Maternal Low-Protein Diet During Nursing Leads to Glucose–Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male Rats
Both perinatal malnutrition and elevated glucocorticoids are pivotal triggers of the growing global pandemic of metabolic diseases. Here, we studied the effects of metabolic stress responsiveness on glucose–insulin homeostasis and pancreatic-islet function in male Wistar offspring whose mothers unde...
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2024-12-01
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| author | Paulo Cezar de Freitas Mathias Aline Milena Dantas Rodrigues Patrícia Cristina Lisboa Rosiane Aparecida Miranda Ananda Malta Tatiane Aparecida Ribeiro Luiz Felipe Barella Ginislene Dias Thalyne Aparecida Leite Lima Rodrigo Mello Gomes Egberto Gaspar de Moura Júlio Cezar de Oliveira |
| author_facet | Paulo Cezar de Freitas Mathias Aline Milena Dantas Rodrigues Patrícia Cristina Lisboa Rosiane Aparecida Miranda Ananda Malta Tatiane Aparecida Ribeiro Luiz Felipe Barella Ginislene Dias Thalyne Aparecida Leite Lima Rodrigo Mello Gomes Egberto Gaspar de Moura Júlio Cezar de Oliveira |
| author_sort | Paulo Cezar de Freitas Mathias |
| collection | DOAJ |
| description | Both perinatal malnutrition and elevated glucocorticoids are pivotal triggers of the growing global pandemic of metabolic diseases. Here, we studied the effects of metabolic stress responsiveness on glucose–insulin homeostasis and pancreatic-islet function in male Wistar offspring whose mothers underwent protein restriction during lactation. During the first two weeks after delivery, lactating dams were fed a low-protein (4% protein, LP group) or normal-protein diet (22.5% protein, NP group). At 90 days of age, male rat offspring were challenged with food deprivation (72 h of fasting), intracerebroventricular (icv) injection of dexamethasone (2 µL, 2.115 mmol/L) or chronic intraperitoneal injection of dexamethasone (1 mg/kg body weight/5 days). Body weight, food intake, intravenous glucose tolerance test (ivGTT) results, insulin secretion and biochemical parameters were assessed. LP rats did not display significant metabolic changes after long-term starvation (<i>p</i> > 0.05) or under the central effect of dexamethasone (<i>p</i> = 0.999). Chronic dexamethasone induced rapid hyperglycemia (~1.2-fold, <i>p</i> < 0.001) and hyperinsulinemia (NP: 65%; LP: 216%; <i>p</i> < 0.001), decreased insulin sensitivity (NP: ~2-fold; LP: ~4-fold; <i>p</i> < 0.001), reduced insulinemia (20%) and increased glycemia (35%) only in NP rats under ivGTT conditions (<i>p</i> < 0.001). Glucose and acetylcholine insulinotropic effects, as well as the muscarinic receptor antagonist response, were reduced by chronic dexamethasone only in pancreatic islets from NP rats (<i>p</i> < 0.05). The direct effect of dexamethasone on pancreatic islets reduced insulin secretion (NP: 60.2%, <i>p</i> < 0.001; LP: 33.8%, <i>p</i> < 0.001). Peripheral glucose–insulin dyshomeostasis and functional failure of pancreatic islets in LP rats, as evidenced by an impaired acute and chronic response to metabolic stress, may be due to excessive corticosterone action as a long-term consequence. |
| format | Article |
| id | doaj-art-177e532fd85c40f8a08ce05c28655ef2 |
| institution | DOAJ |
| issn | 2079-7737 |
| language | English |
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| spelling | doaj-art-177e532fd85c40f8a08ce05c28655ef22025-08-20T02:43:28ZengMDPI AGBiology2079-77372024-12-011312103610.3390/biology13121036Maternal Low-Protein Diet During Nursing Leads to Glucose–Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male RatsPaulo Cezar de Freitas Mathias0Aline Milena Dantas Rodrigues1Patrícia Cristina Lisboa2Rosiane Aparecida Miranda3Ananda Malta4Tatiane Aparecida Ribeiro5Luiz Felipe Barella6Ginislene Dias7Thalyne Aparecida Leite Lima8Rodrigo Mello Gomes9Egberto Gaspar de Moura10Júlio Cezar de Oliveira11Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringa, Maringá 87020-900, BrazilResearch Group on Perinatal Programming of Metabolic Diseases: DOHaD Paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop 78556-264, BrazilLaboratory of Endocrine Physiology, Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro 20550-013, BrazilLaboratory of Endocrine Physiology, Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro 20550-013, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringa, Maringá 87020-900, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringa, Maringá 87020-900, BrazilLaboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringa, Maringá 87020-900, BrazilResearch Group on Perinatal Programming of Metabolic Diseases: DOHaD Paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop 78556-264, BrazilResearch Group on Perinatal Programming of Metabolic Diseases: DOHaD Paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop 78556-264, BrazilLaboratory of Endocrine Physiology and Metabolism, Institute of Biological Sciences, Federal University of Goiás, Goiânia 74690-900, BrazilLaboratory of Endocrine Physiology, Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro 20550-013, BrazilResearch Group on Perinatal Programming of Metabolic Diseases: DOHaD Paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop 78556-264, BrazilBoth perinatal malnutrition and elevated glucocorticoids are pivotal triggers of the growing global pandemic of metabolic diseases. Here, we studied the effects of metabolic stress responsiveness on glucose–insulin homeostasis and pancreatic-islet function in male Wistar offspring whose mothers underwent protein restriction during lactation. During the first two weeks after delivery, lactating dams were fed a low-protein (4% protein, LP group) or normal-protein diet (22.5% protein, NP group). At 90 days of age, male rat offspring were challenged with food deprivation (72 h of fasting), intracerebroventricular (icv) injection of dexamethasone (2 µL, 2.115 mmol/L) or chronic intraperitoneal injection of dexamethasone (1 mg/kg body weight/5 days). Body weight, food intake, intravenous glucose tolerance test (ivGTT) results, insulin secretion and biochemical parameters were assessed. LP rats did not display significant metabolic changes after long-term starvation (<i>p</i> > 0.05) or under the central effect of dexamethasone (<i>p</i> = 0.999). Chronic dexamethasone induced rapid hyperglycemia (~1.2-fold, <i>p</i> < 0.001) and hyperinsulinemia (NP: 65%; LP: 216%; <i>p</i> < 0.001), decreased insulin sensitivity (NP: ~2-fold; LP: ~4-fold; <i>p</i> < 0.001), reduced insulinemia (20%) and increased glycemia (35%) only in NP rats under ivGTT conditions (<i>p</i> < 0.001). Glucose and acetylcholine insulinotropic effects, as well as the muscarinic receptor antagonist response, were reduced by chronic dexamethasone only in pancreatic islets from NP rats (<i>p</i> < 0.05). The direct effect of dexamethasone on pancreatic islets reduced insulin secretion (NP: 60.2%, <i>p</i> < 0.001; LP: 33.8%, <i>p</i> < 0.001). Peripheral glucose–insulin dyshomeostasis and functional failure of pancreatic islets in LP rats, as evidenced by an impaired acute and chronic response to metabolic stress, may be due to excessive corticosterone action as a long-term consequence.https://www.mdpi.com/2079-7737/13/12/1036lactationundernutritionglucocorticoidsinsulin resistanceinsulin secretion |
| spellingShingle | Paulo Cezar de Freitas Mathias Aline Milena Dantas Rodrigues Patrícia Cristina Lisboa Rosiane Aparecida Miranda Ananda Malta Tatiane Aparecida Ribeiro Luiz Felipe Barella Ginislene Dias Thalyne Aparecida Leite Lima Rodrigo Mello Gomes Egberto Gaspar de Moura Júlio Cezar de Oliveira Maternal Low-Protein Diet During Nursing Leads to Glucose–Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male Rats Biology lactation undernutrition glucocorticoids insulin resistance insulin secretion |
| title | Maternal Low-Protein Diet During Nursing Leads to Glucose–Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male Rats |
| title_full | Maternal Low-Protein Diet During Nursing Leads to Glucose–Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male Rats |
| title_fullStr | Maternal Low-Protein Diet During Nursing Leads to Glucose–Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male Rats |
| title_full_unstemmed | Maternal Low-Protein Diet During Nursing Leads to Glucose–Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male Rats |
| title_short | Maternal Low-Protein Diet During Nursing Leads to Glucose–Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male Rats |
| title_sort | maternal low protein diet during nursing leads to glucose insulin dyshomeostasis and pancreatic islet dysfunction by disrupting glucocorticoid responsiveness in male rats |
| topic | lactation undernutrition glucocorticoids insulin resistance insulin secretion |
| url | https://www.mdpi.com/2079-7737/13/12/1036 |
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