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Early postnatal stress impairs insulin secretion in response to psychological stress in adult rats

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Abstract

Purpose

Adversity in early life can induce metabolic defects in exposure to stress in adulthood. Therefore, the exploration of involving mechanisms can be helpful in the treatment of metabolic disorders. So, the present study was conducted in terms of exploring the effects of interaction between early postnatal stress and young adulthood psychological stress on insulin secretion and pancreatic GLUT-2 levels in male rats.

Methods

Footshock as a model of early life stress (at 2 weeks of age) and psychological stress induced by communication box as a model of young adulthood stress (at 8–10 weeks of age) were induced in male Wistar rats for five consecutive days (2 times/day). Blood samples were drawn to measure glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell dysfunction (HOMA-B), before and after stress protocol in young adult rats. Corticosterone was measured on days 1 and 5 of stress induction. The day after the stress period, factors including glucose tolerance, TNF-alpha, isolated islets’ insulin output and levels of pancreatic GLUT-2 protein via western blotting were determined.

Results

The combination of early footshock exposure and psychological stress during adulthood did not affect plasma corticosterone, but increased plasma insulin, HOMA-IR, HOMA-B and TNF-alpha levels. Plasma TNF was not only increased by the combination of both stressors, but also after only E STR exposure. HOMA-IR was increased in both Psy STR and E + Psy-STR groups. Plasma glucose just increased in Psy STR group. The combination of these two life stressors further increased the in vitro insulin secretion from isolated islets in response to 16.7-mM glucose. The level of Glut2 was increased in Psy STR and decreased in both E STR and E + Psy STR groups. Finally, glucose tolerance was impaired and glucose-stimulated insulin secretion was increased in E + Psy STR group.

Conclusions

In conclusion, inducing stress in early life makes the organism more susceptible to metabolic defects in exposure to psychological stress later in life.

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References

  1. Friedman EM, Karlamangla AS, Gruenewald T, Koretz B, Seeman TE (2015) Early life adversity and adult biological risk profiles. Psychosom Med 77(2):176

    PubMed  PubMed Central  Google Scholar 

  2. Ilchmann-Diounou H, Olier M, Lencina C, Riba A, Barretto S, Nankap M, Sommer C, Guillou H, Ellero-Simatos S, Guzylack-Piriou L (2019) Early life stress induces type 2 diabetes-like features in ageing mice. Brain Behav Immun 80:452–463

    CAS  PubMed  Google Scholar 

  3. Ruiz R, Roque A, Pineda E, Licona-Limón P, Valdéz-Alarcón JJ, Lajud N (2018) Early life stress accelerates age-induced effects on neurogenesis, depression, and metabolic risk. Psychoneuroendocrinology 96:203–211

    PubMed  Google Scholar 

  4. Vargas J, Junco M, Gomez C, Lajud N (2016) Early life stress increases metabolic risk, HPA axis reactivity, and depressive-like behavior when combined with postweaning social isolation in rats. PLoS ONE 11(9):e0162665

    PubMed  PubMed Central  Google Scholar 

  5. Santarelli S, Zimmermann C, Kalideris G, Lesuis SL, Arloth J, Uribe A, Dournes C, Balsevich G, Hartmann J, Masana M (2017) An adverse early life environment can enhance stress resilience in adulthood. Psychoneuroendocrinology 78:213–221

    PubMed  Google Scholar 

  6. Petersen MC, Shulman GI (2018) Mechanisms of insulin action and insulin resistance. Physiol Rev 98(4):2133–2223

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Nolan CJ, Prentki M (2019) Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: tTime for a conceptual framework shift. Diabetes Vasc Dis Res 16(2):118–127

    CAS  Google Scholar 

  8. Whirledge S, DeFranco DB (2017) Glucocorticoid signaling in health and disease: insights from tissue-specific GR knockout mice. Endocrinology 159(1):46–64

    PubMed Central  Google Scholar 

  9. Pedersen JM, Mortensen EL, Christensen DS, Rozing M, Brunsgaard H, Meincke RH, Petersen GL, Lund R (2018) Prenatal and early postnatal stress and later life inflammation. Psychoneuroendocrinology 88:158–166

    CAS  PubMed  Google Scholar 

  10. Pedersen JM, Lund R, Andersen I, Clark AJ, Prescott E, Rod NH (2016) Psychosocial risk factors for the metabolic syndrome: a prospective cohort study. Int J Cardiol 215:41–46

    PubMed  Google Scholar 

  11. Levine M, Cole S, Weir D, Crimmins E (2015) Childhood and later life stressors and increased inflammatory gene expression at older ages. Soc Sci Med 130:16–22

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Kim W-H, Lee JW, Suh YH, Hong SH, Choi JS, Lim JH, Song JH, Gao B, Jung MH (2005) Exposure to chronic high glucose induces β-cell apoptosis through decreased interaction of glucokinase with mitochondria: downregulation of glucokinase in pancreatic β-cells. Diabetes 54(9):2602–2611

    CAS  PubMed  Google Scholar 

  13. Navarro-Tableros V, Fiordelisio T, Hernández-Cruz A, Hiriart M (2007) Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat β-cells. Am J Physiol-Endocrinol Metab 292(4):E1018–E1029

    CAS  PubMed  Google Scholar 

  14. Farr OM, Ko B-J, Joung KE, Zaichenko L, Usher N, Tsoukas M, Thakkar B, Davis CR, Crowell JA, Mantzoros CS (2015) Posttraumatic stress disorder, alone or additively with early life adversity, is associated with obesity and cardiometabolic risk. Nutr Metab Cardiovas Dis 25(5):479–488

    CAS  Google Scholar 

  15. Nasca C, Watson-Lin K, Bigio B, Robakis TK, Myoraku A, Wroolie TE, McEwen BS, Rasgon N (2019) Childhood trauma and insulin resistance in patients suffering from depressive disorders. Exp Neurol 315:15–20

    CAS  PubMed  Google Scholar 

  16. Zardooz H, Zahediasl S, Rostamkhani F, Farrokhi B, Nasiraei S, Kazeminezhad B, Gholampour R (2012) Effects of acute and chronic psychological stress on isolated islets’ insulin release. EXCLI J 11:163

    PubMed  PubMed Central  Google Scholar 

  17. Matsumoto M, Higuchi K, Togashi H, Koseki H, Yamaguchi T, Kanno M, Yoshioka M (2005) Early postnatal stress alters the 5-HTergic modulation to emotional stress at postadolescent periods of rats. Hippocampus 15(6):775–781

    CAS  PubMed  Google Scholar 

  18. Andersen ML, Bignotto M, Machado RB, Tufik S (2004) Different stress modalities result in distinct steroid hormone responses by male rats. Braz J Med Biol Res 37(6):791–797

    CAS  PubMed  Google Scholar 

  19. Zardooz H, Asl SZ, Naseri MG (2006) Effect of chronic psychological stress on insulin release from rat isolated pancreatic islets. Life Sci 79(1):57–62

    CAS  PubMed  Google Scholar 

  20. Oosterlinck W, Vanderper A, Flameng W, Herijgers P (2011) Glucose tolerance and left ventricular pressure-volume relationships in frequently used mouse strains. BioMed Res Int 2011:1–7

    Google Scholar 

  21. Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419

    CAS  PubMed  Google Scholar 

  22. Krzyzanowska K, Zemany L, Krugluger W, Schernthaner G, Mittermayer F, Schnack C, Rahman R, Brix J, Kahn B, Schernthaner G (2008) Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes. Diabetologia 51(7):1115–1122

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Lacy PE, Kostianovsky M (1967) Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16(1):35–39

    CAS  PubMed  Google Scholar 

  24. Vélez-Granell CS, Arias AE, Torres-Ruíz JA, Bendayan M (1994) Molecular chaperones in pancreatic tissue: the presence of cpn10, cpn60 and hsp70 in distinct compartments along the secretory pathway of the acinar cells. J Cell Sci 107(3):539–549

    PubMed  Google Scholar 

  25. Ladd CO, Huot RL, Thrivikraman K, Nemeroff CB, Plotsky PM (2004) Long-term adaptations in glucocorticoid receptor and mineralocorticoid receptor mRNA and negative feedback on the hypothalamo-pituitary-adrenal axis following neonatal maternal separation. Biol Psychiat 55(4):367–375

    CAS  PubMed  Google Scholar 

  26. Lippmann M, Bress A, Nemeroff CB, Plotsky PM, Monteggia LM (2007) Long-term behavioural and molecular alterations associated with maternal separation in rats. Eur J Neurosci 25(10):3091–3098

    PubMed  Google Scholar 

  27. Ladd CO, Thrivikraman K, Huot RL, Plotsky PM (2005) Differential neuroendocrine responses to chronic variable stress in adult Long Evans rats exposed to handling-maternal separation as neonates. Psychoneuroendocrinology 30(6):520–533

    CAS  PubMed  Google Scholar 

  28. Eiland L, McEwen BS (2012) Early life stress followed by subsequent adult chronic stress potentiates anxiety and blunts hippocampal structural remodeling. Hippocampus 22(1):82–91

    PubMed  Google Scholar 

  29. Fóscolo DRC, Fóscolo RB, Marubayashi U, Reis AM, Coimbra CC (2008) Neonatal maternal separation affects endocrine and metabolic stress responses to ether exposure but not to restraint exposure in adult rats. Metab Brain Dis 23(4):375

    PubMed  Google Scholar 

  30. Wu XY, Hu YT, Guo L, Lu J, Zhu QB, Yu E, Wu JL, Shi LG, Huang ML, Bao AM (2015) Effect of pentobarbital and isoflurane on acute stress response in rat. Physiol Behav 145(1):118–121

    CAS  PubMed  Google Scholar 

  31. De Boer S, Slangen J, Van der Gugten J (1988) Adaptation of plasma catecholamine and corticosterone responses to short-term repeated noise stress in rats. Physiol Behav 44(2):273–280

    PubMed  Google Scholar 

  32. McPherson RJ, Mascher-Denen M, Juul SE (2009) Postnatal stress produces hyperglycemia in adult rats exposed to hypoxia-ischemia. Pediatr Res 66(3):278

    CAS  PubMed  Google Scholar 

  33. Teague CR, Dhabhar FS, Barton RH, Beckwith-Hall B, Powell J, Cobain M, Singer B, McEwen BS, Lindon JC, Nicholson JK (2007) Metabonomic studies on the physiological effects of acute and chronic psychological stress in sprague− dawley rats. J Proteome Res 6(6):2080–2093

    CAS  PubMed  Google Scholar 

  34. Eguchi R, Scarmagnani FR, Cunha CA, Souza GI, Pisani LP, Ribeiro EB, do Nascimento CMO, Spadari-Bratfisch RC, Oyama LM (2011) Fish oil consumption prevents glucose intolerance and hypercorticosteronemy in footshock-stressed rats. Lipids Health Dis 10(1):7

    Google Scholar 

  35. Wilcox G (2005) Insulin and insulin resistance. Clin Biochemist Rev 26(2):19

    Google Scholar 

  36. Wang Y, Nishi M, Doi A, Shono T, Furukawa Y, Shimada T, Furuta H, Sasaki H, Nanjo K (2010) Ghrelin inhibits insulin secretion through the AMPK–UCP2 pathway in β cells. FEBS Lett 584(8):1503–1508

    CAS  PubMed  Google Scholar 

  37. Liu Y-Z, Wang Y-X, Jiang C-L (2017) Inflammation: the common pathway of stress-related diseases. Front Hum Neurosci 11:316

    PubMed  PubMed Central  Google Scholar 

  38. Pruett SB (2003) Stress and the immune system. Pathophysiology 9(3):133–153

    CAS  PubMed  Google Scholar 

  39. Li J, Bai L, Wei F, Zhao J, Wang D, Xiao Y, Yan W, Wei J (2019) Therapeutic mechanisms of herbal medicines against insulin resistance: a review. Front pharmacol 10:661

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Pittas AG, Joseph NA, Greenberg AS (2004) Adipocytokines and insulin resistance. J Clin Endocrinol Metab 89(2):447–452

    CAS  PubMed  Google Scholar 

  41. Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS, Turner RB (2012) Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci 109(16):5995–5999

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Hohmann CF, Odebode G, Naidu L, Koban M (2017) Early life stress alters adult inflammatory responses in a mouse model for depression. Ann Psychiatry Mental Health 5(2):1–12

    Google Scholar 

  43. Fagundes CP, Way B (2014) Early-life stress and adult inflammation. Curr Dir Psychol Sci 23(4):277–283

    Google Scholar 

  44. Veenema AH, Reber SO, Selch S, Obermeier F, Neumann ID (2008) Early life stress enhances the vulnerability to chronic psychosocial stress and experimental colitis in adult mice. Endocrinology 149(6):2727–2736

    CAS  PubMed  Google Scholar 

  45. Alvarez P, Green PG, Levine JD (2013) Stress in the adult rat exacerbates muscle pain induced by early-life stress. Biol Psychiat 74(9):688–695

    CAS  PubMed  Google Scholar 

  46. Courty E, Besseiche A, Do TTH, Liboz A, Aguid FM, Quilichini E, Buscato M, Gourdy P, Gautier J-F, Riveline J-P (2019) Adaptive β-cell neogenesis in the adult mouse in response to glucocorticoid-induced insulin resistance. Diabetes 68(1):95–108

    CAS  PubMed  Google Scholar 

  47. Guillam M-T, Hümmler E, Schaerer E, Wu J-Y, Birnbaum MJ, Beermann F, Schmidt A, Dériaz N, Thorens B (1997) Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat Genet 17(3):327

    CAS  PubMed  Google Scholar 

  48. Tal M, Wu YJ, Leiser M, Surana M, Lodish H, Fleischer N, Weir G, Efrat S (1992) [Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis. Proc Natl Acad Sci 89(13):5744–5748

    CAS  PubMed  PubMed Central  Google Scholar 

  49. De Vos A, Heimberg H, Quartier E, Huypens P, Bouwens L, Pipeleers D, Schuit F (1995) Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression. J Clin Invest 96(5):2489–2495

    PubMed  PubMed Central  Google Scholar 

  50. Gluckman PD, Hanson MA, Cooper C, Thornburg KL (2008) Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 359(1):61–73

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Dhar A, Dhar I, Jiang B, Desai KM, Wu L (2011) Chronic methylglyoxal infusion by minipump causes pancreatic β-cell dysfunction and induces type 2 diabetes in Sprague-Dawley rats. Diabetes 60(3):899–908

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Dr. Hossein Khaleghzadeh-Ahangar, the Assistant Professor at Babol University of Medical Sciences for his aid in English editing. This work was supported by Diabetes Research Center (Grant 3069).

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Authors and Affiliations

  1. Department of Physiology and Neurophysiology Research Center, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    H. Zardooz

  2. Department of Physiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    F. Sadeghimahalli

  3. Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    F. Sadeghimahalli

  4. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    F. Khodagholi

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  1. H. Zardooz
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Correspondence to F. Sadeghimahalli.

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All procedures were approved by the Animal Care and Use Committee of the Diabetes Research Center of Research Deputy of Mazandaran University of Medical Sciences, Sari, Iran.

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Zardooz, H., Sadeghimahalli, F. & Khodagholi, F. Early postnatal stress impairs insulin secretion in response to psychological stress in adult rats. J Endocrinol Invest 44, 277–286 (2021). https://doi.org/10.1007/s40618-020-01291-9

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