RESUMO
This study was designed to investigate the HPA-axis impairment in the streptozotocin (STZ)-diabetic gerbils (Gerbillus gerbillus). Twenty-six male gerbils (body weight ~27 g) were divided into 3 groups: vehicle control (n = 10), 2 days of diabetes (n = 09) and 30 days of diabetes (n = 07). The latter 2 groups received an intraperitoneal injection of STZ (150 mg/kg of body weight). At 2 and 30 days of diabetes, streptozotocin-diabetic gerbils underwent a retro-orbital puncture for assessment of biochemical and hormonal parameters. Subsequently the animals were decapitated and the adrenal glands were removed, weighed and processed for light microscopy and stereology. Nondiabetic control gerbils that had been injected with citrate buffer were examined as a comparison. At 2 days of diabetes, STZ gerbils exhibited symptoms that are characteristic of human diabetes type 1. The adrenal gland showed significant increase in weight, associated with a larger cortex layer, hypertrophy of the fasciculate cells and a significant decrease in the nucleocytoplasmic index. These changes were associated with higher plasma ACTH and cortisol concentrations compared to nondiabetic controls. At 30 days postdiabetes, ACTH levels remained elevated, whereas cortisol levels decreased compared to the early stage of diabetes. Histological analysis revealed the existence of a band of connective tissue (collagen) that separates the cortical and medullary zones and is not present in humans or laboratory rodents, which represents a striking change seen throughout the disease. STZ-induced diabetes mellitus in Gerbillus gerbillus resulted in hyperactivation of the HPA axis in the early stages of diabetes mellitus which did not persist into the final stages of the disease, suggesting a possible reduction in adrenocortical sensitivity over time.
Assuntos
Diabetes Mellitus Tipo 1/patologia , Sistema Hipotálamo-Hipofisário/patologia , Sistema Hipófise-Suprarrenal/patologia , Estreptozocina/farmacologia , Animais , Peso Corporal/fisiologia , Corticosterona/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/induzido quimicamente , Gerbillinae/fisiologia , Insulina/metabolismo , MasculinoRESUMO
The aim of our study was to reveal the effects of long-term consumption of a high-carbohydrate diet (HCD) on metabolic dysfunctions and histopathological liver alterations in Gerbillus tarabuli, as well as to assess the preventive effects of 20-hydroxyecdysone (20E) in the same animals. Contrary to control diet, HCD induces several metabolic disorders including increased adiposity, dyslipidemia, ectopic fat deposition in the liver, associated with higher levels of plasma AST and ALT. These gerbils showed enhanced oxidative stress with liver damages characteristic of steatohepatitis development. By contrast, adding 20E to HCD resulted in a dose-dependent reduction of all changes induced by HCD. In addition, the hepatoprotective effect of 20E was demonstrated by decreased plasma concentrations of AST, ALT and of hepatic malondialdehyde. Our results suggest that G. tarabuli represents a good model to study diet-induced metabolic disorders and hepatic dysfunctions. Moreover, they demonstrate the efficacy of 20E treatment to counteract the damaging effects of HCD.
Assuntos
Dieta da Carga de Carboidratos/efeitos adversos , Ecdisterona/farmacologia , Doenças Metabólicas/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Gerbillinae , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
Obesity is associated with several endocrine disorders, including hypersensitivity of the hypothalamic-pituitary-adrenal axis. The aim of this study was to investigate the effects of a high carbohydrate diet on structural and ultrastructural features of steroidogenic tissue, as well to evaluate adrenocorticotropic hormone (ACTH), cortisol, and insulin levels in the blood and steroidogenic acute regulatory protein (StAR) expression in the adrenals of gerbils. In electron microscopy, the most pronounced effect of the hypercaloric diet was observed in the zona fasciculata. Plasma levels of ACTH, cortisol, and insulin also showed significant increases. However, no significant change was noted in StAR protein levels. There is evidence that high carbohydrate intake brings about remarkable morphological and functional modifications. This could ultimately lead to mitochondrial alteration and accumulation of lipid droplets, which may lead to inflammation and degeneration of adrenal cells.
Assuntos
Córtex Suprarrenal/patologia , Glândulas Suprarrenais/metabolismo , Obesidade/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Carboidratos da Dieta/administração & dosagem , Feminino , Gerbillinae/metabolismo , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Fosfoproteínas/metabolismo , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
The present work was aimed at studying the effects of streptozotocin (STZ; 130â¯mg/kg) in the desert gerbil, Gerbillus gerbillus, and at evaluating the impact of the short-term administration of 20-hydroxyecdysone (20E; 5â¯mg/kg). We observed that administration of streptozotocin caused a significant increase in plasmatic glucose and a decrease in insulin levels. The plasma lipid profile and liver glycogen content were also altered. The activities of antioxidant enzymes and malondialdehyde (MDA) levels were increased in the pancreatic tissue of STZ-treated gerbils. Moreover, histopathological and immunohistochemical analysis showed degenerative damage in the pancreas with a decline in the percentage area of ß-cells. Treatment of STZ-treated gerbils with 20E counteracted metabolic disorders and reduced lipid peroxidation. Histological and immunohistochemical studies showed moderate amelioration in the pancreatic structure. These findings indicate that streptozotocin administration induced experimental diabetes in gerbils and that short-term administration of 20E has beneficial effects in glucose homeostasis in STZ-treated gerbils suggesting that 20E may stimulate surviving ß-cells to release more insulin.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ecdisterona/administração & dosagem , Ecdisterona/uso terapêutico , Gerbillinae/fisiologia , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Ecdisterona/farmacologia , Glicogênio/metabolismo , Insulina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , EstreptozocinaRESUMO
A high intake of sugars has been linked to diet-induced health problems. The aim of this study was to assess whether the long-term consumption of a high-carbohydrate diet (HCD) would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH) in a desert gerbil, Gerbillus gerbillus. Compared to natural diet, HCD leads to several metabolic disorders including adiposity, dyslipidemia, insulin resistance, ectopic fat deposition in the liver, which were associated with higher levels of transcripts of genes involved with fat synthesis, endoplasmic reticulum (ER) stress, and fibrosis. In the same way, the experimented animals showed enhanced oxidative stress. Taken together, these results demonstrate that HCD consumption in gerbils induces metabolic disorders and damaged liver, which are key contributors to NASH development. These results suggest that this rodent represents a valuable natural model for human diet-induced metabolic disorders and nonalcoholic fatty liver disease (NAFLD).
Assuntos
Carboidratos da Dieta/toxicidade , Gerbillinae/fisiologia , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Adiposidade/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Dieta , Dislipidemias/sangue , Dislipidemias/induzido quimicamente , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Resistência à Insulina , Peroxidação de Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/patologia , Tamanho do Órgão/efeitos dos fármacos , Estresse OxidativoRESUMO
It is well established that, upon changing their natural desert low caloric (succulent halophilic plants) to a regular laboratory high caloric diet, sand rats undergo various phenotypic changes depending on their genetic background and including obesity and various degrees of insulin resistance. Our aim was to investigate the acute effects of Interleukin-1ß (IL-1ß) and Interferon-γ (IFN-γ) on glucose-induced insulin secretion in normal lean sand rats maintained on their natural diet and in obese insulin resistant normoglycemic or type 2 diabetic animals after a 9-month high caloric diet. Animals were fed either a low or a high caloric diet; after 9 months, pancreatic islets were isolated and incubated in the presence of increasing cytokine concentrations. At the end of the high-energy diet, animals were all over-weight, and probably due to a different genetic background, they displayed either insulin resistance, hyperinsulinemia and normoglycemia or a marked type-2 diabetic state. Pancreatic islets from obese insulin resistant normoglycemic animals were much more sensitive and responsive to IL-1ß when compared to lean controls. The cytokine was inefficient in diabetic islets. In conclusion, the markedly increased insulinotropic effect of IL-1ß in obese diabetes-resistant sand rat could participate and be involved in pancreatic ß-cell hyperactivity that compensates for insulin resistance and thereby prevent the development of type 2 diabetes in these animals.