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1.
Orv Hetil ; 161(5): 193-197, 2020 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-31984772

RESUMO

Mortality in type 1 diabetes, although showing a declining trend, is significantly higher than standard mortality. The case study focuses on a woman who lived for 91 years; she was insulin-dependent for 86 years and has been treated by a single physician - the author - for over 55 years. She was diagnosed with diabetes in 1932 at the age of five. Her diabetes was first treated with rapid-acting insulin three times daily, then from 1940 with rapid-acting and protamine zinc insulin once daily, while later on pork, then human crystalline zinc insulin was used, followed by a mixture of rapid-acting and NPH insulin for the last 16 years. The reason behind the above treatment regimen was that the patient obsessively insisted on a once daily insulin dose and the duration was shown to be 24 hours for each insulin. The continuous overdose of a single insulin for decades has resulted in hypoglycemic episodes almost daily, with consequent high fluctuations in blood glucose levels. She performed urine glucose tests using a polarimeter from the mid-1930s to the sixties, then used test strips until the early eighties, and later switched to blood glucose self-testing. Her HbA1c levels have been around 7% (53 mmol/mol) for the last 25 years. She did not develop retinopathy or nephropathy, only severe neuropathy caused complaints during the last years of her life. In addition, her vision continued to deteriorate due to age-related dry macular degeneration. She is a Joslin 75-year medalist. For the last two months of her life, she gave permission for degludec + glulisine insulin intensive treatment. Her death was caused by myocardial infarction. Although minimizing blood glucose fluctuations and sustaining good metabolic control significantly improve the life expectancy of people with diabetes, in our case neither has existed for well over half a century. Therefore, no explanation was found for the extremely long duration of diabetes and longevity. Orv Hetil. 2020; 161(5): 193-197.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Infarto do Miocárdio/mortalidade , Idoso de 80 Anos ou mais , Glicemia , Evolução Fatal , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Insulina , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Infarto do Miocárdio/complicações , Resultado do Tratamento
2.
Rev Med Liege ; 75(1): 60-66, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31920046

RESUMO

The shift to injection therapy, after failure of oral antidiabetic agents, is often considered as a difficult step by both the patient with type 2 diabetes and the physician, a situation that may lead to clinical inertia. Schematically, two options may be considered, either starting insulin therapy with a preference for basal insulin analogues, or adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA). Each option has its advantages and disadvantages, which opens the road to personalized medicine. Nevertheless, the preference is increasingly given to GLP-1 AR, yet this solution is more limited by reimbursement conditions. A combination of the two approaches is also possible, with the recent commercialisation of fixed-ratio specialities combining a basal insulin analogue and a GLP-1 RA. This clinical case offers the opportunity to discuss all these different therapeutic options in a patient with poorly controlled type 2 diabetes despite a combination of oral antidiabetic agents, taking also into account the current conditions for reimbursement in Belgium.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Administração Oral , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem
3.
Toxicol Lett ; 320: 19-27, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778773

RESUMO

The deleterious effects of glucocorticoids on glucose homeostasis limit their clinical use. There is substantial evidence demonstrating that islet function impaired by long-term glucocorticoids exposure is a core defect in the progression of impaired glucose tolerance to diabetes. The activity of heat-shock protein (Hsp) 90 is required to maintain the hormone-binding activity and stability of glucocorticoid receptor (GR). In the present study, Hsp90 inhibition by 17-DMAG counteracted dexamethasone-mediated inhibition of glucose-stimulated insulin secretion in isolated rat islets as well as expressions of neuropeptide Y (NPY) and somatostatin receptor 3 (SSTR3), two negative regulators of insulin secretion. Like 17-DMAG, both the pan-histone deacetylase (HDAC) inhibitor TSA and HDAC6 inhibitor Tubacin exhibited a similar action in protecting islet function against dexamethasone-induced injury, along with the downregulation of NPY and SSTR3 expressions. The hyperacetylation of Hsp90 by TSA and Tubacin disrupted its binding ability to GR and blocked dexamethasone-elicited nuclear translocation of GR in INS-1 ß-cell lines. In addition, Tubacin treatment triggered the GR protein degradation through the ubiquitin-proteasome pathway. These findings suggest that Hsp90 acetylation by inhibiting HDAC6 activity may be a potential strategy to prevent the development of steroid diabetes mellitus via alleviating glucocorticoid-impaired islet function.


Assuntos
Anilidas/farmacologia , Benzoquinonas/farmacologia , Dexametasona/toxicidade , Glucocorticoides/toxicidade , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Desacetilase 6 de Histona/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Lactamas Macrocíclicas/farmacologia , Acetilação , Animais , Linhagem Celular , Proteínas de Choque Térmico HSP90/metabolismo , Desacetilase 6 de Histona/metabolismo , Ilhotas Pancreáticas/metabolismo , Masculino , Complexo de Endopeptidases do Proteassoma/metabolismo , Processamento de Proteína Pós-Traducional , Proteólise , Ratos Sprague-Dawley , Via Secretória , Técnicas de Cultura de Tecidos
4.
Expert Opin Ther Pat ; 30(1): 27-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31771391

RESUMO

Introduction: The activation of free fatty acid receptor 1 (FFAR1) induces insulin secretion in a glucose-dependent manner, and thereby is considered as an attractive anti-diabetic target. The clinical studies provided a lot of evidence that FFAR1 agonists improved glucose control in T2DM without the risk of hypoglycemia. The field of FFAR1 agonists is extremely competitive with many patent applications filed in recent years identifying potent candidates.Area covered: The present review summarizes patent applications (2016-2019) filing for FFAR1 modulators, including FFAR1 partial/full agonists, atypical agonists, and multiple target agonists, along with in vitro and in vivo evaluation.Expert opinion: The clinical studies of FFAR1 agonists have proved their potential for the improvement of glucose control. However, there are a few issues still to be solved in this field since TAK-875 terminated in Phase III studies due to liver toxicity. The biggest challenge on the development of FFAR1 agonists may not be the identification of a highly potent compound, but finding out the exact mechanisms of hepatotoxicity and avoid it. Moreover, the further exploration of chemical spaces on FFAR1 full agonists and multi-targeted agonists, as well as corresponding clinical studies, will be expected and might open up new directions in this field.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Animais , Benzofuranos/efeitos adversos , Benzofuranos/farmacologia , Diabetes Mellitus Tipo 2/fisiopatologia , Desenvolvimento de Medicamentos , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Patentes como Assunto , Receptores Acoplados a Proteínas-G/metabolismo , Sulfonas/efeitos adversos , Sulfonas/farmacologia
5.
Food Chem Toxicol ; 135: 110953, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707032

RESUMO

Edible Sonchus oleraceus Linn is a medicinal plant with many bioactivities such as anti-diabetic activity and anti-inflammatory activity. However, the main bioactive components such as polyphenols in S. oleraceus Linn are poorly absorbed in gastrointestinal tract and rapidly metabolized. Thereby, a self-emulsifying delivery system containing S. oleraceus Linn extracts (SSEDDS) was introduced to evade these problems. Herein, the anti-inflammatory effect of SSEDDS on streptozotocin-induced diabetic rats was investigated. The plasma glucose level was increased and plasma insulin level was decreased in diabetic rats. The levels of NF-κB, TNF-α, and IL-6 in the liver were significantly improved in diabetic rats (p < 0.05). Conversely, daily fed diabetic rats with 100, 200 and 400 mg/kg/day of SSEDS and 1 mg/kg/day metformin for 4 weeks, significantly (p < 0.05) restored all the above mentioned parameters to near normal levels. The immuno-histochemical studies confirmed the anti-inflammatory effects of SSEDDS.


Assuntos
Anti-Inflamatórios/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Emulsões/uso terapêutico , Extratos Vegetais/uso terapêutico , Sonchus/química , Animais , Glicemia/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Ratos Sprague-Dawley , Estreptozocina
6.
Food Chem Toxicol ; 135: 110965, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31743741

RESUMO

Perilla oil (PerO), a natural oil with a high unsaturated fatty acid content derived from the mature seeds of Perilla frutescens, is a homology of medicine and food. The type 2 diabetes mellitus (T2DM) model was successfully established using a high-fat and high-sugar diet combined with a single low-dose of streptozocin (STZ). PerO intervention reduced the levels of fasting blood glucose and the level, size and accumulation of lipid droplets, increased the insulin level and diminished the body weight loss. PerO pretreatment markedly promoted the serum levels of alanine transaminase (ALT) and aspartate transaminase alanine (AST) and inhibited the levels of glucose (GLU), glucose-6-phosphate dehydrogenase (G6PD), triglycerides (TGs) and total cholesterol (TC). Moreover, PerO treatment enhanced the expression of phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and activated the expression of glucose transporter 4 (Glut4) and phospho-AKT serine/threonine kinase (p-AS160) in the liver. Additionally, PerO treatment distinctly decreased the abundance of Aerococcus and facilitated the richness of Alloprevotella in the intestine, as well as accelerated the restoration of the gut microflora diversity. Thus, PerO regulates intestinal microbiota and alleviates insulin resistance through the PI3K/AKT signaling pathway in type-2 diabetic KKAy mice and may be a potential functional food for diabetic treatment.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina/fisiologia , Transdução de Sinais/efeitos dos fármacos , Ácido alfa-Linoleico/uso terapêutico , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/fisiopatologia , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Perilla/química , Fosfatidilinositol 3-Quinase/metabolismo , Óleos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estreptozocina
7.
Adv Exp Med Biol ; 1131: 943-963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646540

RESUMO

Insulin secretion in humans is usually induced by mixed meals, which upon ingestion, increase the plasma concentration of glucose, fatty acids, amino acids, and incretins like glucagon-like peptide 1. Beta-cells can stay in the off-mode, ready-mode or on-mode; the mode-switching being determined by the open state probability of the ATP-sensitive potassium channels, and the activity of enzymes like glucokinase, and glutamate dehydrogenase. Mitochondrial metabolism is critical for insulin secretion. A sound understanding of the intermediary metabolism, electrophysiology, and cell signaling is essential for comprehension of the entire spectrum of the stimulus-secretion coupling. Depolarization brought about by inhibition of the ATP sensitive potassium channel, together with the inward depolarizing currents through the transient receptor potential (TRP) channels, leads to electrical activities, opening of the voltage-gated calcium channels, and exocytosis of insulin. Calcium- and cAMP-signaling elicited by depolarization, and activation of G-protein-coupled receptors, including the free fatty acid receptors, are intricately connected in the form of networks at different levels. Activation of the glucagon-like peptide 1 receptor augments insulin secretion by amplifying calcium signals by calcium induced calcium release (CICR). In the treatment of type 2 diabetes, use of the sulfonylureas that act on the ATP sensitive potassium channel, damages the beta cells, which eventually fail; these drugs do not improve the cardiovascular outcomes. In contrast, drugs acting through the glucagon-like peptide-1 receptor protect the beta-cells, and improve cardiovascular outcomes. The use of the glucagon-like peptide 1 receptor agonists is increasing and that of sulfonylurea is decreasing. A better understanding of the stimulus-secretion coupling may lead to the discovery of other molecular targets for development of drugs for the prevention and treatment of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Cálcio/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Glucose , Humanos , Insulina , Células Secretoras de Insulina/enzimologia , Células Secretoras de Insulina/patologia
8.
Internist (Berl) ; 61(1): 102-109, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31863132

RESUMO

The artificial pancreas (also referred to as closed-loop system) brings us one step closer to the decade-long dream of automated insulin delivery. The closed-loop system directs subcutaneous insulin delivery corresponding to the glucose concentration using a control algorithm. Evidence shows that closed-loop systems substantially improve glucose control and quality of life; however, fully automated closed-loop systems have not yet been accomplished. Active input from patients is required for mealtime insulin dosing and corrections. This article provides an overview on the current state of development of the artificial pancreas in the treatment of diabetes.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Insulina/uso terapêutico , Pâncreas Artificial , Algoritmos , Humanos , Hipoglicemia/prevenção & controle , Qualidade de Vida
10.
J Endod ; 46(1): 74-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31843129

RESUMO

INTRODUCTION: Histidine-tryptophan-ketoglutarate (HTK) is a preservation solution used for organ transplantation. The physiological pH and osmolality of this solution are known to facilitate cell proliferation and cell membrane stabilization. The purpose of the present study was to investigate the efficacy of several concentrations of HTK solution as a storage medium for avulsed teeth. METHODS: Cultured human periodontal ligament cells were stored in different concentrations of HTK solutions. After 1, 3, 6, 12, 24, 48, and 72 hours, cell viability was assessed using the Cell-Counting Kit-8 (Dojindo Molecular Technologies, Kumamoto, Japan) and LIVE/DEAD (Invitrogen, Carlsbad, CA) assay. Cell response of the most effective concentrations of HTK solution were further analyzed by gene expression profiling, and their cell viability was compared with other storage media. RESULTS: The highest cell viability was observed in 50% HTK solution in various concentrations of HTK solution (P < .05). In periodontal ligament cells stored in 50% HTK solution for 3 hours, the expression of genes related to angiogenesis, the inflammatory response, and cell proliferation was increased compared with the control. Compared with other storage media, the highest cell viability was observed in 50% HTK solution. CONCLUSIONS: Our study suggests that 50% HTK solution containing cell culture medium represents a suitable storage medium for avulsed teeth.


Assuntos
Soluções para Preservação de Órgãos , Avulsão Dentária , Glucose , Glutationa , Humanos , Insulina , Manitol , Preservação de Órgãos , Cloreto de Potássio , Procaína
11.
Life Sci ; 242: 117188, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31863772

RESUMO

AIMS: Reactive oxygen species (ROS) bidirectionally regulate insulin sensitivity in skeletal muscle. Insulin-induced ROS generation elevates insulin-regulated metabolic effects; however, chronic oxidative stress causes severe insulin resistance in skeletal muscle. Resveratrol (RV), as a natural antioxidant, eliminates intracellular ROS. It's unclear that whether it has different roles in insulin signaling pathway in skeletal muscle. MAIN METHODS: C57BL/6J mice and C2C12 myotubes were used to assess metabolic regulation effects of RV. Protein activation was detected using Immunofluorescence and Western Blot analysis. ROS were analyzed using confocal microscope and flow cytometry sorting (FACS). Intracellular reducing molecules were detected using an enzymatic method. Glucose uptake was measured using a fluorescent deoxyglucose analog (2-NBDG). KEY FINDINGS: We found that RV attenuated insulin-stimulated AKT phosphorylation via elimination of insulin-induced ROS generation in skeletal muscle, suggesting that RV decreased activation of the insulin-induced AKT signaling. In skeletal muscle of insulin resistance, RV reduced oxidative stress, restored intracellular glutathione (GSH) level, and enhanced insulin-induced AKT activation and glucose absorption. These results suggested that RV ameliorated insulin resistance by change of redox levels in skeletal muscle. SIGNIFICANCE: This study revealed bidirectional regulation effects of RV on insulin-stimulated metabolism in skeletal muscle through alternation of intracellular redox homeostasis, which might provide a guidance role for treatment of metabolic diseases.


Assuntos
Antioxidantes/farmacologia , Insulina/farmacologia , Músculo Esquelético/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Resveratrol/farmacologia , Animais , Western Blotting , Citometria de Fluxo , Imunofluorescência , Glutationa/metabolismo , Homeostase/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Músculo Esquelético/metabolismo , Espécies Reativas de Oxigênio/metabolismo
12.
Crit Rev Food Sci Nutr ; 60(2): 322-340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30463420

RESUMO

Diabetes, a metabolic syndrome of global importance has been on a progressive rise in recent years. Several pharmacological approaches have been made, which have proved effective, but with underlying side effects. Bioactive hydrolysates (BHs) and peptides (BPs) from food sources, however, have shown the relative advantage of imparting less adverse effects. Furthermore, BHs and BPs from food have been discovered to impart their antidiabetic potentials through one or more mechanisms such as inhibition of digestive enzymes, inhibition of the antigenic enzyme - Dipeptyl peptidase IV (DPP-IV), decrease in blood glucose levels and increase in insulin uptake. Several plants and animal sources have been used as protein sources for the isolation of antidiabetic hydrolysates and peptides through different mechanisms and analytical techniques. This review integrates recent research information about several popular and unconventional food sources of BHs and BPs, their isolation techniques, antidiabetic effects and protein profiles. In addition, the fractionation technique(s) employed in each study and inhibition potentials of BHs and BPs are reviewed. This article is intended to supplement accessible scholarly literature and intellectual awareness on the subject of food-oriented approach for the management of diabetes.


Assuntos
Inibidores da Dipeptidil Peptidase IV , Hipoglicemiantes , Animais , Alimentos , Insulina , Peptídeos , Hidrolisados de Proteína
13.
Biochem Med (Zagreb) ; 30(1): 010802, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31839727

RESUMO

Introduction: Hypoglycaemia has been reported as an unusual complication of tramadol use and in a few cases of tramadol poisoning, but the exact mechanism is not known. Case description: An ambulance crew was dispatched to an unconscious 46-year old man. A glucometer point-of-care measurement revealed a profound hypoglycaemia (1.9 mmol/L). Treatment with intravenous glucose was started and the patient was transported to the hospital. The patient had several episodes of pulseless electrical activity requiring cardiopulmonary resuscitation in the ambulance and upon arrival in the hospital. Despite continuous glucose infusion the hypoglycaemia was difficult to correct during the next few hours and the patient developed hypokalaemia. Further investigation to identify the cause of hypoglycaemia revealed that insulin and C-peptide were inappropriately raised. A toxicological investigation revealed the presence of tramadol and its metabolites in lethal concentrations. Also acetaminophen, ibuprofen and lormetazepam were present. Ethanol screening was negative (< 0.1 g/L) and no sulfonylurea were detected. The patient developed multiple organ failure, but eventually recovered. What happened: The hypoglycaemia was caused by inappropriate stimulation of insulin secretion in a patient intoxicated with tramadol. The sudden hypokalaemia was caused by a massive intracellular shift of potassium in response to the hyperinsulinemia, triggered by the intravenous administration of glucose. Main lesson: To our knowledge, we are the first to document a significant rise in endogenous insulin production in a hypoglycaemic patient presenting with tramadol intoxication. Our observation suggests that hyperinsulinemia could be the cause of the hypoglycaemia associated with tramadol use.


Assuntos
Analgésicos Opioides/efeitos adversos , Hipoglicemia/diagnóstico , Tramadol/efeitos adversos , Analgésicos Opioides/uso terapêutico , Glicemia/análise , Peptídeo C/sangue , Glucose/administração & dosagem , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/etiologia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Tramadol/uso terapêutico
14.
Gene ; 728: 144296, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31866555

RESUMO

Insulin and glucagon are important hormones for regulating blood glucose levels. Rodents are useful models for understanding human physiology, however, differences exist between rodents and humans. Here I examined the evolution of the genes encoding insulin (Ins) and glucagon (Gcg, which also encodes GLP-1 and GLP-2) and the receptors for these hormones (Insr, Gcgr, Glp1r, and Glp2r). Our results show that the insulin 1 gene (Ins1) that originated by retroposition in some rodents such as mice, experienced selective constraints that are as strong as those acting upon the Ins2 gene found in the locus-of-origin. Previous studies had shown that the insulin hormones and genes in hystricomorph rodents, such as the guinea pig, have altered function and selective constraints, respectively. Here I show that the insulin receptor genes in hystricomorph rodents also experienced changes in evolutionary rates, but that these changes did not alter sites involved in hormone binding. While glucagon, but not GLP-1 and GLP-2, in hystricomorph rodents also show increased rates of sequence evolution, no changes in the evolution of the glucagon receptor gene (Gcgr) was seen. Intriguingly, the GLP2 receptor gene (Glp2r) in mice-like rodents evolved more rapidly than those in hystricomorph rodents. When the rates of evolution of the genes encoding the receptors for proglucagon-derived peptides, which are all G-protein coupled receptors, were compared, the GLP-1 receptor gene (Glp1r) was found to display increased levels of sequence constraint compared to the Gcgr and Glp2r genes.


Assuntos
Evolução Molecular , Glucagon/genética , Insulina/genética , Receptor de Insulina/genética , Receptores de Glucagon/genética , Roedores/genética , Animais , Genoma , Filogenia
15.
J Sci Food Agric ; 100(2): 755-763, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31605375

RESUMO

BACKGROUND: ß-Hydroxy-ß-methylbutyrate (HMB) is the metabolite of leucine that plays an important role in muscle protein metabolism. The objective of the present study was to determine the effects of in ovo feeding (IOF) of HMB at 7 days of incubation (DOI) via air cell or 18 DOI via amnion on hatchability, muscle growth and performance in prenatal and posthatch broilers. RESULTS: IOF of HMB via air cell at 7 DOI increased hatchability by 4.34% compared with the control (89.67% versus 85.33%). Birds in IOF groups exhibited higher body weight, average daily body weight gain and pectoral muscle percentage. Furthermore, IOF of HMB significantly increased the level of plasma growth hormone, insulin and insulin-like growth factor-1. Chicks hatched from IOF treatment had larger diameters of muscle fiber and higher mitotic activity of satellite cells at early posthatch age. IOF of HMB activated satellite cells by upregulation of mRNA expression of myogenic transcription factors, myogenic differentiation one (MyoD) and myogenin. Chicks hatched from air cell injection group had higher pectoral muscle percentage at 5 d posthatch and greater satellite cell mitotic activity at 7 d posthatch than counterparts from amnion injection group. CONCLUSIONS: IOF of HMB via amnion at 18 DOI or especially via air cell at 7 DOI could be used as an effective approach to enhance hatchability, productive performance and breast muscle yield in broilers. © 2019 Society of Chemical Industry.


Assuntos
Galinhas/fisiologia , Músculos Peitorais/crescimento & desenvolvimento , Valeratos/metabolismo , Ração Animal/análise , Animais , Galinhas/sangue , Galinhas/genética , Galinhas/crescimento & desenvolvimento , Suplementos Nutricionais/análise , Comportamento Alimentar , Feminino , Hormônio do Crescimento/sangue , Insulina/sangue , Masculino , Mitose , Proteína MyoD/genética , Proteína MyoD/metabolismo , Mioblastos/citologia , Mioblastos/metabolismo , Miogenina/genética , Miogenina/metabolismo , Músculos Peitorais/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-31518684

RESUMO

Generally, fish are thought to have a limited ability to utilize carbohydrate. Postprandial blood glucose is cleared sluggishly in fish, resulting in prolonged hyperglycemia. Facilitative glucose transporters (GLUTs) play an important role in glucose utilization. In the present study, the expression levels of glut2 in different tissues were detected in grass carp. Furthermore, the effects of oral glucose administration on glut2 mRNA expression in the liver, intestine and kidney were investigated, and we also evaluated the response of glut2 mRNA to insulin and glucagon in the primary hepatocytes of grass carp. The expression level of glut2 mRNA was highest in the liver, followed by the intestine and kidney, but lower in other tissues. The result of glucose tolerance test (GTT) showed that serum glucose reached the highest level at 3 h after GTT and recovered to the basic level at 6 h. The glut2 mRNA in the intestine was up-regulated at 1 h after GTT. However, the glut2 mRNA expression in the liver of grass carp was unchanged after GTT for 1, 3, 6 h, and even decreased at 12 h after GTT. In addition, the expression of glut2 mRNA in the primary hepatocytes was enhanced by insulin and glucagon at 3 h post treatment. These results suggested that glut2 expression in the liver of grass carp was sensitive to insulin and glucagon, but not blood glucose. The up-regulation of glut2 by these hormones might be involved in the bi-directional transportation of glucose in the liver.


Assuntos
Cyprinidae/metabolismo , Proteínas de Peixes/metabolismo , Glucagon/metabolismo , Transportador de Glucose Tipo 2/biossíntese , Glucose/farmacologia , Hepatócitos/metabolismo , Insulina/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo
17.
Nat Med ; 25(12): 1865-1872, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792456

RESUMO

Viruses are implicated in autoimmune destruction of pancreatic islet ß cells, which results in insulin deficiency and type 1 diabetes (T1D)1-4. Certain enteroviruses can infect ß cells in vitro5, have been detected in the pancreatic islets of patients with T1D6 and have shown an association with T1D in meta-analyses4. However, establishing consistency in findings across studies has proven difficult. Obstacles to convincingly linking RNA viruses to islet autoimmunity may be attributed to rapid viral mutation rates, the cyclical periodicity of viruses7 and the selection of variants with altered pathogenicity and ability to spread in populations. ß cells strongly express cell-surface coxsackie and adenovirus receptor (CXADR) genes, which can facilitate enterovirus infection8. Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to ß cells between serotypes and within the same serotype9,10. In this large-scale study of known eukaryotic DNA and RNA viruses in stools from children, we evaluated fecally shed viruses in relation to islet autoimmunity and T1D. This study showed that prolonged enterovirus B rather than independent, short-duration enterovirus B infections may be involved in the development of islet autoimmunity, but not T1D, in some young children. Furthermore, we found that fewer early-life human mastadenovirus C infections, as well as CXADR rs6517774, independently correlated with islet autoimmunity.


Assuntos
Autoimunidade/imunologia , Diabetes Mellitus Tipo 1/virologia , Enterovirus/isolamento & purificação , RNA Viral/isolamento & purificação , Adolescente , Autoimunidade/genética , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Enterovirus/imunologia , Enterovirus/patogenicidade , Fezes/virologia , Feminino , Humanos , Lactente , Insulina/metabolismo , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/virologia , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/patologia , Ilhotas Pancreáticas/virologia , Masculino , Pâncreas/imunologia , Pâncreas/patologia , Pâncreas/virologia
18.
Anal Bioanal Chem ; 411(30): 8153-8162, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31797014

RESUMO

This work describes an analytical procedure based on automated affinity purification followed by liquid chromatography-electrospray tandem mass spectrometry with a conventional triple quadrupole analyzer, in order to detect synthetic insulins (Apidra®, Humalog®, Levemir®, NovoRapid®, and Tresiba®) in human urine. Sample preparation included ultrafiltration followed by immunoaffinity purification on monolithic microcolumns. Chromatographic separation was performed by a C18 microbore column, while mass spectrometric identification of the analytes was achieved by a triple quadrupole mass spectrometer under positive ion electrospray ionization and acquisition mode in selected reaction monitoring. Identification of the synthetic insulins was performed by selecting at least two characteristic ion transitions for each analyte. The newly developed method was validated in terms of specificity, recovery, matrix effect, sensitivity, robustness, and repeatability of retention times and relative ion transition abundance. The specificity and the reproducibility of the relative retention times and the relative abundance of the characteristic ion transitions selected was confirmed to be fit for purposes of ensuring the unambiguous identification of all target analytes, also in the forensic field. The extraction yield was estimated at greater than 60% and the matrix effect smaller than 35%. The lower limits of detection were in the range of 0.02-0.05 ng/mL, proving the method to be sufficiently sensitive to detect the abuse of insulins in cases where they are used as performance-enhancing agents in sport. The applicability of the developed method was assessed by the analysis of urine samples obtained from diabetic subjects treated with Tresiba® and/or Humalog®, whose presence was confirmed in urine samples collected after the administration of therapeutic doses. Graphical abstract A hybrid assay comprising MSIA-based immunoextraction combined with liquid chromatography-electrospray tandem mass spectrometry was developed and validated for the detection of recombinant insulins in human urine.


Assuntos
Cromatografia de Afinidade/métodos , Cromatografia Líquida/métodos , Insulina/urina , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia de Afinidade/instrumentação , Humanos , Limite de Detecção , Proteínas Recombinantes/urina , Reprodutibilidade dos Testes
19.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4158-4164, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872693

RESUMO

Insulin resistance,as the main link in the pathogenesis of type 2 diabetes mellitus( T2 DM),runs through the whole process of occurrence and development of T2 DM and is closely related to the insulin receptor signaling pathway. Insulin stimulation causes autophosphorylation of the insulin receptor( IR),which then activates tyrosine phosphorylation of insulin receptor substrate( IRS).Phosphorylation of IRS can induce and activate phosphatidylinositol 3-kinase( PI3 K),subsequently activate downstream 3-phosphoinositide-dependent protease 1( PDK1) and Akt/PKB,and finally promote expression and translocation of glucose transporter 4 to increase glucose uptake of insulin-sensitive tissues and alleviate insulin resistance. Currently,oral hypoglycemic agents for clinical treatment of T2 DM have different side effects on the human body. Traditional Chinese medicine not only has a wide range of sources and abundant types,but also has comprehensive multi-component,multi-link and multi-target effects,showing unique advantages in the treatment of diabetes. In recent years,more and more researchers at home and abroad pay attention to the active ingredients in traditional Chinese medicine for alleviating insulin resistance. In this paper,we would summarize the active hypoglycemic ingredients of traditional Chinese medicine associated with the insulin receptor signaling pathway,which may provide some theoretical guidance for the development of traditional Chinese medicine in the treatment of diabetes.


Assuntos
Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Medicina Tradicional Chinesa , Receptor de Insulina/metabolismo , Diabetes Mellitus Tipo 2 , Humanos , Insulina , Proteínas Substratos do Receptor de Insulina , Fosfatidilinositol 3-Quinases , Fosforilação , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais
20.
Medicine (Baltimore) ; 98(50): e18346, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852132

RESUMO

BACKGROUND: Type 2 diabetes (T2D) is a significant health concern worldwide, and good glycemic control is the basis of avoiding disease progression. Herbal tea, as a convenient and effective medication method, has gained popularity among many diabetic patients. However, there are no systematic reviews or meta-analyses to evaluate the clinical efficacy of herbal tea on T2D. METHODS: Four English electronic databases and 4 Chinese electronic databases were searched for randomized controlled trials (RCTs) meeting inclusion criteria; Clinical trials were searched to explore the relevant unpublished data. Fasting blood glucose and glycated hemoglobin will be measured as primary outcomes. Secondary outcomes include 2-hour postprandial blood glucose, fasting insulin, and homeostasis model assessment-insulin resistance. The heterogeneity of data will be investigated by Chi-square and I test; subgroup analysis and sensitivity analysis will be conducted to explore the sources of heterogeneity; funnel plot will be used to evaluate publication bias; finally, we will use grading of recommendations assessment, development, and evaluate system method to evaluate the quality of evidence. Merging analysis of data will be performed using Rev Man 5.3 software. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSIONS: The systematic review will confirm whether herbal tea consumption is benefit to the glycemic control in patients with T2D. PROSPERO REGISTRATION NUMBER: CRD42019129863.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Índice Glicêmico , Chás de Ervas , Diabetes Mellitus Tipo 2/dietoterapia , Jejum , Hemoglobina A Glicada/análise , Humanos , Insulina/sangue , Resistência à Insulina , Metanálise como Assunto , Projetos de Pesquisa , Revisão Sistemática como Assunto
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