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1.
An Acad Bras Cienc ; 93(suppl 3): e20201351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468491

RESUMO

Obesity is a major risk factor for type 2 diabetes mellitus development and is characterized by an abnormal expansion of adipose tissue and low-grade chronic inflammation that contribute to insulin resistance. Although there are multiple treatments, most therapies can produce undesirable side effects and therefore, new and effective treatments with fewer side effects are necessary. Previously, we demonstrated that a natural extract from the leaves of Eucalyptus tereticornis (OBE100) has anti-inflammatory, hypoglycemic and hypolipidemic activities. The major compounds identified in OBE100 were three pentacyclic triterpenoids, ursolic acid, oleanolic acid, and ursolic acid lactone. Triterpenoids have shown multiples biological activities. This current study compared the biological effect produced by OBE100 with five different reconstituted mixtures of these triterpenoids. Different cell lines were used to evaluate cytotoxicity, reactive oxygen species production, inflammatory cytokine expression, glucose uptake induction, leptin and adiponectin expression, and lipid accumulation. OBE100 treatment was the most efficacious and none of the formulated triterpenoid mixtures significantly improved on this. Moreover, OBE100 was less toxic and reduced reactive oxygen species production. Our study showed that the proven beneficial properties of triterpenoids may be enhanced due to the interaction with minor secondary metabolites present in the natural extract improving their anti-inflammatory properties.


Assuntos
Diabetes Mellitus Tipo 2 , Eucalyptus , Resistência à Insulina , Triterpenos , Extratos Vegetais/farmacologia , Triterpenos/farmacologia
2.
Braz J Biol ; 83: e250179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34524376

RESUMO

Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.


Assuntos
Diabetes Mellitus , Resistência à Insulina , Glucose , Quinase 3 da Glicogênio Sintase , Homeostase , Humanos
3.
Georgian Med News ; (316-317): 135-141, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34511460

RESUMO

The article discusses modern views on the metabolic characteristics of adipose tissue in patients with non-alcoholic fatty liver disease (NAFLD). An association has been shown between NAFLD and metabolic risk factors such as dyslipidemia, hyperglycemia, and visceral obesity. The analysis of modern literature on adipose tissue as an endocrine organ is carried out. The recently revealed physiological and pathophysiological properties of adipokines are discussed. It has been documented that adiponectin counteracts the effect of angiotensin II on endothelial cells and prevents their apoptosis by increasing the association between eNOS and heat shock protein. Adiponectin can function as a negative regulator of angiogenesis. It inhibits the proliferation and migration of endothelial cells and markedly inhibits the growth of new blood vessels. The ratio of adiponectin to leptin is a biomarker of adipose tissue dysfunction and correlates better and more accurately with insulin resistance than adiponectin or leptin. The researchers concluded that fatty tissue dysfunction caused by low adiponectin levels may contribute to oxidative stress and inflammation. Medications aimed at synthesizing adiponectin will be useful in the treatment of NAFLD, obesity, diabetes, and cardiovascular disease.


Assuntos
Adiponectina/metabolismo , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Tecido Adiposo , Células Endoteliais , Humanos , Leptina
4.
Zhonghua Gan Zang Bing Za Zhi ; 29(8): 807-811, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34517466

RESUMO

Non-alcoholic fatty liver disease has now become a common hepatic metabolic disease, but there is no universally approved therapeutic drug on the market, so there is an urgent need to explore relevant therapeutic drugs. Several studies have shown that the thyroid hormone receptor ß, which is specifically expressed in the liver, plays an important role in lipid metabolism. T3 analogs and thyroid hormone receptor ß-specific agonists have been developed for thyroid hormone receptor ß. Many studies have shown that it can inhibit hepatic triglyceride synthesis, increase hepatic cholesterol clearance, reduce lipid deposition, and at the same time partly increase insulin sensitivity, promote glucose metabolism, and improve inflammation. Therefore, it has become a therapeutic drug with great potential for the treatment of non-alcoholic fatty liver disease. Herein, the mechanism, clinical research and drug development status are reviewed in order to provide new ideas for targeted therapy of non-alcoholic fatty liver disease with thyroid hormone receptor ß.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Receptores beta dos Hormônios Tireóideos/genética
5.
Rev Assoc Med Bras (1992) ; 67(4): 590-596, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34495066

RESUMO

OBJECTIVE: Polycystic ovary syndrome can be divided into different subtypes, including insulin resistance and hyperandrogenism. The aim of this study was to investigate the relationship between serum asprosin levels and polycystic ovary syndrome subtypes. METHODS: A total of 93 women with polycystic ovary syndrome and 77 healthy women as controls were selected for this study. The clinical and laboratory data were compared between the Polycystic ovary syndrome group and the control group. The Polycystic ovary syndrome group was further divided into subgroups: (1) women with or without hyperandrogenism (polycystic ovary syndrome hyperandrogenism and Polycystic ovary syndrome none-hyperandrogenism, respectively) and (2) women with or without insulin resistance (polycystic ovary syndrome insulin resistance and Polycystic ovary syndrome none-insulin resistance, respectively). Serum asprosin was measured by using enenzyme-linked immunosorbent assay. RESULTS: Serum asprosin levels showed no significant difference between the polycystic ovary syndrome and control groups. However, it was significantly lower in the Polycystic ovary syndrome HA and insulin resistance groups compared with the respective Polycystic ovary syndrome none-hyperandrogenism and none-insulin resistance groups (p<0.05). In the Polycystic ovary syndrome group, serum asprosin was negatively correlated with body mass index, luteinizing hormone, testosterone, basal antral follicles, fasting insulin, homeostatic model assessment of insulin resistance, and triglycerides. After adjusting for body mass index, the correlations were not significant, and asprosin was only positively correlated with prolactin (prolactin; r=0.426, p<0.001). CONCLUSION: Our study shows that women with polycystic ovary syndrome hyperandrogenism or insulin resistance exhibit significantly lower serum asprosin levels compared with controls, and the lower asprosin level directly correlated with prolactin level.


Assuntos
Hiperandrogenismo , Resistência à Insulina , Hormônios Peptídicos , Síndrome do Ovário Policístico , Índice de Massa Corporal , Estudos Transversais , Feminino , Fibrilina-1 , Humanos , Insulina , Proteínas dos Microfilamentos , Fragmentos de Peptídeos , Síndrome do Ovário Policístico/complicações , Testosterona
6.
World J Gastroenterol ; 27(30): 4999-5018, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34497431

RESUMO

Metabolic associated fatty liver disease (MAFLD), formerly named "nonalcoholic fatty liver disease" occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity and mortality risk factor for major causes of death, such as cardiovascular, digestive, metabolic, neoplastic and neuro-degenerative diseases. However, progression of MAFLD and its associated systemic complications occur almost invariably in patients who experience the additional burden of intrahepatic and/or systemic inflammation, which acts as disease accelerator. Our review is focused on the new knowledge about the brain-gut-liver axis in the context of metabolic dysregulations associated with fatty liver, where insulin resistance has been assumed to play an important role. Special emphasis has been given to digital imaging studies and in particular to positron emission tomography, as it represents a unique opportunity for the noninvasive in vivo study of tissue metabolism. An exhaustive revision of targeted animal models is also provided in order to clarify what the available preclinical evidence suggests for the causal interactions between fatty liver, dysregulated endogenous glucose production and insulin resistance.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Encéfalo/diagnóstico por imagem , Glucose , Humanos , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem
7.
J Coll Physicians Surg Pak ; 31(9): 1015-1019, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34500513

RESUMO

OBJECTIVES: To determine the diagnostic accuracy of HOMA-IR, and QUICKI in diagnosing gestational diabetes mellitus (GDM) considering oral glucose tolerance test (OGTT) as gold standard. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi from September 2020 to February 2021. METHODOLOGY: Pregnant women with gestational age between 24 to 28 weeks, who reported to Endocrine Clinic of AFIP for OGTT, were included in the study. OGTT was performed by following ADA guidelines. Sample for fasting insulin was collected along with first fasting sample of OGTT. HOMA-IR and QUICKI were calculated simultaneously. Percentage was used for qualitative variable while median (IQR 25th-75th) was applied for quantitative variables. OGTT was used as gold standard for calculation of diagnostic accuracy of HOMA-IR and QUICKI. RESULTS: Out of 182 patients, 74 (40.6%) were found to have GDM on OGTT while 108 (59.4%) had normal OGTT. Women with GDM (n=74) had median values of fasting insulin 15.9 (IQR 11.2-17.77), HOMA-IR 3.5 (IQR 2.6-4.1) and QUICKI 0.31 (IQR 0.30-0.33) as compared to median values of fasting insulin 8.0 (IQR 5.9-10.3), HOMA-IR 1.60 (IQR 1.12-2.03) and QUICKI 0.35 (IQR 0.34-0.37) in patients (n=108) with normal response to OGTT, (p <0.001). On logistic regression analysis, there was a strong association of HOMA-IR and QUICKI with gestational diabetes mellitus (p <0.001, accuracy 84.6%). HOMA-IR at cutoff of ≤2 had 94.5% sensitivity, 72.2% specificity, 70% PPV, 95.1% NPV, and 81.31% overall diagnostic accuracy with 0.913 AUC. QUICKI at cutoff of 0.34 had 86.4% sensitivity, 83.3% specificity, 78.0% PPV, 90.0% NPV, and 84.61% overall diagnostic accuracy with 0.905 AUC. CONCLUSION: Fasting insulin and HOMA-IR were significantly higher while QUICKI was lower in patients of GDM as compared to non-GDM pregnant patients at 24 to 28 weeks of gestation. Being more convenient for patients, it has the potential to be used as screening tool for gestational diabetes. Key Words: HOMA IR, QUICKI, Gestational diabetes mellitus, Insulin.


Assuntos
Diabetes Gestacional , Resistência à Insulina , Glicemia , Estudos Transversais , Diabetes Gestacional/diagnóstico , Feminino , Teste de Tolerância a Glucose , Humanos , Lactente , Insulina , Gravidez
8.
BMC Pediatr ; 21(1): 373, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465300

RESUMO

BACKGROUND: Adverse metabolic outcomes later in life have been reported among children or young adults who were born as preterm infants. This study was conducted to examine the impact of very preterm/very low birth weight (VP/VLBW) birth and subsequent growth after hospital discharge on cardiometabolic outcomes such as insulin resistance, fasting glucose, and systolic and diastolic blood pressure (BP) among children at 6-8 years of age. METHODS: This retrospective cohort study included children aged 6-8 years and compared those who were born at < 32 weeks of gestation or weighing < 1,500 g at birth (n = 60) with those born at term (n = 110). Body size, fat mass, BP, glucose, insulin, leptin, adiponectin, and lipid profiles were measured. Weight-for-age z-score changes between discharge and early school-age period were also calculated, and factors associated with BP, fasting glucose, and insulin resistance were analyzed. RESULTS: Children who were born VP/VLBW had significantly lower fat masses, higher systolic BP and diastolic BP, and significantly higher values of fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), compared to children born at term. VP/VLBW was correlated with HOMA-IR and BPs after adjusting for various factors, including fat mass index and weight-for-age z-score changes. Weight-for-age z-score changes were associated with HOMA-IR, but not with BPs. CONCLUSIONS: Although children aged 6-8 years who were born VP/VLBW showed significantly lower weight and fat mass, they had significantly higher BPs, fasting glucose, HOMA-IR, and leptin levels. The associations of VP/VLBW with cardiometabolic factors were independent of fat mass and weight gain velocity.


Assuntos
Doenças Cardiovasculares , Resistência à Insulina , Nascimento Prematuro , Assistência ao Convalescente , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Alta do Paciente , Gravidez , Estudos Retrospectivos , Instituições Acadêmicas , Adulto Jovem
9.
Nat Commun ; 12(1): 5249, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475397

RESUMO

The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inactivation of orexin receptor type 1 in serotonin transporter-expressing cells of mice reduced insulin sensitivity in diet-induced obesity, mainly by decreasing glucose utilization in brown adipose tissue and skeletal muscle. Selective inactivation of orexin receptor type 2 improved glucose tolerance and insulin sensitivity in obese mice, mainly through a decrease in hepatic gluconeogenesis. Optogenetic activation of orexin neurons in lateral hypothalamus or orexinergic fibers innervating raphe pallidus impaired or improved glucose tolerance, respectively. Collectively, the present study assigns orexin signaling in serotonergic neurons critical, yet differential orexin receptor type 1- and 2-dependent functions in the regulation of systemic glucose homeostasis.


Assuntos
Glucose/metabolismo , Obesidade/metabolismo , Receptores de Orexina/metabolismo , Neurônios Serotoninérgicos/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Homeostase , Região Hipotalâmica Lateral/citologia , Região Hipotalâmica Lateral/metabolismo , Resistência à Insulina , Fígado/metabolismo , Camundongos , Fibras Nervosas/metabolismo , Obesidade/etiologia , Receptores de Orexina/genética , Orexinas/metabolismo , Núcleos da Rafe/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Transdução de Sinais
10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 354-358, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374253

RESUMO

Objective: To investigate the effects of NOD-like receptor protein 3 (NLRP3) signaling pathway on insulin resistance and the intervention of lactic acid receptor G protein-coupled receptor 81 (GPR81) agonist in nonalcoholic fatty liver disease (NAFLD) rats. Methods: Thirty SD male rats were randomly divided into three groups: control group, NAFLD group and GPR81 agonist group, with 10 rats in each group. Nonalcoholic fatty liver rat model was established by high fat diet. The rats in GPR81 agonist group were injected intraperitoneally with GPR81 specific agonist lactate (50 nmol/L) on the basis of nonalcoholic fatty liver model once a week, and the other two groups were injected with the same amount of normal saline for 12 weeks. The levels of liver biochemical indexes, fasting blood glucose, insulin and inflammatory factors in liver homogenate were measured, and the histopathological morphology of liver in each group was observed. The protein expressions of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), insulin receptor substrate 1 (IRS-1), Tyr465-IRS-1, Ser636-IRS-1, glucose transporter 4 (GLUT4) in liver tissue were detected by Western blot. The mRNA expression levels of NLRP3, ASC, caspase-1, IRS-1 and GLUT4 in liver tissue were detected by qRT-PCR. Results: Compared with the control group, the serum levels of triglyceride (TG), alanine aminotransfease (ALT), aspartate aminotransfease (AST), fasting plasma glucose (FPG), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) of NAFLD group were increased significantly (P< 0.05). The results of liver histopathology showed that in NAFLD group, there were obvious fatty changes in liver tissue, fat droplets in hepatocytes and inflammatory cell infiltration. And the mRNA and protein expressions of NLRP3, ASC, caspase-1 and the protein expression of Ser636-IRS-1 in NAFLD group were increased significantly, and the contents of interleukin 1ß (IL-1ß) and interleukin 18 (IL-18) in liver and serum were increased, while the mRNA and protein expressions of IRS-1 and GLUT4 and Tyr465-IRS-1 were decreased significantly (P<0.05). Compared with NAFLD group, the above indexes of GPR81 agonist group were all significantly improved. Conclusion: The activation of NLRP3 signaling pathway mediates the production of inflammatory factors and promotes the development of NAFLD. GPR81 agonist may be a potential treatment for NAFLD.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Insulina , Fígado , Masculino , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G
11.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360563

RESUMO

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the "modern" Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin-GH-IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin-GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.


Assuntos
Envelhecimento/patologia , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/patologia , Hiperinsulinismo/complicações , Resistência à Insulina , Neoplasias/patologia , Obesidade/patologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Humanos , Neoplasias/etiologia
12.
BMJ Case Rep ; 14(8)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340988

RESUMO

A 42 year-old Caribbean woman with, known type 2 diabetes, was admitted with worsening fatigue, arthritis and rashes. She was diagnosed with multisystem systemic lupus erythematosus and was initially treated with systemic steroids. During this admission, she had persistently elevated capillary glucose levels with insulin requirements over 8 U/kg/day that still did not control her blood glucose levels. Due to her profound hyperglycaemia, serum samples of fasting insulin, C-peptide, paired with blood glucose were analysed, which confirmed significant hyperinsulinaemia. Further analysis confirmed the presence of insulin receptor antibodies consistent with type B insulin resistance.She was started on intravenous cyclophosphamide (Euro-Lupus regimen) along with continuous glucose monitoring system. After completing her six cycles of cyclophosphamide, she no longer required insulin treatment. The goal of therapy for our patient with confirmed type B insulin resistance was to manage hyperglycaemia with high doses of insulin until autoantibodies were eliminated with immunosuppressive therapy.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Lúpus Eritematoso Sistêmico , Adulto , Glicemia , Automonitorização da Glicemia , Região do Caribe , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico
13.
Reprod Health ; 18(1): 171, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407851

RESUMO

BACKGROUND: Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS. METHODS: We identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed. RESULTS: Twenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + D-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31-93.58]). Myo-inositol + D-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: - 0.72 [95% CI (- 1.11)-(- 0.34)] to - 0.89 [95% CI (- 1.460)-(- 0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. CONCLUSIONS: Ours is the first study to report that for women with PCOS, myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with D-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registration PROSPERO CRD42020211524.


Assuntos
Berberina , Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , Tiazolidinedionas , Tomada de Decisão Clínica , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Inositol/uso terapêutico , Insulina , Metaboloma , Metformina/uso terapêutico , Metanálise em Rede , Síndrome do Ovário Policístico/tratamento farmacológico , Tiazolidinedionas/uso terapêutico , Incerteza
14.
J Agric Food Chem ; 69(32): 9238-9248, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34357772

RESUMO

This study aimed to investigate pharmacokinetic variables of two doses of red raspberry (RR) (poly)phenols and their association with metabolic indices in adults with prediabetes and insulin resistance (preDM-IR) compared to metabolically healthy adults (reference). Thirty-two adults (preDM-IR, n = 21; reference, n = 11) consumed three meals containing 0 g (control), 125 g, or 250 g of frozen RR on three separate days in random order. Plasma (poly)phenolic metabolites and metabolic indices were characterized over a 0-8 h period and again at 24 h. Twenty-four metabolites were significantly increased by RR interventions in all subjects (p < 0.05). Individuals with preDM-IR compared to reference had a lower capacity to generate several metabolites, including 4'-hydroxy-3'-methoxycinnamic acid and hydroxymethoxycinnamic acid isomer, both negatively correlated with postprandial insulin concentrations (p < 0.05). The results suggest that RR (poly)phenols are metabolized in a dose-related manner, and further research is required to understand their role in insulin management.


Assuntos
Resistência à Insulina , Estado Pré-Diabético , Rubus , Adulto , Glicemia , Humanos , Insulina , Fenóis , Estado Pré-Diabético/tratamento farmacológico
15.
Niger J Clin Pract ; 24(8): 1240-1246, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34397037

RESUMO

Background: The serum adiponectin level (AD), adiponectin resistance (AD-R) may reflect the degree of metabolic syndrome (MetS). The role parameter AD-R, The Homeostasis Model Assessment-Adiponectin (HOMA-AD) index on the coronary artery disease (CAD) severity is not still understood. Objective: To determine adiponectin concentration and HOMA-AD index in patients with CAD with/without MetS and to evaluate their prognostic importance on severity of CAD. Methods: This cross-sectional study involved selected 130 examinees which were divided into three groups: CAD+MetS, CAD-MetS, control group (no CAD/MetS). In all examinees values of biochemical and anthropometric parameters were determined. We analyzed the severity of coronary artery lesions from coronary angiography. Total serum adiponectin concentration was measured by ELISA. We calculated atherogenic Gensini scoring system, Duke prognostic index, and HOMA-AD-index. Results: Serum adiponectin level was significantly lower in the group with CAD+MetS (p < 0.001) and in CAD-MetS group (p < 0.01), compared to the control group. The HOMA-AD index showed statistically significant positive correlation with the key parameters of MetS, as well as with the parameters of CAD, number of CAD and modified Gensini score. After applying logistic regression analysis the best predictors for CAD were: adiponectin, blood pressure, HOMA-IR index, and HOMA-AD index. The cut-off values of adiponectin ≤1506.38 pg/mL, HOMA-IR index ≥3.91 and HOMA-AD index ≥0.67 were associated with a higher risk of CAD. Conclusion: Patients with CAD with or without MetS had low adiponectin levels and this hypoadiponectinemia indicates that AD and HOMA-AD index may be a useful marker for identifying patients at risk for CAD.


Assuntos
Doença da Artéria Coronariana , Resistência à Insulina , Síndrome Metabólica , Adiponectina , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia
16.
J Assoc Physicians India ; 69(7): 11-12, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34431270

RESUMO

BACKGROUND: Atherosclerotic cardiovascular diseases are the leading cause of morbidity and mortality in both diabetics and prediabetics. In insulin resistant states, increased levels of various adipose derived cytokine (adipokine) have been found to have an important role in the process of atherosclerosis. One such novel adipokine is RBP4, (belonging to lipokalin family) which also by exerting an inflammatory process has a role in the pathogenesis of insulin resistance and CVD.. Early detection of all these inflammatory cytokines may immensely help us in prognosticating the pace of disease besides instituting early interventional manuevers. OBJECTIVE: The aim of the study was to compare serum levels of RBP4 in prediabetics and controls and to correlate levels of RBP4 with HOMA-IR and CIMT. METHODS: 60 prediabetic patients and 60 age, sex, BMI matched controls were employed in the case control study. In both cases and controls serum levels of fasting and postprandial blood glucose, glycated hemoglobin (HbA1c) and fasting insulin levels were measured. HOMA-IR values in both the groups were calculated using fasting glucose and insulin levels. Serum RBP4 levels were measured using ELISA. The values obtained were compared between cases and controls. CIMT was only measured in cases using B-mode ultrasonography. RESULTS: Median (IQR) of fasting plasma insulin levels (uIU/ml)in cases was 11.3 (10.175-13.505) versus that of controls which was 5.73 (4.3-7.1). HOMA-IR median (IQR) in cases and controls was 3.12 (2.73-3.595) and 1.21(0.918-1.505) respectively. Median (IQR) for RBP4 in cases was 67.4 (46.166-111.088) which was significantly higher as compared to controls 33.92 (23.902-52.45). Significant positive correlation was seen between RBP4 with both, HOMA-IR and mean CIMT with correlation coefficients of 0.3693 and 0.621 respectively. On performing univariate linear regression analysis it was found that with increase in serum RBP4 levels by 1 mg/L, HOMA-IR and mean CIMT significantly increased by 0.007 units and 0.001 mm respectively. METHODS: 60 prediabetic patients and 60 age, sex, BMI matched controls were employed in the case control study. In both cases and controls serum levels of fasting and postprandial blood glucose, glycated hemoglobin (HbA1c) and fasting insulin levels were measured. HOMA-IR values in both the groups were calculated using fasting glucose and insulin levels. Serum RBP4 levels were measured using ELISA. The values obtained were compared between cases and controls. CIMT was only measured in cases using B-mode ultrasonography. CONCLUSION: Prediabetics have been found to have more risk of cardiovascular events as compared to normoglycemics. Early assessment of the same with the use of novel biomarkers like RBP4 can be considered for early detection of atherosclerosis in prediabetic individuals. It may further help in early intervention and thus prevention from future complications.


Assuntos
Aterosclerose , Resistência à Insulina , Estado Pré-Diabético , Biomarcadores , Estudos de Casos e Controles , Humanos , Estado Pré-Diabético/diagnóstico , Proteínas Plasmáticas de Ligação ao Retinol
17.
Nat Commun ; 12(1): 5068, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417460

RESUMO

p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.


Assuntos
Acetilglucosamina/metabolismo , Glucose/metabolismo , Fígado/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Sequência de Bases , Restrição Calórica , Linhagem Celular , Colforsina/farmacologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Epinefrina/metabolismo , Glucagon/metabolismo , Glucocorticoides/metabolismo , Gluconeogênese/efeitos dos fármacos , Glicosilação , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hidrocortisona/metabolismo , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/complicações , Obesidade/metabolismo , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Ácido Pirúvico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Genética/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética
18.
FASEB J ; 35(9): e21752, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34369602

RESUMO

Aging, obesity, and insulin resistance are associated with low levels of PGC1α and PGC1ß coactivators and defective mitochondrial function. We studied mice deficient for PGC1α and PGC1ß [double heterozygous (DH)] to investigate their combined pathogenic contribution. Contrary to our hypothesis, DH mice were leaner, had increased energy dissipation, a pro-thermogenic profile in BAT and WAT, and improved carbohydrate metabolism compared to wild types. WAT showed upregulation of mitochondriogenesis/oxphos machinery upon allelic compensation of PGC1α4 from the remaining allele. However, DH mice had decreased mitochondrial OXPHOS and biogenesis transcriptomes in mitochondria-rich organs. Despite being metabolically healthy, mitochondrial defects in DH mice impaired muscle fiber remodeling and caused qualitative changes in the hepatic lipidome. Our data evidence first the existence of organ-specific compensatory allostatic mechanisms are robust enough to drive an unexpected phenotype. Second, optimization of adipose tissue bioenergetics is sufficient to maintain a healthy metabolic phenotype despite a broad severe mitochondrial dysfunction in other relevant metabolic organs. Third, the decrease in PGC1s in adipose tissue of obese and diabetic patients is in contrast with the robustness of the compensatory upregulation in the adipose of the DH mice.


Assuntos
Tecido Adiposo/metabolismo , Mitocôndrias/genética , Proteínas Nucleares/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Fatores de Transcrição/genética , Envelhecimento/genética , Animais , Modelos Animais de Doenças , Metabolismo Energético/genética , Heterozigoto , Resistência à Insulina/genética , Masculino , Camundongos , Obesidade/genética , Termogênese/genética , Transcriptoma/genética
19.
Braz J Med Biol Res ; 54(10): e11391, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34406209

RESUMO

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,ß-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Proteínas Quinases Ativadas por AMP , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ácido Oleanólico/análogos & derivados , Proteína de Ligação a Elemento Regulador de Esterol 1
20.
Nutrients ; 13(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34371968

RESUMO

In recent decades, the prevalence of obesity has risen dramatically worldwide among all age groups. Obesity is characterized by excess fat accumulation and chronic low-grade inflammation. The adipose tissue functions as a metabolically active endocrine organ secreting adipokines. A novel duo of adipokines, the anti-inflammatory secreted frizzled-related protein 5 (Sfrp5) and the proinflammatory wingless type mouse mammary tumor virus (MMTV) integration site family member 5A (Wnt5a), signal via the non-canonical Wnt pathway. Recent evidence suggests that Sfpr5 and Wnt5a play a key role in the pathogenesis of obesity and its metabolic complications. This review summarizes the current knowledge on the novel regulatory system of anti-inflammatory Sfrp5 and pro-inflammatory Wnt5a, and their relation to obesity and obesity-related complications. Future studies are required to investigate the potential role of Sfrp5 and Wnt5a as biomarkers for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors. These adipokines may also serve as novel therapeutic targets for obesity-related disorders.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Obesidade/etiologia , Proteína Wnt-5a/fisiologia , Tecido Adiposo/fisiopatologia , Adolescente , Adulto , Animais , Fatores de Risco Cardiometabólico , Criança , Dieta Saudável , Humanos , Inflamação/fisiopatologia , Resistência à Insulina , Estilo de Vida , Hepatopatia Gordurosa não Alcoólica , Obesidade/fisiopatologia , Obesidade/terapia
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