Journal of Diabetes & Metabolic Disorders Category: Clinical Type: Research Article
Role of Glucocorticoids and Stress in Pathogeny of Diabetes Mellitus and Related Disorders
- Viktor Ivanovitch Goudochnikov1*
- 1 Council Of International Society For Dohad, Santa Maria, Rio Grande Do Sul, Brazil
*Corresponding Author:Viktor Ivanovitch Goudochnikov
Council Of International Society For Dohad, Santa Maria, Rio Grande Do Sul, Brazil
Received Date: Dec 12, 2017 Accepted Date: Apr 16, 2018 Published Date: Apr 30, 2018
Presented work aimed at preparing literature review that could describe the contribution of Glucocorticoids (GC) and stress to pathogeny of diabetes mellitus and related disorders: Metabolic syndrome and obesity. This review includes the following topics: Effects of GC and stress on glucose metabolism, the role of GC and stress in pathogenetic mechanisms of clinical and experimental diabetes, the importance of catecholamines and other stress hormones in mechanisms of hypo and hyperglycemia, interactions of GC with high-fat diet, contribution of GC to comorbidity of metabolic and neuropsychiatric disorders, metabolic consequences of prolonged GC treatment, the role of GC in programming/imprinting phenomena, the importance of stress proteins in pathogeny of metabolic disorders and modes of counteracting stress and GC in diabetes and related diseases. The conclusion is made about the necessity of more detailed evaluation of the effects of hormones having antistress properties, as applied to metabolic disorders.
BDNF: Brain Derived Neurotrophic Factor
DOHaD: Developmental Origins of Health and Disease
DST: Dexamethasone Suppression Test
HPA: Hypothalamo Pituitary Adrenal (axis)
HSP: Heat Shock Proteins
iHSP70: Intracellular Hsp70
eHSP70: Extracellular HSP70
eHSP72: Extracellular HSP72
PEPCK: Phosphoenolpyruvate Carboxykinase
PPAR-alpha: Peroxysome Proliferator-Activated Receptor, Type Alpha
PPAR-gamma: Peroxysome Proliferator-Activated Receptor, Type Gamma
SAMS: Sympatho Adrenomedullary System
11beta-HSD1: 11beta-Hydroxysteroid Dehydrogenase Type 1
Earlier we have briefly discussed the role of Glucocorticoids (GC) in mechanisms of aging and age-related diseases [1,2]. During such discussion it became clear that it is necessary to describe in more details the role of GC and stress in pathogeny of various diseases. Therefore, the presented work aimed at preparing literature review about the contribution of GC and stress to pathogeny of diabetes mellitus and related disorders, especially metabolic syndrome and obesity. Our choice of GC from the whole spectrum of stress hormones was justified, on one hand, by central positions occupied by GC in metabolic bioregulation and on the other hand, by the broad use of GC in various subfields of medicine as pharmacotherapeutic preparations, mainly with anti-inflammatory and immunosuppressive action. Therefore, it is necessary to consider possible diabetogenic GC action on patients with non-endocrine disorders.
MATERIALS AND METHODS
Two types of stress as related to stress hormones and proteins
Effects of glucocorticoids and stress on parameters of glucose metabolism
Role of glucocorticoids and stress in pathogenetic mechanisms of clinical diabetes, metabolic syndrome and obesity
The role of catecholamines and other stress hormones in mechanisms of hypo and hyperglycemia, as well as other metabolic disorders
Role of glucocorticoids and stress in pathogeny of experimental diabetes and metabolic disturbances related to high-fat diet
Role of glucocorticoids in comorbidities of metabolic and neuropsychiatric disorders
Metabolic consequences of pharmacotherapy with exogenous glucocorticoids
Role of glucocorticoids in phenomena of programming/imprinting of metabolic disorders
The importance of stress proteins in pathogeny of metabolic disorders
Modes of counteracting stress and glucocorticoids as possible means of treatment of metabolic disorders
The author is grateful to unknown reviewers for valuable suggestions that allowed to greatly improve the final version of this manuscript.
CONFLICT OF INTEREST
The author affirms that conflict of interests related to this work does not exist.
- Goudochnikov VI (2011) The role of glucocorticoids in aging and age-related pharmacotherapy. Adv Gerontol 24: 48-53.
- Goudochnikov VI (2010) Stress mediators in pathogeny of age-related diseases. In: 10th ISMA-BR Congress of Stress. Porto Alegre, Brazil.
- Strack AM, Sebastian RJ, Schwartz MW, Dallman MF (1995) Glucocorticoids and insulin: Reciprocal signals for energy balance. Am J Physiol 268: 142-149.
- Tappy L, Randin D, Vollenweider P, Vollenweider L, Paquot N, et al. (1994) Mechanisms of dexamethasone-induced insulin resistance in healthy humans. J Clin Endocrinol Metab 79: 1063-1069.
- Andrews RC, Walker BR (1999) Glucocorticoids and insulin resistance: Old hormones, new targets. Clin Sci (Lond) 96: 513-523.
- Surwit RS, Schneider MS (1993) Role of stress in the etiology and treatment of diabetes mellitus. Psychosom Med 55: 380-393.
- Heraclides A, Chandola T, Witte DR, Brunner EJ (2009) Psychosocial stress at work doubles the risk of type 2 diabetes in middle-aged women: Evidence from the Whitehall II study. Diabetes Care 32: 2230-2235.
- Chiodini I, Adda G, Scillitani A, Coletti F, Morelli V, et al. (2007) Cortisol secretion in patients with type 2 diabetes: Relationship with chronic complications. Diabetes Care 30: 83-88.
- Lloyd C, Smith J, Weinger K (2005) Stress and diabetes: A review of the links. Diabetes Spectrum 18: 121-127.
- Bitar MS (1998) Glucocorticoid dynamics and impaired wound healing in diabetes mellitus. Am J Pathol 152: 547-554.
- Rowland NE, Bellush LL (1989) Diabetes mellitus: Stress, neurochemistry and behavior. Neurosci Biobehav Rev 13: 199-206.
- Brunner EJ, Hemingway H, Walker BR, Page M, Clarke P, et al. (2002) Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: Nested case-control study. Circulation 106: 2659-2665.
- Wang M (2005) The role of glucocorticoid action in the pathophysiology of the metabolic syndrome. Nutr Metab (Lond) 2: 3.
- Rask E, Olsson T, Soderberg S, Andrew R, Livingstone DE, et al. (2001) Tissue-specific dysregulation of cortisol metabolism in human obesity. J Clin Endocrinol Metab 86: 1418-1421.
- Roberge C, Carpentier AC, Langlois MF, Baillargeon JP, Ardilouze JL, et al. (2007) Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity. Am J Physiol Endocrinol Metab 293: 1465-1478.
- Ehrmann DA, Breda E, Corcoran MC, Cavaghan MK, Imperial J, et al. (2004) Impaired beta-cell compensation to dexamethasone-induced hyperglycemia in women with polycystic ovary syndrome. Am J Physiol Endocrinol Metab 287: 241-246.
- Cryer PE (2001) Hypoglycemia-associated autonomic failure in diabetes. Am J Physiol 281: 1115-1121.
- Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC (2001) Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: A systematic overview. Stroke 32: 2426-2432.
- Nirupama R, Devaki M, Yajurvedi HN (2012) Chronic stress and carbohydrate metabolism: Persistent changes and slow return to normalcy in male albino rats. Stress 15: 262-271.
- Vaccarino V, Bremner JD (2005) Stress response and the metabolic syndrome. Hospital Physician 11.
- Mead VP (2004) A new model for understanding the role of environmental factors in the origins of chronic illness: A case study of type 1 diabetes mellitus. Med Hypotheses 63: 1035-1046.
- Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, et al.(2008) Diabetes impairs hippocampal function via glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci 11: 309-317.
- Magarinos AM, McEwen BS (2000) Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. Proc Natl Acad Sci U S A 97: 11056-11061.
- Revsin Y, Rekers NV, Louwe MC, Saravia FE, De Nicola AF, et al. (2009) Glucocorticoid receptor blockade normalizes hippocampal alteractions and cognitive impairment in streptozotocin-induced type I diabetes mice. Neuropsychopharmacology 34: 747-758.
- Rubinstein MR, Cremaschi GA, Oliveri LM, Gerez EN, Wald MR, et al. (2010) Possible involvement of stress hormones and hyperglycaemia in chronic mild stress-induced impairment of immune functions in diabetic mice. Stress 13: 384-391.
- Revsin Y, de Kloet ER (2009) When glucocorticoids change from protective to harmful: Lessons from a type 1 diabetes animal model. Medicina 69: 353-358.
- Sivabalan S, Renuka S, Menon VP (2008) Fat feeding potentiates the diabetogenic effect of dexamethasone in Wistar rats. Int Arch Med 1: 7.
- Shpilberg Y, Beaudry JL, D’Souza A, Campbell JE, Peckett A, et al. (2012) A rodent model of rapid-onset diabetes induced by glucocorticoids and high-fat feeding. Dis Model Mech 5: 671-680.
- Nieuwenhuizen AG, Rutters F (2008) The hypothalamic-pituitary-adrenal axis in the regulation of energy balance. Physiol Behav 94: 169-177.
- Duong M, Cohen JI, Convit A (2012) High cortisol levels are associated with low quality food choice in type 2 diabetes. Endocrine 41: 76-81.
- Gragnoli C (2014) Hypothesis of the neuroendocrine cortisol pathway gene role in the comorbidity of depression, type 2 diabetes, and metabolic syndrome. Appl Clin Genet 7: 43-53.
- Bornstein SR, Schuppenies A, Wong ML, Licinio J (2006) Approaching the shared biology of obesity and depression: The stress axis as the locus of gene-environment interactions. Mol Psychiatry 11: 892-902.
- Rustad JK, Musselman DL, Nemeroff CB (2011) The relationship of depression and diabetes: Pathophysiological and treatment implications. Psychoneuroendocrinology 36: 1276-1286.
- Reagan LP (2012) Diabetes as a chronic metabolic stressor: Causes, consequences and clinical complications. Exp Neurol 233: 68-78.
- Brietzke E, Kapczinski F, Grassi-Oliveira R, Grande I, Vieta E, et al. (2011) Insulin dysfunction and allostatic load in bipolar disorder. Expert Rev Neurother 11: 1017-1028.
- Dinan TG (2004) Stress and the genesis of diabetes mellitus in schizophrenia. Br J Psychiatry Suppl 47: 72-75.
- Di Dalmazi G, Pagotto U, Pasquali R, Vicennati V (2012) Glucocorticoids and type 2 diabetes: From physiology to pathology. J Nutr Metab 2012: 525093.
- Gulliford MC, Charlton J, Latinovic R (2006) Risk of diabetes associated with prescribed glucocorticoids in a large population. Diabetes Care 29: 2728-2729.
- Beaudry JL, Riddel MC (2012) Effects of glucocorticoids and exercise on pancreatic beta-cell function and diabetes development. Diabetes Metab Res Rev 28: 560-573.
- Bernal-Mizrachi C, Weng S, Feng C, Finck BN, Knutsen RH, et al. (2003) Dexamethasone induction of hypertension and diabetes is PPAR-alpha dependent in LDL receptor-null mice. Nat Med 9: 1069-1075.
- Leipala JA, Raivio KO, Sarnesto A, Panteleon A, Fellman V (2002) Intrauterine growth restriction and postnatal steroid treatment effects on insulin sensitivity in preterm neonates. J Pediatr 141: 472-476.
- Nyirenda MJ, Lindsay RS, Kenyon CJ, Burchell A, Seckl JR (1998) Glucocorticoid exposure in late gestation permanently programs rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring. J Clin Invest 101: 2174-2181.
- Lesage J, Del-Favero F, Leonhardt M, Louvart H, Maccari S, et al. (2004) Prenatal stress induces intrauterine growth restriction and programmes glucose intolerance and feeding behavior disturbances in the aged rat. J Endocrinol 181: 291-296.
- Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP (2009) Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: A hypothesis. J Clin Endocrinol Metab 94: 2692-2701.
- Dzgoeva FK (2015) Intrauterine nutrition: Fetal programming of metabolic syndrome. Obes Metab 12: 10-17.
- Goudochnikov VI (2015) Role of stress proteins and hormones in bioregulation of ontogeny. Probl Endocrinol 61: 49-53.
- Hooper PL, Hooper JJ (2005) Loss of defense against stress: Diabetes and heat shock proteins. Diabetes Technol Ther 7: 204-208.
- Krause M, Heck TG, Bittencourt A, Scomazzon SP, Newsholme P, et al. (2015) The chaperone balance hypothesis: The importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management. Mediators Inflamm.
- Ludwig MS, Minguetti-Camara V, Heck TG, Scomazzon SP, Nunes PR, et al. (2014) Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats: An effect associated with IL-6 levels but not with IL-10 or TNF-alpha. Mol Cell Biochem 397: 97-107.
- Campbell J, Kiraly MA, Atkinson DJ, D’Souza AM, Vranic M, et al. (2010) Regular exercise prevents the development of hyperglucocorticoidemia via adaptations in the brain and adrenal glands in male Zucker diabetic fatty rats. Am J Physiol Regul Integr Comp Physiol 299: 168-176.
- Genolet P, Petite C, Petignat PA (2012) Diabete cortico-induit, une entite frequente sans prise en charge standardisee. Rev Med Suisse 8: 800-805.
- Sandeep TC, Yau JL, MacLullich AM, Noble J, Deary IJ, et al. (2004) 11beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics. Proc Natl Acad Sci U S A 101: 6734-6739.
- Apostolova G, Schweizer RA, Balazs Z, Kostadinova RM, Odermatt A (2005) Dehydroepiandrosterone inhibits the amplification of glucocorticoid action in adipose tissue. Am J Physiol Endocrinol Metab 288: 957-964.
- Stewart PM, Tomlinson JW (2009) Selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 for patients with metabolic syndrome. Is the target liver, fat, or both? Diabetes 58: 14-15.
- Rosenstock J, Banarer S, Fonseca VA, Inzucchi SE, Sun W, et al. et al. (2010) The 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor INCB 13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy. Diabetes Care 33: 1516-1522.
- Meerson FZ (1994) Stress-induced arrhythmic disease of the heart-part I. Clin Cardiol 17: 362-371.
- Vegiopoulos A, Herzig S (2007) Glucocorticoids, metabolism and metabolic diseases. Mol Cell Endocrinol 275: 43-61.
- Prokhorov LY, Goudochnikov VI (2015) Role of glucocorticoids and stress in bioregulation of redox homeostasis in development and aging. Klin Gerontol 21: 101-102.
- Goudochnikov VI (2015) Role of hormones in perinatal and early postnatal development: Possible contribution to programming/imprinting phenomena. Russ J Dev Biol 46: 237-245
- Prokhrov LY, Goudochnikov VI (2014) Ontogenetic role of melatonin and neuroactive steroids as antistress hormones. Gerontologiya 2: 157-180.
- Goudochnikov VI, Prokhorov LY (2014) Ontogenetic role of somatolactogens and related peptides as antistress hormones. Gerontologiya 2: 143-156.
- Black PH (2003) The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav Immun 17: 350-364.
- Gems D, Partridge L (2008) Stress-response hormesis and aging: “That which does not kill us makes us stronger”. Cell Metab 7: 200-203.
- Inder WJ, Obeyesekere VR, Jang C, Saffery R (2012) Evidence for transcript-specific epigenetic regulation of glucocorticoid-stimulated skeletal muscle 11β-hydroxysteroid dehydrogenase-1 activity in type 2 diabetes. Clin Epigenetics 4: 24.
- Crudo A, Petropoulos S, Suderman M, Moisiadis VG, Kostaki A, et al. (2013) Effects of antenatal synthetic glucocorticoid on glucocorticoid receptor binding, DNA methylation, and genome-wide mRNA levels in the fetal male hippocampus. Endocrinology 154: 4170-4181.
- Hunter RG, Gagnidze K, McEwen BS, Pfaff DW (2015) Stress and the dynamic genome: Steroids, epigenetics, and the transposome. Proc Natl Acad Sci U S A 112: 6828-6833.
Citation: Goudochnikov IV (2018) Role of Glucocorticoids and Stress in Pathogeny of Diabetes Mellitus and Related Disorders. J Diabetes Metab Disord 5: 022.
Copyright: © 2018 Viktor Ivanovitch Goudochnikov, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.