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1.
Int J Mol Sci ; 22(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34639136

RESUMO

BACKGROUND: α-cyclodextrin (α-CD) is one of the dietary fibers that may have a beneficial effect on cholesterol and/or glucose metabolism, but its efficacy and mode of action remain unclear. METHODS: In the present study, we examined the anti-hyperglycemic effect of α-CD after oral loading of glucose and liquid meal in mice. RESULTS: Administration of 2 g/kg α-CD suppressed hyperglycemia after glucose loading, which was associated with increased glucagon-like peptide 1 (GLP-1) secretion and enhanced hepatic glucose sequestration. By contrast, 1 g/kg α-CD similarly suppressed hyperglycemia, but without increasing secretions of GLP-1 and insulin. Furthermore, oral α-CD administration disrupts lipid micelle formation through its inclusion of lecithin in the gut luminal fluid. Importantly, prior inclusion of α-CD with lecithin in vitro nullified the anti-hyperglycemic effect of α-CD in vivo, which was associated with increased intestinal mRNA expressions of SREBP2-target genes (Ldlr, Hmgcr, Pcsk9, and Srebp2). CONCLUSIONS: α-CD elicits its anti-hyperglycemic effect after glucose loading by inducing lecithin inclusion in the gut lumen and activating SREBP2, which is known to induce cholecystokinin secretion to suppress hepatic glucose production via a gut/brain/liver axis.


Assuntos
Trato Gastrointestinal/metabolismo , Hiperglicemia/prevenção & controle , Lecitinas/metabolismo , Período Pós-Prandial , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , alfa-Ciclodextrinas/farmacologia , Animais , Trato Gastrointestinal/efeitos dos fármacos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína de Ligação a Elemento Regulador de Esterol 2/genética
2.
J Investig Med High Impact Case Rep ; 9: 23247096211051927, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34654335

RESUMO

The differential diagnosis for peripheral neuropathy of uncertain etiology is extensive, and the work-up presents a diagnostic challenge for the physician. Following initial clinical assessment, we recommend electrodiagnostic studies as the test of choice in the evaluation of peripheral neuropathy of unclear cause. Subsequent laboratory testing can then be better specified according to the results of the electrodiagnostic studies and clinical assessment. This case report presents a 66-year-old female with a history of uncontrolled type-II diabetes who developed prominent sensorimotor neuropathy after experiencing several hypoglycemic episodes. Due to difficulties with insulin titration, over the course of 4 weeks, the patient quickly and drastically lowered her chronically elevated average serum glucose concentration to the point of suffering multiple periods of hypoglycemia. Soon after, she developed paresthesia in her hands and feet, as well as significant weakness in both upper and lower extremities. Unfortunately, the patient was lost to follow-up before a definitive diagnosis could be established. Hypoglycemia and rapid correction of long-standing hyperglycemia are relatively under-recognized sources of neuropathy in diabetic patients. Physicians taking care of diabetic patients who develop peripheral neuropathy following rapidly improved glycemic control or hypoglycemia should be aware of the possibility of a diabetic neuropathy and begin prompt work-up to exclude other causes before making the diagnosis of treatment-induced diabetic neuropathy or hypoglycemic neuropathy.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Hiperglicemia , Polineuropatias , Idoso , Neuropatias Diabéticas/diagnóstico , Feminino , Humanos , Hiperglicemia/etiologia , Insulina , Polineuropatias/diagnóstico , Polineuropatias/etiologia
3.
Nutrients ; 13(10)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34684559

RESUMO

Carbohydrate counting (CHC) is the established form of calculating bolus insulin for meals in children with type 1 diabetes (T1DM). With the widespread use of continuous glucose monitoring (CGM) observation time has become gapless. Recently, the impact of fat, protein and not only carbohydrates on prolonged postprandial hyperglycaemia have become more evident to patients and health-care professionals alike. However, there is no unified recommendation on how to calculate and best administer additional bolus insulin for these two macronutrients. The aim of this review is to investigate: the scientific evidence of how dietary fat and protein influence postprandial glucose levels; current recommendations on the adjustment of bolus insulin; and algorithms for insulin application in children with T1DM. A PubMed search for all articles addressing the role of fat and protein in paediatric (sub-)populations (<18 years old) and a mixed age population (paediatric and adult) with T1DM published in the last 10 years was performed. Conclusion: Only a small number of studies with a very low number of participants and high degree of heterogeneity was identified. While all studies concluded that additional bolus insulin for (high) fat and (high) protein is necessary, no consensus on when dietary fat and/or protein should be taken into calculation and no unified algorithm for insulin therapy in this context exists. A prolonged postprandial observation time is necessary to improve individual metabolic control. Further studies focusing on a stratified paediatric population to create a safe and effective algorithm, taking fat and protein into account, are necessary.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Ingestão de Alimentos/fisiologia , Controle Glicêmico/métodos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adolescente , Algoritmos , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Gorduras na Dieta/análise , Proteínas na Dieta/análise , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Hiperglicemia/etiologia , Hiperglicemia/prevenção & controle , Sistemas de Infusão de Insulina , Masculino , Período Pós-Prandial/fisiologia
4.
J Assoc Physicians India ; 69(9): 11-12, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34585892

RESUMO

SARS-CoV-2 virus spread rapidly all over the globe in 2020 and the second wave has taken our nation, India by storm. The pandemic has posed unique challenges in people with metabolic disorders, including diabetes, hypertension, obesity, pulmonary, cardiovascular, kidney and non-alcoholic fatty liver disease. Uncontrolled diabetes, in conjunction with endocrine, inflammatory and metabolic effects of the infection itself has made management of hyperglycemia in COVID-19 infection particularly challenging. Furthermore, the post-COVID-19 syndrome has also emerged as a sequela in COVID-19 survivors, increasing the risk of death, complications and adding further burden on the health care system. With more than a year of experience, we have gained substantial insight; and now provide practical recommendations on the management of hyperglycemia in COVID-19 as well as post COVID-19 syndrome.


Assuntos
COVID-19 , Hiperglicemia , COVID-19/complicações , Humanos , Hiperglicemia/etiologia , Hiperglicemia/terapia , Índia/epidemiologia , SARS-CoV-2
5.
Nutrients ; 13(9)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34578791

RESUMO

Prediabetes is a strong predictor of type 2 diabetes and its associated cardiovascular complications, but few studies explore sexual dimorphism in this context. Here, we aim to determine whether sex influences physiological response to high-fat high-sucrose diet (HFS) and myocardial tolerance to ischemia-reperfusion injury. Male and female Wistar rats were subjected to standard (CTRL) or HFS diet for 5 months. Then, ex-vivo experiments on isolated perfused heart model were performed to evaluate tolerance to ischemia-reperfusion injury. HFS diet induced fasting hyperglycemia and increased body fat percent to a similar level in both sexes. However, glucose intolerance was more pronounced in female HFS. Cholesterol was increased only in female while male displayed higher level of plasmatic leptin. We observed increased heart weight to tibia length ratio only in males, but we showed a similar decrease in tolerance to ischemia-reperfusion injury in female and male HFS compared with respective controls, characterized by impaired cardiac function, energy metabolism and coronary flow during reperfusion. In conclusion, as soon as glucose intolerance and hyperglycemia develop, we observe higher sensitivity of hearts to ischemia-reperfusion injury without difference between males and females.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/efeitos adversos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Animais , Colesterol/sangue , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético , Feminino , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Leptina/sangue , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo , Estado Pré-Diabético/metabolismo , Ratos , Ratos Wistar , Fatores Sexuais , Ganho de Peso
6.
Nat Commun ; 12(1): 5616, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556670

RESUMO

Coptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet ß-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels.


Assuntos
Berberina/farmacologia , Canais de Potássio Éter-A-Go-Go/metabolismo , Hiperglicemia/metabolismo , Secreção de Insulina/efeitos dos fármacos , Secretagogos/farmacologia , Adolescente , Adulto , Animais , Linhagem Celular Tumoral , Estudos Cross-Over , Dieta Hiperlipídica/efeitos adversos , Canais de Potássio Éter-A-Go-Go/genética , Células HEK293 , Humanos , Hiperglicemia/etiologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Ativação do Canal Iônico/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Adulto Jovem
7.
BMC Pediatr ; 21(1): 335, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362315

RESUMO

BACKGROUND: Stress hyperglycemia (SH) is considered a transient manifestation and routine diagnostic evaluation was thought to be unnecessary due to the lack of definite correlation with diabetes mellitus (DM). Although SH was usually benign and long-term treatment was superfluous, it might be the first sign of insulinopenic status such as type 1 DM (T1DM). CASE PRESENTATION: We reported a boy with acute asthma attack presented incidentally with high blood glucose levels exceeding 300 mg/dL and obvious glycemic variability. A prolonged hyperglycemic duration of more than 48 h was also noticed. To elucidate his unique situation, glucagon test and insulin autoantibody survey were done which showed insulinopenia with positive anti-insulin antibody and glutamic acid decarboxylase antibody despite the absence of overt DM symptoms and signs. CONCLUSIONS: This case highlights that SH might be a prodromal presentation in T1DM children, especially when accompanied simultaneously with extreme hyperglycemia, apparent glucose variability, as well as prolonged hyperglycemic duration.


Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Glicemia , Criança , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/etiologia , Insulina , Anticorpos Anti-Insulina , Masculino
8.
Nutrients ; 13(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34371983

RESUMO

The worldwide prevalence of metabolic diseases such as obesity, metabolic syndrome and type 2 diabetes shows an upward trend in recent decades. A characteristic feature of these diseases is hyperglycemia which can be associated with hyperphagia. Absorption of glucose in the small intestine physiologically contributes to the regulation of blood glucose levels, and hence, appears as a putative target for treatment of hyperglycemia. In fact, recent progress in understanding the molecular and cellular mechanisms of glucose absorption in the gut and its reabsorption in the kidney helped to develop a new strategy of diabetes treatment. Changes in blood glucose levels are also involved in regulation of appetite, suggesting that glucose absorption may be relevant to hyperphagia in metabolic diseases. In this review we discuss the mechanisms of glucose absorption in the small intestine in physiological conditions and their alterations in metabolic diseases as well as their relevance to the regulation of appetite. The key role of SGLT1 transporter in intestinal glucose absorption in both physiological conditions and in diabetes was clearly established. We conclude that although inhibition of small intestinal glucose absorption represents a valuable target for the treatment of hyperglycemia, it is not always suitable for the treatment of hyperphagia. In fact, independent regulation of glucose absorption and appetite requires a more complex approach for the treatment of metabolic diseases.


Assuntos
Regulação do Apetite , Glucose/metabolismo , Hiperglicemia/metabolismo , Absorção Intestinal/fisiologia , Doenças Metabólicas/metabolismo , Humanos , Hiperglicemia/etiologia , Intestino Delgado/metabolismo , Doenças Metabólicas/complicações , Transportador 1 de Glucose-Sódio/metabolismo
9.
Nutrients ; 13(8)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34445047

RESUMO

Sargassum fusiforme alginate (SF-Alg) possess many pharmacological activities, including hypoglycemic and hypolipidemic. However, the hypoglycemic mechanisms of SF-Alg remain unclear due to its low bioavailability. In this study, we evaluated the therapeutic effect of SF-Alg on high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes (T2D) mice. SF-Alg intervention was found to significantly reduce fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC), while increasing high-density lipoprotein cholesterol (HDL-c) and improving glucose tolerance. In addition, administrating SF-Alg to diabetic mice moderately attenuated pathological changes in adipose, hepatic, and heart tissues as well as skeletal muscle, and diminished oxidative stress. To probe the underlying mechanisms, we further analyzed the gut microbiota using 16S rRNA amplicon sequencing, as well as metabolites by non-targeted metabolomics. Here, SF-Alg significantly increased some benign bacteria (Lactobacillus, Bacteroides, Akkermansia Alloprevotella, Weissella and Enterorhabdus), and significantly decreased harmful bacteria (Turicibacter and Helicobacter). Meanwhile, SF-Alg dramatically decreased branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in the colon of T2D mice, suggesting a positive benefit of SF-Alg as an adjvant agent for T2D.


Assuntos
Alginatos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Sargassum/química , Animais , Glicemia/efeitos dos fármacos , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Camundongos , Estreptozocina , Triglicerídeos/sangue
10.
Metabolism ; 123: 154845, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34364927

RESUMO

PURPOSE: Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications. METHODS: We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia. RESULTS: Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p = 0.001), fasting blood glucose (HR 4.32, p < 0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p = 0.010) or fasting blood glucose ≥7 mmol/L (HR 3.07, p = 0.015). CONCLUSIONS: Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.


Assuntos
COVID-19/epidemiologia , Diabetes Mellitus/epidemiologia , Hiperglicemia/epidemiologia , Tromboembolia/etiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/terapia , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/terapia , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/etiologia , Hiperglicemia/terapia , Inflamação/complicações , Inflamação/diagnóstico , Inflamação/epidemiologia , Inflamação/terapia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Prognóstico , Fatores de Risco , Estresse Psicológico/complicações , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Tromboembolia/diagnóstico , Tromboembolia/epidemiologia , Resultado do Tratamento
11.
J Am Soc Nephrol ; 32(8): 2083-2098, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34330770

RESUMO

BACKGROUND: Post-transplantation diabetes mellitus (PTDM) might be preventable. METHODS: This open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test-derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant. RESULTS: In the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24. CONCLUSIONS: At low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM-a significant reduction after adjustment for baseline differences-suggesting the intervention merits further study.Clinical Trial registration number: NCT03507829.


Assuntos
Diabetes Mellitus/prevenção & controle , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Isófana/uso terapêutico , Transplante de Rim/efeitos adversos , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/etiologia , Feminino , Hemoglobina A Glicada/metabolismo , Fidelidade a Diretrizes , Humanos , Hiperglicemia/sangue , Hiperglicemia/etiologia , Hipoglicemia/induzido quimicamente , Insulina Lispro/uso terapêutico , Insulina Isófana/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Período Pós-Operatório , Fatores de Risco , Fatores Sexuais , Padrão de Cuidado , Fatores de Tempo
12.
Molecules ; 26(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299566

RESUMO

Citrus fruits are a rich source of high-value bioactive compounds and their consumption has been associated with beneficial effects on human health. Red (blood) oranges (Citrus sinensis L. Osbeck) are particularly rich in anthocyanins (95% of which are represented by cyanidin-3-glucoside and cyanidin-3-6″-malonyl-glucoside), flavanones (hesperidin, narirutin, and didymin), and hydroxycinnamic acids (caffeic acid, coumaric acid, sinapic, and ferulic acid). Lemon fruit (Citrus limon) is also rich in flavanones (eriocitrin, hesperidin, and diosmin) and other polyphenols. All of these compounds are believed to play a very important role as dietary antioxidants due to their ability to scavenge free radicals. A standardized powder extract, red orange and lemon extract (RLE), was obtained by properly mixing anthocyanins and other polyphenols recovered from red orange processing waste with eriocitrin and other flavanones recovered from lemon peel by a patented extraction process. RLE was used for in vivo assays aimed at testing a potential beneficial effect on glucose and lipid metabolism. In vivo experiments performed on male CD1 mice fed with a high-fat diet showed that an 8-week treatment with RLE was able to induce a significant reduction in glucose, cholesterol and triglycerides levels in the blood, with positive effects on regulation of hyperglycemia and lipid metabolism, thus suggesting a potential use of this new phytoextract for nutraceutical purposes.


Assuntos
Citrus , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Antocianinas/química , Antocianinas/uso terapêutico , Antioxidantes/química , Antioxidantes/uso terapêutico , Citrus/química , Dieta Hiperlipídica/efeitos adversos , Flavanonas/química , Flavanonas/uso terapêutico , Hiperglicemia/etiologia , Hiperlipidemias/etiologia , Hipoglicemiantes/química , Hipolipemiantes/química , Masculino , Camundongos , Extratos Vegetais/química
13.
Nutrients ; 13(6)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199741

RESUMO

(1) Background: Recent evidence reported a reduced tolerance of macronutrient parenteral intakes in subjects in critically ill conditions. We designed a prospective cohort study to evaluate the effects of hyperglycemia (HG) related to parenteral nutrition (PN) on neurodevelopment (NDV) in survived preterm newborns. (2) Methods: Enrolled newborns with gestational age < 32 weeks or birth weight < 1500 g, were divided in two cohorts: (A) exposed to moderate or severe HG (glucose blood level > 180 mg/dL) in the first week of life; (B) not exposed to HG. We considered as the primary outcome the rate of preterm newborns survived without NDV delay at 24 months of life, evaluated with Bayley Scales of Infants Development III edition. (3) Results: We analyzed 108 (A 32 vs. B 76) at 24 months of life. Newborns in cohort A showed a higher rate of cognitive and motor delay (A 44% vs. B 22 %, p = 0.024; A 38% vs. B 8%, p < 0.001). When adjusting for background characteristics, HG remained a risk factor for motor delay. (4) Conclusions: High nutritional intakes through PN soon after birth increase the risk of HG. The consequences of this severe metabolic complication affect long-term NDV and survival in preterm newborns.


Assuntos
Hiperglicemia/etiologia , Nutrição Parenteral Total , Nutrição Parenteral , Adulto , Peso ao Nascer , Glicemia , Desenvolvimento Infantil , Estudos de Coortes , Idade Gestacional , Humanos , Hiperglicemia/mortalidade , Recém-Nascido , Doenças do Recém-Nascido , Modelos Logísticos , Idade Materna , Análise Multivariada , Transtornos do Neurodesenvolvimento/etiologia , Estudos Prospectivos
14.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199046

RESUMO

Hyperglycemia may contribute to the progression of carcinomas by triggering epithelial-to-mesenchymal transition (EMT). Some proteostasis systems are involved in metastasis; in this paper, we sought to explore the mechanism of Hsp70 chaperone in EMT. We showed that knockdown of Hsp70 reduced cell migration capacity concomitantly with levels of mRNA of the Slug, Snail, and Twist markers of EMT, in colon cancer cells incubated in high glucose medium. Conversely, treatment of cells with Hsp70 inducer U-133 were found to elevate cell motility, along with the other EMT markers. To prove that inhibiting Hsp70 may reduce EMT efficiency, we treated cells with a CL-43 inhibitor of the HSF1 transcription factor, which lowered Hsp70 and HSF1 content in the control and induced EMT in carcinoma cells. Importantly, CL-43 reduced migration capacity, EMT-linked transcription factors, and increased content of epithelial marker E-cadherin in colon cancer cells of three lines, including one derived from a clinical sample. To prove that Hsp70 chaperone should be targeted when inhibiting the EMT pathway, we treated cancer cells with 2-phenylethynesulfonamide (PES) and demonstrated that the compound inhibited substrate-binding capacity of Hsp70. Furthermore, PES suppressed EMT features, cell motility, and expression of specific transcription factors. In conclusion, the Hsp70 chaperone machine efficiently protects mechanisms of the EMT, and the safe inhibitors of the chaperone are needed to hamper metastasis at its initial stage.


Assuntos
Glicemia , Transição Epitelial-Mesenquimal , Glucose/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Biomarcadores , Caderinas/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/farmacologia , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Ligação Proteica , Fatores de Transcrição da Família Snail/metabolismo
15.
Sci Rep ; 11(1): 12374, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117292

RESUMO

Ginseng (Panax ginseng Meyer) is commonly used as an herbal remedy worldwide. Few studies have explored the possible physiological changes in the liver although patients often self-medicate with ginseng preparations, which may lead to exceeding the recommended dose for long-term administration. Here, we analyzed changes in the hepatic proteins of mouse livers using quantitative proteomics after sub-chronic administration of Korean red ginseng (KRG) extract (control group and 0.5, 1.0, and 2.0 g/kg KRG) using tandem mass tag (TMT) 6-plex technology. The 1.0 and 2.0 g/kg KRG groups exhibited signs of liver injury, including increased levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum. Furthermore, serum glucose levels were significantly higher following KRG administration compared with the control group. Based on the upregulated proteins found in the proteomic analysis, we found that increased cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) levels promoted greater hydrogen sulfide (H2S) synthesis in the liver. This investigation provides novel evidence that sub-chronic administration of KRG can elevate H2S production by increasing protein expression of CBS and CSE in the liver.


Assuntos
Hiperglicemia/etiologia , Panax/química , Extratos Vegetais/efeitos adversos , Proteômica , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Cistationina beta-Sintase/metabolismo , Relação Dose-Resposta a Droga , Humanos , Sulfeto de Hidrogênio/metabolismo , Fígado/enzimologia , Camundongos , Estresse Oxidativo , Extratos Vegetais/administração & dosagem
16.
Life Sci ; 279: 119672, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34097971

RESUMO

AIMS: Intestinal nutrient absorption plays a vital role in developing obesity, and nutrient transporters expressed in the enterocytes facilitate this process. Moreover, previous studies have shown that specific foods and diets can affect their cell levels. Herein, we investigated the effects of pequi oil (PO), which is high in several bioactive compounds, on intestinal nutrient transporter levels as well as on intestinal morphology and metabolic biomarkers. MAIN METHODS: Groups of male C57BL/6 mice were fed either a standard (C) or a high-fat diet (HFD) and pequi oil (CP and HFDP with PO by gavage at 150 mg/day) for eight weeks. Food intake and body weight were monitored, serum metabolic biomarkers, intestinal transporter levels and histological analyses were performed. KEY FINDINGS: PO increased caloric intake without increasing body or fat mass regardless of diet. The HFD group treated with PO reduced fasting blood glucose and villus width. PO did not affect GLUT2, L-FABP, FATP4, NPC1L1, NHE3 or PEPT1 content in CP or HFDP groups. GLUT5 and FAT/CD36 levels were reduced in both CP and HFDP. SIGNIFICANCE: Our data suggest that PO attenuated monosaccharide and fatty acid absorption, contributing to lower fasting glycemia and higher food intake without affecting body weight or visceral fat of high-fat feed mice.


Assuntos
Glicemia/metabolismo , Antígenos CD36/metabolismo , Carotenoides/farmacologia , Transportador de Glucose Tipo 5/metabolismo , Hiperglicemia/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Óleos Vegetais/farmacologia , Animais , Biomarcadores/metabolismo , Caderinas/metabolismo , Dieta Hiperlipídica , Ingestão de Energia , Ericales/química , Ácidos Graxos/metabolismo , Controle Glicêmico , Hiperglicemia/etiologia , Hiperglicemia/patologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações
17.
Medicine (Baltimore) ; 100(25): e26508, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160471

RESUMO

ABSTRACT: This study was conducted to examine whether Korean veterans from the US-Vietnam War who had a diagnosis of type II diabetes mellitus (T2DM) as well as past history of exposure to agent orange (AO) are vulnerable to hyperglycemia when receiving intra-articular corticosteroid injection (IACI) for pain relief.The current study included a total of 49 patients (n = 49) who received an injection of triamcinolone 20 or 40 mg to the shoulder under sonographic guidance or did that of dexamethasone 10 mg or triamcinolone 40 mg combined with dexamethasone 20 mg to the spine under fluoroscopic guidance. Their 7-day fasting blood glucose (FBG) levels were measured and then averaged, serving as baseline levels. This is followed by measurement of FBG levels for 14 days of IACI. Respective measurements were compared with baseline levels. The patients were also evaluated for whether there are increases in FBG levels depending on insulin therapy as well as HbA1c ≥ 7% or HbA1c < 7%.Overall, there were significant increases in FBG levels by 64.7 ±â€Š42.5 mg/dL at 1 day of IACI from baseline (P < .05). HbA1c ≥ 7% and HbA1c < 7% showed increases in FBG levels by 106.1 ±â€Š49.0 mg/dL and 46.5 ±â€Š3.8 mg/dL, respectively, at 1 day of IACI from baseline (P < .05). In the presence and absence of insulin therapy, there were significant increases in them by 122.6 ±â€Š48.7 mg/dL and 48.0 ±â€Š20.4 mg/dL, respectively, at 1 day of IACI from baseline (P < .05). But there were decreases in them to baseline levels at 2 days of IACI.Clinicians should consider the possibility of hyperglycemia when using corticosteroids for relief of musculoskeletal pain in Korean veterans from the US-Vietnam War who had a history of exposure to AO.


Assuntos
Agente Laranja/efeitos adversos , Artralgia/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Glucocorticoides/efeitos adversos , Hiperglicemia/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Idoso , Glicemia/análise , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Hiperglicemia/etiologia , Injeções Intra-Articulares , Insulina/administração & dosagem , Masculino , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia , Triancinolona/administração & dosagem , Triancinolona/efeitos adversos , Veteranos/psicologia , Veteranos/estatística & dados numéricos , Guerra do Vietnã , Exposição à Guerra/efeitos adversos
18.
Hemoglobin ; 45(2): 124-128, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34162301

RESUMO

This study aimed to examine the relationship between Hb A1c levels and the clinical course of coronavirus-19 (COVID-19) patients. Sixty-six COVID-19(+) patients with high Hb A1c and 46 with average Hb A1c and 30 COVID-19(-) patients with average Hb A1c were included. Hb A1c levels and parameters examined in COVID-19(+) patients were compared between groups, and correlation analysis was performed between these parameters and Hb A1c levels. The effect of Hb A1c levels on intensive care unit (ICU) admission and mortality rate in COVID-19 patients was analyzed with the χ2 test. It was observed that hemoglobin (Hb) and arterial oxygen saturation (SaO2) levels of the COVID-19 (+) groups was lower than the COVID-19 (-) group, while ferritin, D-dimer, procalcitonin (PCT), and C-reactive protein (CRP) levels were higher. The COVID-19 (+) group with high Hb A1c had higher lactate dehydrogenase (LDH), PCT and D-dimer levels than the other two groups, while Hb, partial arterial oxygen pressure (PaO2) levels were lower. The Hb A1c levels of the COVID-19 (+) groups were positively correlated with absolute neutrophil count (ANC), LDH, PCT and (K+) levels, while negatively correlated with Hb and PaO2 levels. Hb A1c was found to be associated with the inflammation process, coagulation disorders and low PaO2 in COVID-19 patients. The COVID-19 patients with high Hb A1c levels had a higher mortality rate than other COVID-19 patients. Using Hb A1c measurements with other prognostic markers would contribute to the patient's risk of death assessment.


Assuntos
COVID-19/sangue , Diabetes Mellitus/sangue , Hemoglobina A Glicada/análise , Hiperglicemia/sangue , SARS-CoV-2 , Adulto , Idoso , Sedimentação Sanguínea , Proteína C-Reativa/análise , COVID-19/complicações , COVID-19/mortalidade , Cuidados Críticos/estatística & dados numéricos , Complicações do Diabetes/sangue , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Hiperglicemia/etiologia , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Oxigênio/sangue , Pressão Parcial , Pró-Calcitonina/sangue , Prognóstico , Risco , Índice de Gravidade de Doença , Trombofilia/sangue , Trombofilia/etiologia
19.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068151

RESUMO

Severe burns represent an important challenge for patients and medical teams. They lead to profound metabolic alterations, trigger a systemic inflammatory response, crush the immune defense, impair the function of the heart, lungs, kidneys, liver, etc. The metabolism is shifted towards a hypermetabolic state, and this situation might persist for years after the burn, having deleterious consequences for the patient's health. Severely burned patients lack energy substrates and react in order to produce and maintain augmented levels of glucose, which is the fuel "ready to use" by cells. In this paper, we discuss biological substances that induce a hyperglycemic response, concur to insulin resistance, and determine cell disturbance after a severe burn. We also focus on the most effective agents that provide pharmacological modulations of the changes in glucose metabolism.


Assuntos
Glicemia/metabolismo , Queimaduras/complicações , Hiperglicemia/etiologia , Resistência à Insulina , Animais , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/patologia
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