RESUMO
Background/aim: Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are still being tried. The positive effects of metformin (MET) and physical exercise (EXE) on the pathophysiology of diabetes are well known. In this study, it was aimed to detail these positive effects of MET and EXE in combination on the basis of inflammation, apoptosis mechanisms, and endogen nesfatin-1 (NES-1) synthesis. Materials and methods: Twenty-seven type 2 DM (DM-2) male Wistar Albino rats were divided into 4 groups, as the high-fat diet (HFD), MET, EXE, and MET+EXE groups. The total duration of the study was 3 months. At the end of the experiment, blood glucose and lipid profiles were measured. Histopathological evaluation was performed on the cardiac and aortic tissues and apoptotic markers were evaluated immunohistochemically. Inflammatory markers and NES-1 levels were analyzed by enzyme-linked immunosorbent assay. Results: The plasma glucose, homeostatic model evaluation-insulin resistance (HOMA-IR), low-density lipoprotein (LDL) levels increased, and high-density lipoprotein (HDL) levels decreased significantly in the HFD group. In the treatment groups, the glucose, HOMA-IR, LDL, NES-1 levels in the plasma, as well as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-6, caspase-3 (Cas-3), Bcl-2-associated X protein (Bax), and histopathological findings of inflammation in tissues were decreased. Additionally, there was an increase in plasma insulin, HDL, and tissue B-cell lymphoma-2 and levels. Conclusion: It was observed that the MET and EXE treatments in the DM-2 model reduced cellular damage mechanisms such as inflammation and apoptosis. The decrease in NES-1 levels was thought to be secondary to this antiinflammatory effect. In conclusion, the results demonstrated the effectiveness of EXE in reducing DM-2 and the NES-1 levels. Further studies are needed to evaluate the effect in different EXE models and treatment durations.
Assuntos
Diabetes Mellitus Tipo 2 , Dieta Hiperlipídica , Metformina , Proteínas Proto-Oncogênicas c-bcl-2 , Ratos Wistar , Transdução de Sinais , Natação , Proteína X Associada a bcl-2 , Animais , Metformina/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Natação/fisiologia , Proteína X Associada a bcl-2/metabolismo , Obesidade/complicações , Condicionamento Físico Animal/fisiologia , Hipoglicemiantes/farmacologia , Apoptose/efeitos dos fármacos , Aorta/efeitos dos fármacos , Nucleobindinas , Diabetes Mellitus Experimental/complicaçõesRESUMO
The aim of this study was to examine pancreatic lesions and the possible prophylactic effects of agomelatine (AGO) in lipopolysaccharide (LPS)-induced sepsis in rats. Twenty-four female, 1-year-old Wistar albino rats were divided into three groups: group I (control), group II (study group; 5 mg/kg LPS i.p., single dose), and group III (treatment group; LPS + AGO, single dose p.o., 20 mg/kg AGO + 5 mg/kg LPS, 30 minutes after AGO treatment). The rats were sacrificed six hours after LPS administration. At the necropsy, blood and pancreatic tissue samples were collected for biochemical, pathological, and immunohistochemical analyses. The results showed that LPS caused an increase in serum amylase and lipase levels and a decrease in glucose levels. Histopathological analysis revealed infiltration of numerous neutrophils in pancreatic interstitial tissue and in vessels. In addition, slight vacuoles indicating degenerative changes were observed in endocrine and exocrine pancreatic tissues. Increased caspase-8, haptoglobin (Hp), IL-4, and IL-10 and decreased SIRT-1 expression was observed in both endocrine and exocrine parts of the pancreas in the LPS group. AGO ameliorated the biochemical, histopathological, and immunohistochemical findings. The present study results revealed that LPS-induced pancreatic damage to both endocrine and exocrine cells. In contrast, AGO had ameliorative effects on both biochemical and pathological findings in rats.
Assuntos
Lipopolissacarídeos , Pâncreas , Acetamidas , Animais , Feminino , Lipopolissacarídeos/toxicidade , Ratos , Ratos WistarRESUMO
Osteocalcin (OC) is inversely related to body fat distribution and fasting glucose levels. We sought to observe the effect of OC on fat distribution and subclinical atherosclerosis as measured by carotid intima-media thickness (CIMT) in premenopausal obese women. In this prospective observational study, totally, 73 premenopausal obese women (aged 17-55 years) and 53 healthy women (aged 20-50 years) with normal weight were included as controls. Anthropometric measurements, total fat and fat ratio, insulin, fasting blood glucose, and OC levels were estimated. Ultrasonography was used to assess fat distribution, and fat thickness was measured in 4 regions. Subcutaneous fat (SCF), visceral fat (VF), and preperitoneal fat (PPF) thicknesses were considerably higher in obese subjects (p<0.01) than healthy controls, while OC levels were significantly lower. No correlation was observed between OC levels and SCF, VF, or PPF. In a multiple regression analysis, OC was significantly positively associated with SCF (p=0.04, Beta=0.284). No associations were observed between OC levels and VF, PPF, or CIMT. A significant association was observed between parathyroid hormone (PTH) and VF (p=0.021, Beta=0.284), and vitamin D levels were inversely associated with VF (p=0.002, r=-0.366). OC levels were lower in premenopausal obese women than normal-weight healthy controls, but OC exhibited no correlation with VF or PPF, and only a weak positive association with SCF. Additionally, VF was positively correlated with PTH and inversely correlated with vitamin D. These results suggest that OC may be an early indicator of lipid accumulation in te subcutaneous area and development of atherosclerosis.
Assuntos
Distribuição da Gordura Corporal , Espessura Intima-Media Carotídea , Obesidade/sangue , Osteocalcina/sangue , Tecido Adiposo/diagnóstico por imagem , Adolescente , Adulto , Biomarcadores/sangue , Osso e Ossos/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Estudos Prospectivos , Ultrassonografia , Adulto JovemRESUMO
OBJECTIVES: Chronic consumption of high-fructose corn syrup (HFCS) causes several problems such as insulin resistance. The goal of the study was to investigate pancreatic damage induced by chronic HFCS consumption and the protective effects of alpha lipoic acid (ALA) on pancreatic cells. METHODS: Wistar Albino, 4-month-old, female rats weighing 250-300 g were randomly distributed into three groups, each containing eight rats. The study included an HFCS group, an HFCS + ALA-administered group and a control group (CON). The prepared 30% solution of HFCS (F30) (24% fructose, 28% dextrose) was added to the drinking water for 10 weeks. ALA treatment was begun 4 weeks after the first HFCS administration (100 mg/kg/oral, last 6 weeks). Rats were anaesthetised and euthanised by cervical dislocation 24 h after the last ALA administration. Blood samples for biochemical tests (amylase, lipase, malondialdehyde (MDA) and catalase (CAT)) and tissue samples for histopathological and immunohistochemical examinations (caspase-3, insulin and glucagon) were collected. RESULTS: Comparing the control and HFCS groups, serum glucose (150.92 ± 39.77 and 236.50 ± 18.28, respectively, p < 0.05), amylase (2165.00 ± 150.76 and 3027.66 ± 729.19, respectively, p < 0.01), lipase (5.58 ± 2.22 and 11.51 ± 2.74, respectively, p < 0.01) and pancreatic tissue MDA (0.0167 ± 0.004 and 0.0193 ± 0.006, respectively, p < 0.05) levels were increased, whereas tissue CAT (0.0924 ± 0.029 and 0.0359 ± 0.023, respectively, p < 0.05) activity decreased in the HFCS group significantly. Histopathological examination revealed degenerative and necrotic changes in Langerhans islet cells and slight inflammatory cell infiltration in pancreatic tissue in the HFCS group. Immunohistochemically there was a significant decrease in insulin (2.85 ± 0.37 and 0.87 ± 0.64, respectively, p < 0.001) and glucagon (2.71 ± 0.48 and 1.00 ± 0.75, respectively, p < 0.001) secreting cell scores, whereas a greater increase in caspase-3 (0.14 ± 0.37 and 1.00 ± 0.75, respectively, p < 0.05) expression was seen in this group compared with the controls. In the ALA-treated group, all of these pathologic conditions were improved. CONCLUSIONS: This study indicated HFCS induced pancreatic lesions, but ALA had ameliorative effects.
Assuntos
Antioxidantes/farmacologia , Xarope de Milho Rico em Frutose/toxicidade , Pâncreas/efeitos dos fármacos , Ácido Tióctico/farmacologia , Animais , Antioxidantes/administração & dosagem , Feminino , Imuno-Histoquímica , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Ácido Tióctico/administração & dosagemRESUMO
OBJECTIVE: To determine the relationship between central adiposity parameters and autonomic nervous system (ANS) dysfunction. SUBJECTS AND METHODS: The study included 114 obese individuals without any cardiovascular risk factors. Weight (in kg), height (in m), and waist circumference (WC; in cm) were measured and body mass index was calculated. Echocardiographic examination was performed to measure left ventricular mass and epicardial fat thickness (EFT). All the participants underwent an exercise test and electrophysiological evaluation using electromyography. Heart rate recovery (HRR) at 1-5 min, R-R interval variation at rest and during hyperventilation, and sympathetic skin response were measured. Pearson's correlation analysis was used. Multiple linear regression analysis was used to identify the factors associated with autonomic dysfunction. RESULTS: The HRR at 1-5 min was negatively correlated with WC and age (WC-HRR1: r = -0.32; WC-HRR2: r = -0.31; WC-HRR3: r = -0.26; WC-HRR4: r = -0.23; WC-HRR5: r = -0.21; age-HRR2: r = -0.32; age-HRR3: r = -0.28; age-HRR4: r = -0.41; age-HRR5: r = -0.42). Age was the only independent predictor of reduced HRR at 1-5 min. In addition, WC predicted a reduced HRR at 3 min. There were no significant associations between central obesity and electrophysiological parameters. EFT was not associated with ANS dysfunction. CONCLUSION: In this study, central adiposity and aging were associated with ANS dysfunction in obese individuals. The WC could be a marker of ANS dysfunction in obese individuals without any cardiovascular risk factors. The HRR assessment at a later decay phase could be more valuable for evaluating ANS function than during early recovery.
Assuntos
Doenças do Sistema Nervoso Autônomo/epidemiologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Obesidade/epidemiologia , Obesidade/fisiopatologia , Circunferência da Cintura , Adolescente , Adulto , Fatores Etários , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Pesos e Medidas Corporais , Eletrocardiografia , Eletromiografia , Teste de Esforço , Feminino , Frequência Cardíaca/fisiologia , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: Obesity is well known to be linked to higher morbidity and mortality. Elevated plasma levels of free dehydroepiandrosterone (DHEA) are associated with reduced obesity and more limited accumulation of abdominal body fat. In contrast, the relationship between the DHEA sulfate ester (DHEAS) and adiposity is inconsistent and contradictory. METHODS: The aim of this study was to compare DHEAS levels in obese Turkish individuals, 37 men and 246 women. A variety of fatness, hormone, and blood parameters were measured. RESULTS: Statistically significant differences were found between male and female individuals with respect to weight, waist circumference, fat %, insulin, and DHEAS levels. CONCLUSIONS: We found that in the Turkish population, while a correlation between obesity parameters and DHEAS levels exists in both female and male individuals, DHEAS levels are significantly higher in obese male individuals than in obese female individuals.
Assuntos
Sulfato de Desidroepiandrosterona/sangue , Obesidade/sangue , Adolescente , Adulto , Idoso , Composição Corporal , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Turquia , Adulto JovemRESUMO
Background: Lipopolysaccharides (LPSs) are a component of certain types of bacteria and can induce an inflammatory response in the body, including in the pancreas. Cannabidiol (CBD), a nonpsychoactive compound found in cannabis, has been shown to have anti-inflammatory effects and may offer potential therapeutic benefits for conditions involving inflammation and damage. The aim of this study was to investigate any potential preventative effects of CBD on experimental LPS-induced pancreatic pathology in rats. Materials and Methods: Thirty-two rats were randomly divided into four groups as control, LPS (5 mg/kg, intraperitoneally [i.p.]), LPS+CBD, and CBD (5 mg/kg, i.p.) groups. Six hours after administering LPS, the rats were euthanized, and blood and pancreatic tissue samples were taken for biochemical, polymerase chain reaction (PCR), histopathological, and immunohistochemical examinations. Results: The results indicated that LPS decreased serum glucose levels and increased lipase levels. It also caused severe hyperemia, increased vacuolization in endocrine cells, edema, and slight inflammatory cell infiltrations at the histopathological examination. Insulin and amylin expressions decreased during immunohistochemical analyses. At the PCR analysis, Silent Information Regulator 2 homolog 1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha expressions decreased and tumor protein p53 expressions increased in the LPS group. CBD improved the biochemical, PCR, histopathological, and immunohistochemical results. Conclusions: The findings of the current investigation demonstrated that LPS damages both the endocrine and exocrine pancreas. However, CBD demonstrated marked ameliorative effects in the pancreas in LPS induced rat model pancreatitis.
RESUMO
The aim of this study was to investigate association between the frequencies of Growth Hormone receptor (d3GHR) gene polymorphisms and some clinical parameters of acromegalic patients. Total of 35 acromegalic patients were enrolled to study. The d3GHR polymorphism was identified by using polymerase chain reaction from peripheral blood samples. The levels of systolic and diastolic blood pressure, BMI, fasting plasma glucose (FPG), Fasting insulin, HOMA-IR, IGF-I, GH, IGFBP3, triglyceride, HDL and LDL cholesterol concentrations were evaluated. The frequencies of d3GHR genotypes were found as follows; 5 (14.3%) subjects had d3/d3, 11 (31.4%) had d3/fl and 19 (54.3%) had fl/fl in patients. The prevalence of the d3 and fl alleles was 30 and 70%, respectively. Systolic blood pressure, fasting insulin and HOMA-IR was found significantly increased in homozygote d3GHR genotype group compared to d3/fl subjects (P < 0.05). In addition, BMI was observed significantly different among three genotypes (P = 0.007) and in the subjects with d3/d3 genotype, BMI was found significantly higher than d3/fl and fl/fl genotypes groups. As well as, no significant difference was found between the d3 and fl alleles group in terms of the clinical parameters except for BMI (P = 0.002). It can be said that the d3GHR gene polymorphism may affect BMI, systolic blood pressure and insulin regulation. At the same time we can say homozygote d3GHR genotype and d3 allele carriers may have more risk than other genotypes for high BMI.
Assuntos
Acromegalia/genética , Índice de Massa Corporal , Proteínas de Transporte/genética , Glucose/metabolismo , Receptores da Somatotropina/genética , Acromegalia/fisiopatologia , Adulto , Éxons , Feminino , Deleção de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
The effect of stress on the occurrence of diabetes mellitus (DM) is commonly reported in recent studies. Maternal stress may have a negative effect on the later life of offspring. However, most studies only investigated long-term intrauterine stress on behavioral, emotional, psychological, and immunological disorders of offspring. The relationship between maternal stress and DM occurrence in the later life period of offspring is not known. This rat model study aimed to evaluate the susceptibility of offspring to DM after exposure to intrauterine stress. The purpose of this study is to examine serum glucose levels of mothers and offspring exposed to maternal stress and to evaluate pancreatic tissues pathologically and immunohistochemically. Twelve, Wistar Albino female rats were equally divided into two groups: controls and maternal stress groups. Normal routine conditions were applied to the control group without any stress. The pregnant rats in the maternal stress group were exposed to chronic unpredictable stressors throughout the 21-day gestation. One female and one male offspring and mothers from each term delivery were randomly selected and euthanatized at the 35th day. During the necropsy, blood and pancreatic tissue samples were collected from both mothers and pups. High serum glucose levels from mothers and offspring in the maternal stress group and the control group were compared. Additionally, histopathological examinations assessed the increased cell degeneration in mother rats and offspring. Immunohistochemical examinations revealed decreased insulin, amylin, and insulin receptor expressions and slightly increased glucagon expression in Langerhans islet cells in the maternal stress group. These results indicated that maternal stress may be a predisposing factor for DM in both mothers and offspring in their later life periods.
Assuntos
Diabetes Mellitus , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Insulina/metabolismo , Masculino , Modelos Teóricos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos WistarRESUMO
We investigated the therapeutic potential of taxifolin for treatment of alveolar bone loss (ABL) in experimental periodontitis in diabetic rats. Diabetes mellitus (DM) was induced by streptozotocin. Rats were divided into six groups: untreated control; DM only (D) group; ligature only (P) group; DM + ligature (DP) group; DM + ligature + 5 mg/kg/day taxifolin (Taxi-5) group; DM + ligature + 10 mg/kg/day taxifolin (Taxi-10) group. Experimental periodontitis was induced by ligation of the first molar and allowed to progress for 30 days before performing cone-beam computed tomographic (CBCT), histomorphometric and immunohistochemical analyses of periodontal tissue destruction. ABL was assessed using CBCT. ABL was greatest in the P and DP groups. Decreased ABL was observed in the Taxi-5 and Taxi-10 groups. Bone morphogenic protein (BMP-2), osteocalcin (OCN), receptor activator of nuclear factor kappa-Β ligand (RANKL), alkaline phosphatase (ALP), type I collagen, B cell lymphoma-associated X (Bax), and B-cell lymphoma 2 (Bcl-2) levels were investigated using immunohistochemistry. The Taxi-5 and Taxi-10 groups exhibited decreased RANKL expression, but increased BMP-2, ALP, type I collagen and OCN levels compared to the P and DP groups. Bax activity was increased in the D, P and DP groups. Taxi-5 and Taxi-10 groups exhibited increased Bcl-2 activity. Our findings suggest that taxifolin can reduce apoptosis and improve alveolar bone formation in diabetic rats with periodontitis.
Assuntos
Diabetes Mellitus Experimental , Periodontite , Animais , Apoptose , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Osteogênese , Periodontite/metabolismo , Quercetina/análogos & derivados , RatosRESUMO
BACKGROUND: The effects of adipokines have been investigated in multiple sclerosis (MS) in the literature. Results are uncertain, and subgroups like adropin have not been previously studied. We primarily aimed to determine leptin and adropin levels in MS and their potential use as a biomarker. METHODS: This study was an experimental research. While 44 MS patients diagnosed according to McDonald criteria were included in the patient group, 40 people without MS diagnosis and risk factors took part in the control group. Demographic data, height, weight, body mass index, blood glucose, thyroid-stimulating hormone, alanine transaminase, aspartate transaminase, creatinine, low-density lipoprotein, leptin, adropin levels, presence of hypertension, diabetes mellitus, coronary artery disease were recorded. Expanded disability status scale and disease duration were also evaluated in the patient group. Our data were presented as meanâ±âstandard deviations. RESULTS: The mean blood leptin value of the patient group (6.12â±â5.34âng/mL) was significantly lower than the value of the control group (13.02â±â8.25âng/mL) (Pâ<â.001). The patient group had a mean adropin level of 504.12â±â311.17âng/mL, which was significantly lower than that of the control group (747.0â±â309.42âng/mL) (Pâ<â.001). Statistically insignificant differences were found between their body mass index, glucose, alanine transaminase, aspartate transaminase, thyroid-stimulating hormone, low-density lipoprotein levels (Pâ>â.001). CONCLUSION: This is the first study that has evaluated adropin levels in patients with MS. The relationship between MS and leptin levels is still unclear. Therefore, our study might be helpful to elucidate MS pathogenesis and provide supportive criteria for diagnosis.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/análise , Leptina/análise , Esclerose Múltipla/sangue , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Turquia/epidemiologiaRESUMO
OBJECTIVES: To describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. METHODS: Retrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. RESULTS: A total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. CONCLUSIONS: This is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).
Assuntos
Acromegalia/cirurgia , Biomarcadores/sangue , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/análise , Sistema de Registros/estatística & dados numéricos , Acromegalia/sangue , Acromegalia/epidemiologia , Acromegalia/patologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Turquia/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to examine pancreatic pathology and the prophylactic effects of pregabalin in lipopolysaccharide (LPS) induced sepsis model in aged rats. METHODS: Twenty-four female, one-year-old, Wistar Albino rats were assigned to three groups; Group I (control), Group II (study group: 5mg/kg LPS intraperitoneal, single dose) and Group III(treatment group: 5mg/kg LPS+30 mg/kg oral pregabalin one hour before LPS). Animals were sacrificed by exsanguination 6 hours after LPS administration. Blood and pancreatic tissue samples were collected for biochemical, pathological, and immunohistochemical analyses. RESULTS: LPS caused increases in serum amylase and lipase level but led to a reduction in glucose levels. Following histopathological analysis, numerous neutrophil leucocyte infiltrations were observed in vessels and pancreatic tissues. Increased caspase-3 expression was observed in both the endocrine and exocrine pancreas in the LPS group. Similarly, IL-6, caspase-3 (Cas-3), inducible nitric oxide synthase (iNOS), granulocyte colony-stimulating factor (G-CSF) and serum amyloid-A (SAA) expressions were increased by LPS. Pregabalin improved biochemical, histopathological, and immunohistochemical findings. CONCLUSION: This study showed that LPS causes pathological findings in the pancreas, but pregabalin has ameliorative effects in aged rats with sepsis. Cas-3, IL-6, iNOS, G-CSF, and SAA all play pivotal roles in the pathogenesis of LPS-induced pancreatic damage.
Assuntos
Anti-Inflamatórios/farmacologia , Lipopolissacarídeos , Pâncreas/efeitos dos fármacos , Pancreatite/prevenção & controle , Pregabalina/farmacologia , Animais , Caspase 3/metabolismo , Citoproteção , Modelos Animais de Doenças , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite/sangue , Pancreatite/induzido quimicamente , Pancreatite/patologia , Ratos Wistar , Proteína Amiloide A Sérica/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Diabetes mellitus become an epidemic problem throughout the world. Relation of the diabetes with diet is known. Some evidence is reported about mother died and risk of diabetes in babies during the life related with gestational diabetes. This study was conducted to examine the effects of the exposure of high-dose sucrose to rats and pups during pregnancy and lactation. METHODS: The mother rats were categorized into four groups, during pregnancy and until the offspring were 1-month-old, as follows: Group 1, provided with normal drinking water; Group 2, provided with water containing 10%; Group 3, 20%; and Group 4, 30% table sugar. During the study, the weights and daily fluid consumption of the animals were recorded. At the end of the study, the changes in blood, urine, and pancreatic tissues of the rats were examined. RESULTS: The pups in the groups supplemented with sugar had more weight gain than those of the control group. Although serum glucose levels of mothers and young rats in the groups fed with sugar-containing water did not reach the diabetic limits, it was observed that these animals had statistically significantly higher blood glucose levels than those in the control group. Insulin levels were also similarly increased by an increase in the amount of sugar. Immunohistochemical studies on the mother rats showed that insulin secreted cell numbers and insulin receptors significantly decreased in some pancreatic islets in the groups supplemented with sugar. Glucagon immunoreactivity examination showed that the number of glucagon-expressing cells decreased in the rat groups supplemented with sugar. Similar and more severe findings were observed in the offspring. CONCLUSION: This study has experimentally demonstrated that high daily intake of sugar in healthy pregnancies causes adverse effects on the mother and offspring.
Assuntos
Diabetes Gestacional/metabolismo , Glucose/toxicidade , Hiperglicemia/metabolismo , Pâncreas/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Animais Recém-Nascidos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/patologia , Feminino , Glucagon/metabolismo , Glucose/administração & dosagem , Hiperglicemia/induzido quimicamente , Hiperglicemia/patologia , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , RatosRESUMO
BACKGROUND: Acromegaly is a rare and serious syndrome that is commonly associated with pituitary neoplasms. Thyroid multinodular disease is a common finding in acromegaly. Leptin is a polypeptide hormone, and studies have shown that it can increase cell proliferation and inhibit apoptosis. OBJECTIVES: The aim of the study was to determine the relationship of serum leptin levels with certain blood parameters and determine if growth hormone receptor (GHR)-d3/fl gene polymorphism is associated with thyroid nodules in acromegalic patients. MATERIAL AND METHODS: A total of 24 acromegalic patients with or without thyroid nodules were included in the study. Gene polymorphisms and blood parameters were examined. RESULTS: A marked increase was observed in serum leptin concentration in acromegalic patients with thyroid nodules compared to patients without them (p < 0.05). GH levels were lower in patients without nodules than in patients with nodules (p < 0.05). Blood glucose levels were higher in patients with nodules compared to those without them (p < 0.05), and the presence of thyroid nodules was associated with decreased blood low-density lipoprotein (LDL) levels compared to patients without nodules (p < 0.05). A significant relationship was observed between growth hormone receptor (GHR)-d3/fl gene polymorphism and leptin levels in acromegalic patients with thyroid nodules (p < 0.001). CONCLUSIONS: These data from acromegalic patients indicate that thyroid nodules are associated with increased serum leptin, GH and blood glucose levels and with decreased LDL levels. GHR-d3/fl gene polymorphism status was strongly related to higher leptin levels.
Assuntos
Acromegalia/genética , Leptina/sangue , Polimorfismo Genético , Receptores da Somatotropina/genética , Nódulo da Glândula Tireoide/complicações , Acromegalia/sangue , Acromegalia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Éxons/genética , Feminino , Deleção de Genes , Frequência do Gene , Genótipo , Hormônio do Crescimento Humano/sangue , Humanos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
In this study, the diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated, and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into three different study and control groups according to the duration of the OTA administration. The rats received 45 µg OTA daily in their feed for 6, 9 and 24 weeks, respectively. Three control groups were also used for the same time periods. Blood and pancreatic tissue samples were collected during the necropsy at the end of the 6, 9 and 24 weeks. The plasma values of insulin, glucagon and glucose were determined for the study and control groups. Pancreatic lesions were evaluated via histopathological examination and insulin and glucagon expression in these lesions was subsequently determined using immunohistochemical methods. Statistically significant decreases in insulin levels were observed, in contrast to increases in blood glucagon and glucose levels. Histopathological examinations revealed slight to moderate degeneration in Langerhans islet cells in all OTA-treated groups. Immunohistochemistry of pancreatic tissue revealed decreased insulin and increased glucagon expression. This study demonstrated that OTA may cause pancreatic damage in the Langerhans islet and predispose rats to DM.
Assuntos
Ocratoxinas/toxicidade , Pâncreas/efeitos dos fármacos , Animais , Glicemia/análise , Diabetes Mellitus , Feminino , Glucagon/sangue , Glucagon/metabolismo , Insulina/sangue , Insulina/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Ratos WistarRESUMO
In recent years, pancreatic pathologies have become common problems and their etiology and pathogenesis are generally unknown. Studies have shown that smoking may increase the risk of pancreatic disorders but very scant knowledge is available about the pathogenesis of cigarette induced pancreatic pathology. This study aimed to evaluate the oxidative stress status, biochemical, pathological and immunohistochemical findings of rats exposed to cigarette smoke, pathogenesis of smoking related pancreatic damage and usability of Alpha Lipoic Acid (ALA) for amelioration of cigarette smoking induced harmful effects on rat pancreas. Twenty eight female, Sprague Dawley rats were randomly distributed into three groups. The sham group (S) (n = 8), rats were given 0.1 ml of physiological serum by oral gavage for 8 weeks. The cigarette smoke exposed group (CSE) (n = 10), rats were exposed to successive periods of cigarette smoke for 2 hours per day per 8 weeks and given 0.1 ml of physiological serum orally during the study. The cigarette smoke exposed and ALA treated group (CSE + ALA) (n = 10), animals were exposed to cigarette smoke (2 hours per day per 8 weeks) and simultaneously treated with 100 mg per kg per day ALA orally during the study. At the end of the study, the serum samples were collected for insulin, glucagon, glucose and amylase analyses. Tissue samples were collected for biochemical, histopathological and immunohistochemical examinations. Total oxidant status (TOS), total antioxidant status (TAS) levels and oxidative stress index (OSI) were evaluated in the pancreas samples. Immunohistochemical analyses of insulin, glucagon, calcitonin gene related protein (CGRP), active caspase-3, hypoxia inducible factor-1 (Hif-1), Hif-2 and tumor necrosis factor (TNF-α) expressions of pancreas were examined. Cigarette smoke caused statistically significant increase in serum amylase and glucose but decreased insulin levels indicating both endocrine and exocrine cell damage. There were no statistically significant differences in serum glucagon levels between the groups. Histopathological examination of the pancreas exhibited generally normal tissue architecture but slightly degenerative and apoptotic cells were noticed both in the endocrine and exocrine part of the pancreas in the CSE group. Immunohistochemical analyses revealed marked increase in active caspase-3, Hif-1 and Hif-2, CGRP and TNF-α expressions with a slight increase in glucagon immunoreactivity in cells while a marked decrease was observed in insulin expression in some Langerhans islets in the CSE group. ALA ameliorated biochemical and pathological findings in the CSE + ALA group. These findings clearly demonstrated that cigarette smoke can cause damage in both endocrine and exocrine cells in rat pancreas and ALA has an ameliorative effect of cigarette induced lesions.
RESUMO
OBJECTIVES: Diabetes mellitus (DM) is a global epidemic with increasing prevalence. The disease is chronic in nature, and patients must use antidiabetic drugs or insulin during their lifespan. Because of the difficulty of using injectable insulin preparations, patients and practitioners prefer to use oral antidiabetic drugs for prophylaxis and treatment. There are, however, numerous adverse effects of antidiabetic drugs and rapidly increasing attention is being paid to new nutraceutical drugs with fewer adverse effects. The purpose of this study was to evaluate the effects of caffeine and lycopene on streptozotocin (STZ)-induced DM in rats. METHODS: Caffeine and lycopene were administered to the study groups by oral gavages for 1 month whereafter experimental diabetes was induced in 90 rats in 6 groups. RESULTS: There were no pathological effects of lycopene and caffeine on the pancreas. Marked vacuolization and degeneration were observed in STZ-treated groups. Caffeine and lycopene decreased the pathological findings and lowered the blood and urine glucose levels in the rats with STZ-induced DM, whereas these compounds increased serum insulin levels. CONCLUSIONS: This study showed that caffeine and lycopene provided protective effects against experimentally induced DM. The protective effects of lycopene were observed to be much greater than those of caffeine.
Assuntos
Cafeína/farmacologia , Carotenoides/farmacologia , Diabetes Mellitus Experimental/prevenção & controle , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Glicemia/análise , Cafeína/administração & dosagem , Carotenoides/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/urina , Glucagon/análise , Glicosúria/urina , Imuno-Histoquímica , Insulina/análise , Insulina/sangue , Licopeno , Pâncreas/metabolismo , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The aim of this study was to investigate the protective effects of aspirin (AS) and vitamin C (VC) against cardiac damage induced by chronic corn syrup (CS) consumption via a mechanism involving sirtuin-1 (ST-1), hypoxia-inducible factor-1α (HIF-1α), and the caspase-3 pathway in rats. METHODS: Forty male Sprague-Dawley rats (14-16 weeks) that weighed 250-300 g were randomly distributed into 5 groups, each containing 8 rats: control group, CS+AS group, CS+VC group, CS+AS+VC group, and CS group. AS (10 mg/kg/day) and VC (200 mg/kg/day) were orally given to the rats. F30 (30% fructose syrup solution) was given to the rats in drinking water for 6 weeks. The rats were sacrificed by exsanguination 24 h after the last administration. Blood samples and tissue were collected for biochemical, histopathological, and immunohistochemical examinations. Non-parametric Kruskal-Wallis test and Mann-Whitney U test used for the parameters without normal distribution and ANOVA and post-hoc LSD tests were used for parameters with a normal distribution to compare groups. RESULTS: Uric acid, creatine kinase (CKMB), and lactate dehydrogenase (LDH) levels were increased in the CS group compared with the control group (1.45±0.39 and p=0.011; 3225.64±598.25 and p=0.004; 3906.83±1064.22 and p=0.002, respectively) and decreased in all the treatment groups. In addition, increased levels of MDA and decreased activity of CAT in the CS group (0.172±0.03 and p=0.000; 0.070±0.005 and p=0.007, respectively) were reversed with AS and VC therapy. A decrease in ST-1 activity and increases in caspase-3 and HIF-1 activities corrected by VC and AS therapy were observed. CONCLUSION: AS and VC, which display antioxidant and antiapoptotic activities, ameliorated cardiac damage induced by chronic fructose consumption by increasing the levels of ST-1 and decreasing the levels of HIF-1α and caspase-3.
Assuntos
Ácido Ascórbico/farmacologia , Aspirina/farmacologia , Frutose/efeitos adversos , Traumatismos Cardíacos/induzido quimicamente , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Sirtuína 1/fisiologia , Animais , Antipaína , Açúcares da Dieta/efeitos adversos , Coração/efeitos dos fármacos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Zea maysRESUMO
BACKGROUND: Acromegaly is associated with increased morbidity and mortality related to cardiovascular diseases. Leptin (LEP) and Leptin Receptor (LEPR) gene polymorphisms can increase cardiovascular risks. The aim of this study was to investigate association between the frequencies of LEP and LEPR gene polymorphisms and subclinical atherosclerosis in acromegalic patients. METHODS: Forty-four acromegalic patients and 30 controls were admitted to study. The polymorphisms were identified by using polymerase chain reaction from peripheral blood samples. The levels of systolic and diastolic blood pressure, BMI, fasting plasma glucose, fasting insulin, IGF-I, GH, IGFBP3, leptin, triglyceride, carotid Intima Media Thickness (cIMT) and HDL and LDL cholesterol concentrations were evaluated. RESULTS: There was statistically significant difference between the LEPR genotypes of acromegalic patients (GG 11.4%, GA 52.3%, and AA 36.4%) and controls (GG 33.3%, GA 50%, and AA 16.7%) although their LEP genotype distribution was similar. In addition, the prevalence of the LEPR gene G and A alleles was significantly different between patients and controls. No significant difference was found among the G(-2548) A leptin genotypes of groups in terms of the clinical parameters. cIMT significantly increased homozygote LEPR GG genotype group compared to AA subjects in patients. But the other parameters were not different between LEPR genotypes groups of patients and controls. CONCLUSION: It can be said that the LEPR gene polymorphism may affect cIMT in patients. The reason is that LEPR GG genotype carriers may have more risk than other genotypes in the development of subclinical atherosclerosis in acromegaly.