research, 3rd ed. New York, NY: W.H. Freeman and Company.Google Scholar
Lifson, N, Lassa, CV & Dixit, PK (1985) Relation between blood flow and morphology in islet organ of rat pancreas. Am J Physiol 249, E43E48.Google ScholarPubMed
Hellman, B (1959) The numerical distribution of the islets of Langerhans at different ages of the rat. Acta Endocrinol 32, 6377.CrossRefGoogle ScholarPubMed
Reaven, EP, Gold, G & Walker, W (1981) Effect of variations in islet size and shape on glucose-stimulated insulin secretion. Horm Metab Res 13, 673674.CrossRefGoogle ScholarPubMed
Ignácio-Souza, LM, Reis, SR, Arantes, VC, et al. (2013) Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy. Br J Nutr 109, 236247.CrossRefGoogle ScholarPubMed
Skau, M, Pakkenberg, B, Buschard, K, et al. (2001) Linear correlation between the total islet mass and the volume-weighted mean islet volume. Diabetes 50, 17631770.CrossRefGoogle ScholarPubMed
Nielsen, JH (2016) Beta cell adaptation in pregnancy: a tribute to Claes Hellerström. Ups J Med Sci 121, 151154.CrossRefGoogle ScholarPubMed
Montanya, E, Nacher, V, Biarnés, M, et al. (2000) Linear correlation between β-cell mass and body weight throughout the lifespan in Lewis rats: role of β-cell hyperplasia and hypertrophy. Diabetes 49, 13411346.CrossRefGoogle ScholarPubMed
Bonner-Weir, S, Deery, D, Leahy, JL, et al. (1989) Compensatory growth of pancreatic β-cells in adult rats after short-term glucose infusion. Diabetes 38, 4953.CrossRefGoogle ScholarPubMed
Chen, L, Appel, MC, Alam, T, et al. (1992) Factors regulating islet regeneration in the post-insulinoma NEDH rat. Adv Exp Med Biol 321, 7180.CrossRefGoogle ScholarPubMed
Jonas, JC, Sharma, A, Hasenkamp, W, et al. (1999) Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes. J Biol Chem 274, 1411214121.CrossRefGoogle Scholar
Swenne, I (1982) The role of glucose in the in vitro regulation of cell cycle kinetics and proliferation of fetal pancreatic β-cells. Diabetes 31, 754760.CrossRefGoogle Scholar
Alonso, LC, Yokoe, T, Zhang, P, et al. (2007) Glucose infusion in mice: a new model to induce β-cell replication. Diabetes 56, 17921801.CrossRefGoogle ScholarPubMed
Kilimnik, G, Kim, A, Steiner, DF, et al. (2010) Intraislet production of GLP-1 by activation of prohormone convertase 1/3 in pancreatic α-cells in mouse models of β-cell regeneration. Islets 2, 149155.CrossRefGoogle Scholar
Abouna, S, Old, RW, Pelengaris, S, et al. (2010) Non-β-cell progenitors of β-cells in pregnant mice. Organogenesis 6, 125133.CrossRefGoogle ScholarPubMed
Gao, T, McKenna, B, Li, C, et al. (2014) Pdx1 maintains β cell identity and function by repressing an α cell program. Cell Metab 19, 259271.CrossRefGoogle ScholarPubMed
Yang, YP, Thorel, F, Boyer, DF, et al. (2011) Context-specific-to-β-cell reprogramming by forced Pdx1 expression. Genes Dev 25, 16801685.CrossRefGoogle ScholarPubMed
Taniguchi, H, Yamato, E, Tashiro, F, et al. (2003) Beta-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas. Gene Ther 10, 1523.CrossRefGoogle ScholarPubMed
Hayes, HL, Moss, LG, Schisler, JC, et al. (2013) Pdx-1 activates islet – and β-cell proliferation via a mechanism regulated by transient receptor potential cation channels 3 and 6 and extracellular signal-regulated kinases 1 and 2. Mol Cell Biol 33, 40174029.CrossRefGoogle Scholar
Merezak, S, Hardikar, AA, Yajnik, CS, et al. (2001) Intrauterine low protein diet increases fetal β-cell sensitivity to NO and IL-1 β: the protective role of taurine. J Endocrinol 171, 299308.CrossRefGoogle ScholarPubMed
Merezak, S, Reusens, B, Renard, A, et al. (2004) Effect of maternal low-protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines. Diabetologia 47, 669675.Google ScholarPubMed
Goosse, K, Balteau, M, Reusens, B, et al. (2009) Implication of nitric oxide in the increased islet-cells vulnerability of adult progeny from protein-restricted mothers and its prevention by taurine. J Endocrinol 200, 177187.CrossRefGoogle ScholarPubMed
Smaili, S, Hirata, H, Ureshino, R, et al. (2009) Calcium and cell death signaling in neurodegeneration and aging. An Acad Bras Cienc 81, 467475.CrossRefGoogle ScholarPubMed
Nicotera, P & Rossi, AD (1994) Nuclear Ca2+: physiological regulation and role in apoptosis. Mol Cell Biochem 135, 8998.CrossRefGoogle ScholarPubMed
Marin, BK, de Lima Reis, SR, de Fátima Silva Ramalho, A, et al. (2019) Protein restriction in early life increases intracellular calcium and insulin secretion, but does not alter expression of SNARE proteins during pregnancy. Exp Physiol 104, 10291037.CrossRefGoogle Scholar
Tomita, T (2016) Apoptosis in pancreatic β-islet cells in type 2 diabetes. Bosn J Basic Med Sci 16, 162179.Google ScholarPubMed
Cheng, J, Tian, L, Ma, J, et al. (2015) Dying tumor cells stimulate proliferation of living tumor cells via caspase-dependent protein kinase C delta activation in pancreatic ductal adenocarcinoma. Mol Oncol 9, 105114.CrossRefGoogle ScholarPubMed
Bernard, A, Chevrier, S, Beltjens, F, et al. (2019) Cleaved caspase-3 transcriptionally regulates angiogenesis-promoting chemotherapy resistance. Cancer Res 79, 59585970.CrossRefGoogle ScholarPubMed
Johansson, M, Mattsson, G, Andersson, A, et al. (2006) Islet endothelial cells and pancreatic β-cell proliferation: studies in vitro and during pregnancy in adult rats. Endocrinology 147, 23152324.CrossRefGoogle ScholarPubMed
Klöppel, G, Löhr, M, Habich, K, et al. (1985) Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. Surv Synth Pathol Res 4, 110125.Google ScholarPubMed
Clark, A, Wells, CA, Buley, ID, et al. (1988) Islet amyloid, increased α-cells, reduced β-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res 9, 151159.Google Scholar
Rodríguez-Trejo, A, Ortiz-López, MG, Zambrano, E, et al. (2012) Developmental programming of neonatal pancreatic β-cells by a maternal low-protein diet in rats involves a switch from proliferation to differentiation. Am J Physiol Endocrinol Metab 302, E1431E1439.CrossRefGoogle ScholarPubMed

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