RESUMO
Type 2 diabetes mellitus (T2DM) is a major global public health concern, prompting the ongoing search for new treatment options. Medicinal plants have emerged as one such alternative. Our objective was to evaluate the antidiabetic effect of an extract from the leaves of Passiflora ligularis (P. ligularis). For this purpose, T2DM was first induced in mice using a high-fat diet and low doses of streptozotocin. Subsequently, an aqueous extract or an ethanolic extract of P. ligularis leaves was administered for 21 days. The following relevant results were found: fasting blood glucose levels were reduced by up to 41%, and by 29% after an oral glucose overload. The homeostasis model assessment of insulin resistance (HOMA-IR) was reduced by 59%. Histopathologically, better preservation of pancreatic tissue was observed. Regarding oxidative stress parameters, there was an increase of up to 48% in superoxide dismutase (SOD), an increase in catalase (CAT) activity by 35% to 80%, and a decrease in lipid peroxidation (MDA) by 35% to 80% in the liver, kidney, or pancreas. Lastly, regarding the lipid profile, triglycerides (TG) were reduced by up to 30%, total cholesterol (TC) by 35%, and low-density lipoproteins (LDL) by up to 32%, while treatments increased high-density lipoproteins (HDL) by up to 35%. With all the above, we can conclude that P. ligularis leaves showed antihyperglycemic, hypolipidemic, and antioxidant effects, making this species promising for the treatment of T2DM.
Assuntos
Glicemia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Dieta Hiperlipídica , Hipoglicemiantes , Passiflora , Extratos Vegetais , Folhas de Planta , Animais , Folhas de Planta/química , Diabetes Mellitus Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Hipoglicemiantes/farmacologia , Dieta Hiperlipídica/efeitos adversos , Passiflora/química , Camundongos , Masculino , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Estreptozocina , Resistência à Insulina , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/metabolismo , Antioxidantes/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lipídeos/sangue , FitoterapiaRESUMO
The increasing global prevalence and associated comorbidities need innovative approaches for type 2 diabetes mellitus (T2DM) prevention and treatment. Genetics contributes significantly to T2DM susceptibility, and genetic counseling is significant in detecting and informing people about the diabetic risk. T2DM is also intricately linked to overnutrition and obesity, and nutritional advising is beneficial to mitigate diabetic evolution. However, manipulating pancreatic cell plasticity and transdifferentiation could help beta cell regeneration and glucose homeostasis, effectively contributing to the antidiabetic fight. Targeted modulation of transcription factors is highlighted for their roles in various aspects of pancreatic cell differentiation and function, inducing non-beta cells' conversion into functional beta cells (responsive to glucose). In addition, pharmacological interventions targeting specific receptors and pathways might facilitate cell transdifferentiation aiming to maintain or increase beta cell mass and function. However, the mechanisms underlying cellular reprogramming are not yet well understood. The present review highlights the primary transcriptional factors in the endocrine pancreas, focusing on transdifferentiation as a primary mechanism. Therefore, islet cell reprogramming, converting one cell type to another and transforming non-beta cells into insulin-producing cells, depends, among others, on transcription factors. It is a promising fact that new transcription factors are discovered every day, and their actions on pancreatic islet cells are revealed. Exploring these pathways associated with pancreatic development and islet endocrine cell differentiation could unravel the molecular intricacies underlying transdifferentiation processes, exploring novel therapeutic strategies to treat diabetes. The medical use of this biotechnology is expected to be achievable within a short time.
Assuntos
Transdiferenciação Celular , Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Humanos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/citologia , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/metabolismo , Animais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Diferenciação Celular , Pâncreas/metabolismo , Pâncreas/patologiaRESUMO
BACKGROUND: Acute pancreatitis is an inflammation of the pancreatic glandular parenchyma that causes injury with or without the destruction of pancreatic acini. Clinical and experimental evidence suggest that certain systemic proinflammatory mediators may be responsible for initiating the fundamental mechanisms involved in microglial reactivity. Here, we investigated the possible repercussions of acute pancreatitis (AP) on the production of inflammatory mediators in the brain parenchyma focusing on microglial activation in the hippocampus. METHODS: The acute pancreatic injury in rats was induced by a pancreas ligation surgical procedure (PLSP) on the splenic lobe, which corresponds to approximately 10% of total mass of the pancreas. Blood samples were collected via intracardiac puncture for the measurement of serum amylase. After euthanasia, frozen or paraffin-embedded brains and pancreas were analyzed using qRT-PCR or immunohistochemistry, respectively. RESULTS: Immunohistochemistry assays showed a large number of Iba1 and PU.1-positive cells in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus of the PLSP group. TNF-α mRNA expression was significantly higher in the brain from PLSP group. NLRP3 inflammasome expression was found to be significantly increased in the pancreas and brain of rats of the PLSP group. High levels of BNDF mRNA were found in the rat brain of PLSP group. In contrast, NGF mRNA levels were significantly higher in the control group versus PLSP group. CONCLUSION: Our findings suggest that AP has the potential to induce morphological changes in microglia consistent with an activated phenotype.
Assuntos
Pancreatite , Ratos , Animais , Pancreatite/metabolismo , Microglia/metabolismo , Doença Aguda , Hipocampo/metabolismo , Pâncreas/metabolismo , RNA Mensageiro/metabolismoRESUMO
The world is experiencing reflections of the intersection of two pandemics: Obesity and coronavirus disease 2019. The prevalence of obesity has tripled since 1975 worldwide, representing substantial public health costs due to its comorbidities. The adipose tissue is the initial site of obesity impairments. During excessive energy intake, it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs. The pancreas is one of the organs most affected by obesity. Once lipotoxicity becomes chronic, there is an increase in insulin secretion by pancreatic beta cells, a surrogate for type 2 diabetes mellitus (T2DM). These alterations threaten the survival of the pancreatic islets, which tend to become dysfunctional, reaching exhaustion in the long term. As for the liver, lipotoxicity favors lipogenesis and impairs beta-oxidation, resulting in hepatic steatosis. This silent disease affects around 30% of the worldwide population and can evolve into end-stage liver disease. Although therapy for hepatic steatosis remains to be defined, peroxisome proliferator-activated receptors (PPARs) activation copes with T2DM management. Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways, leading to insulin resistance relief, improved thermogenesis, and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation. This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases, focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.
Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Resistência à Insulina , Doenças Metabólicas , Humanos , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Resistência à Insulina/fisiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , COVID-19/metabolismo , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Pâncreas/metabolismo , Fígado Gorduroso/metabolismoRESUMO
OBJECTIVE: We evaluated the effects of eugenol on histological, enzymatic, and oxidative parameters in the pancreas, parotid, submandibular, and sublingual glands of healthy male rats. DESIGN: Twenty-four adult Wistar rats were assigned into four groups (n = 6/group). Control rats received 2% Tween-20 (eugenol vehicle), whereas the other animals received 10, 20, and 40 mg kg-1 eugenol through gavage daily for 60 d. Major salivary and pancreatic glands were weighed and preserved fixed for microscopic analysis and frozen for in vitro assays. RESULTS: Eugenol did not alter glands' weight and serum amylase activity regardless of the concentration. The highest dose of eugenol caused an increase in pancreatic amylase activity and a reduction of lipase activity from serum and pancreas. Eugenol at 40 mg kg-1 diminished the activity of SOD and FRAP in the submandibular gland and CAT and FRAP in the sublingual gland. However, it did not exert any effect on GST regardless of the gland. Additionally, 40 mg kg-1 eugenol increased MDA levels in pancreatic, parotid, and submandibular glands and NO levels in the sublingual. The concentrations of eugenol induced distinct responses in the glands regarding the activity of Na+/K+, Mg2+, and total ATPase activity. They also affected histomorphometrical and histochemistrical parameters in the submandibular gland only. CONCLUSIONS: Results indicated that 40 mg kg-1 eugenol altered most of the biochemical and oxidatived parameters of digestive glands. Only submandibular glands presented histological changes after eugenol exposure suggesting potential implications for its function.
Assuntos
Eugenol , Glândulas Salivares , Ratos , Masculino , Animais , Ratos Wistar , Eugenol/farmacologia , Eugenol/metabolismo , Glândulas Salivares/metabolismo , Glândula Parótida/metabolismo , Glândula Submandibular/metabolismo , Glândula Sublingual , Pâncreas/metabolismo , Amilases/metabolismo , Estresse OxidativoRESUMO
AIMS: Obesity, aging, and physical training are factors influencing pancreatic functional and morphological parameters. Aiming to clarify the impact of the interaction of these factors, we analyzed the effect of therapeutic or lifelong physical training on body adiposity and pancreatic functional and morphological parameters of aged and obese rats. METHODS: 24 male Wistar rats were (initial age = 4 months and final age = 14 months) randomly divided into three aged and obese experimental groups (n = 8/group): untrained, therapeutic trained, and lifelong trained. Body adiposity, plasmatic concentration and pancreatic immunostaining of insulin, markers of tissue inflammation, lipid peroxidation, activity and immunostaining of antioxidant enzymes, and parameters of pancreatic morphology were evaluated. RESULTS: Lifelong physical training improved the body adiposity, plasmatic insulin concentration, and macrophage immunostaining in the pancreas. The animals submitted to therapeutic and lifelong training showed an increase in the density of the pancreatic islets; lower insulin, Nuclear Factor Kappa B (NF-κB), and Transforming Growth Factor beta (TGF-ß) immunostaining in the pancreatic parenchyma, as well as lower pancreatic tissue lipid peroxidation, lower fibrosis area, increased catalase and glutathione peroxidase (GPx) activity and increased heme oxygenase-1 (HO-1) immunostaining, with the greatest effect in the lifelong training group. CONCLUSION: Lifelong training promoted greater beneficial effects on the pancreatic functional and morphological parameters of aged and obese animals compared to therapeutic exercise.
Assuntos
Obesidade , Condicionamento Físico Animal , Ratos , Masculino , Animais , Ratos Wistar , Obesidade/metabolismo , Envelhecimento , Pâncreas/metabolismo , Insulina/metabolismo , Modelos Animais , Antioxidantes/farmacologia , Estresse OxidativoRESUMO
Alcohol-induced pancreas damage remains as one of the main risk factors for pancreatitis development. This disorder is poorly understood, particularly the effect of acetaldehyde, the primary alcohol metabolite, in the endocrine pancreas. Hepatocyte growth factor (HGF) is a protective protein in many tissues, displaying antioxidant, antiapoptotic, and proliferative responses. In the present work, we were focused on characterizing the response induced by HGF and its protective mechanism in the RINm5F pancreatic cell line treated with ethanol and acetaldehyde. RINm5F cells were treated with ethanol or acetaldehyde for 12 h in the presence or not of HGF (50 ng/ml). Cells under HGF treatment decreased the content of reactive oxygen species and lipid peroxidation induced by both toxics, improving cell viability. This effect was correlated to an improvement in insulin expression impaired by ethanol and acetaldehyde. Using a specific inhibitor of Erk1/2 abrogated the effects elicited by the growth factor. In conclusion, the work provides mechanistic evidence of the HGF-induced-protective response to the alcohol-induced damage in the main cellular component of the endocrine pancreas.
Assuntos
Acetaldeído , Etanol , Acetaldeído/toxicidade , Acetaldeído/metabolismo , Linhagem Celular , Etanol/toxicidade , Fator de Crescimento de Hepatócito , Pâncreas/metabolismo , Sistema de Sinalização das MAP QuinasesRESUMO
During lactation, the maternal physiology adapts to bear the nutritional requirements of the offspring. The exocrine and endocrine pancreas are central to nutrient handling, promoting digestion and metabolism. In concert with prolactin, insulin is a determinant factor for milk synthesis. The investigation of the pancreas during lactation has been scattered over several periods. The investigations that laid the foundation of lactating pancreatic physiology and glucose homeostasis were conducted in the decades of 1970-1980. With the development of molecular biology, newer studies have revealed the molecular mechanisms involved in the endocrine pancreas during breastfeeding. There has been a surge of information recently about unexpected changes in the pancreas at the end of the lactation period and after weaning. In this review, we aim to gather information on the changes in the pancreas and glucose homeostasis during and after lactation and discuss the outcomes derived from the current discoveries.
Assuntos
Lactação , Pâncreas , Feminino , Humanos , Lactação/metabolismo , Pâncreas/metabolismo , Insulina/metabolismo , Glucose/metabolismo , HomeostaseRESUMO
This study aimed to investigate the impact of short-time hypothyroidism on the expression of aromatase, estrogen receptors (ERα, ß), and GPR30 in the pancreas of female rabbits. The formation of new islets and the expression of insulin, GLUT4, and lactate dehydrogenase (LDH) were also analyzed. This purpose is based on actions that thyroid hormones and estrogens have on ß-cells differentiation, acinar cell function, and insulin secretion. Twelve Chinchilla-breed adult virgin female rabbits were divided into control (n = 6) and hypothyroid (n = 6; methimazole 10 mg/kg for 30 days) groups. In the complete pancreas, expressions of aromatase and estrogen receptors, as well as proinsulin, GLUT4, and LDH were determined by western blot. Characteristics of islets were measured in slices of the pancreas with immunohistochemistry for insulin. Islet and acinar cells express aromatase, ERα, ERß, and GPR30. Hypothyroidism increased the expression of ERα and diminished that for aromatase, ERß, and GPR30 in the pancreas. It also promoted a high number of extra small islets (new islets) and increased the expression of proinsulin and GLUT4 in the pancreas. Our results show that actions of thyroid hormones and estrogens on ß-cells neogenesis, acinar cell function, and synthesis and secretion of insulin are linked. Thus, the effects of hypothyroidism on the pancreas could include summatory actions of thyroid hormones plus estrogens. Our findings indicate the importance of monitoring estrogen levels and actions on the pancreas of hypothyroid women, particularly when serum estrogen concentrations are affected such as menopausal, pregnant, and those with contraceptive use.
Assuntos
Hipotireoidismo , Receptores de Estrogênio , Animais , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Estrogênios/farmacologia , Feminino , Humanos , Pâncreas/metabolismo , Gravidez , Coelhos , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
BACKGROUND: Aerobic glycolysis has a pivotal role in the carcinogenic process. The current understanding of the functional role and mechanism of UCHL3-related aerobic glycolysis in pancreatic cancer is far from comprehensive, therefore requires an in-depth analysis on this aspect. METHODS: In the present research, the expressions of ubiquitin carboxyl-terminal hydrolase L3 (UCHL3), lactate dehydrogenase A (LDHA) and Forkhead box protein M1 (FOXM1) were detected by qRT-PCR, Western blot and immunohistochemistry. The effects of UCHL3 knockdown or overexpression on pancreatic cancer cells were examined by determining cell viability and colony formation. Aerobic glycolysis was assessed according to glucose uptake, lactic acid production, and lactate dehydrogenase (LDH) activity. Dual-luciferase reporter assay was performed to detect LDHA promoter activity. RESULTS: The results showed that UCHL3 expression was significantly increased in the pancreatic cancer tissues and cells, and that knocking down UCHL3 noticeably inhibited cell viability and aerobic glycolysis. Further investigations revealed that LDHA expression was promoted by UCHL3 and could be reduced by shFOXM1, and that low-expressed LDHA partly reversed the inhibition of aerobic glycolysis induced by overexpressed UCHL3. CONCLUSIONS: To conclude, this study demonstrates that UCHL3 plays a carcinogenic role by promoting aerobic glycolysis in pancreatic cancer, suggesting that UCHL3 may be a potential diagnostic and therapeutic target for the treatment of cancer.