Obesidade, inflamação e complicações metabólicas / Obesity, inflammation and metabolic complications

The prevalence of obesity has increased in the past two decades. This growth has been attributed to changes in dietary habits, especially increased consumption of fats and sugars. It is clear that obesity is a risk factor for cardiovascular disease and insulin resistance, and the inflammatory process favors this context. Aim: To address the inflammatory aspects of obesity and associated metabolic complications. Data Sources: Original data from articles found through search of scientific databases. Summary of findings: Micro hypoxia, reticulum stress, and activation of toll-like receptor 4 are responsible for triggering inflammation in adipose tissue, which is the place where the process begins. Thus, there is an increased production of various adipokines, such as IL-6 and TNF-?, which impair insulin signaling pathway, leading to resistance to hormone, one of the first complications of obesity. From this, with the intensity of stimulation, the condition may worsen triggering type 2 diabetes and other comorbidities. Conclusion: Thus, the elucidation of the roles and mechanisms of the main adipokines lead to a better understanding of the pathogenesis of obesityrelated disorders.

A prevalência da obesidade tem aumentado durante as duas últimas décadas. Esse crescimento tem sido atribuído a mudanças no hábito dietético, principalmente maior consumo de gorduras e açúcares. É evidente que a obesidade é um fator de risco para doenças cardiovasculares e resistência insulínica, e o processo inflamatório favorece esse contexto. Objetivo: Abordar os aspectos inflamatórios da obesidade e as complicações metabólicas associadas. Fonte de dados: Artigos levantados por meio de pesquisa em base de dados. Síntese dos dados: A microhipóxia, o estressedo retículo e a ativação dos receptores toll-like 4 são responsáveis por desencadear a inflamação no tecido adiposo, sendo esse o local onde se inicia o processo. Dessa forma, há um aumento na produção de diversas adipocinas, como IL-6 e TNF-?, as quais prejudicam a via de sinalização da insulina, levando à resistência a esse hormônio, uma das primeiras complicações da obesidade. A partir disso, com a intensidade desse estímulo, o quadro pode agravar-se, desencadeando diabetes melito tipo 2 e outras comorbidades. Conclusão: Assim, a elucidação das funções e mecanismos de ação das principais adipocinas levará a uma melhor compreensão da patogênese de desordens ligadas à obesidade.

Dietary fiber psyllium based hydrogels for use in insulin delivery

The present article is related to the development of psyllium based oral insulin delivery systems that could release insulin in a controlled and sustained manner. Psyllium is a medicinally important gel, forming glucoe lowering dietary fiber and drug delivery system developed by its functionalization will have the double potential of curing diabetes. Psyllium and acrylamide/methacrylamide based hydrogels were prepared, and the effect of pH on the release dynamics of insulin from drug loaded hydrogels has been studied to evaluate the drug release mechanism. Non-Fickian diffusion mechanism has been observed for the release of insulin in the pH 7.4 buffer

[Pharmacokinetic comparison between regular insulin and oral insulin based on superporous hydrogel polymers in healthy volunteers]

All contemporary methods of insulin administration are non-physiological. Insulin is not absorbed from the gastrointestinal tract because of its peptide nature. The aim of the present study was to examine the absorption of oral insulin from gastrointestinal tract, using novel oral formulation- adding a delivery agent superporouse hydrogel [SPH] and SPH composite [SPHC] in combination with insulin. Capsules containing insulin and SPH and SPHC were administered orally, to 15 non-diabetic subjects in order to assess its biological effects and safety. Plasma glucose, insulin and c - peptide serum levels were determined, at timed intervals up to 4 h. In the present study, we showed that AUC of exogenous insulin in polymer -insulin group was higher than sub-cutaneous regular insulin group. It means that addition of SPHC polymer caused increase in insulin absorbtion.In addition, Insulin Tmax in polymer group was longer than sub-cotaneaus insulin group. Blood glucose AUC in sub-cotaneaus group was higher than polymer group.AUC C-peptide serum level in polymer group was higher than sub-cutaneous group. Insulin in combination with a novel delivery agent, SPH and SPHC, given orally is absorbed through the GI tract in a biologically active form. This was demonstrated by suppression of endogenous insulin secretion

Insulin adsorbance to polyvinylchloride [PVC] surfaces of Fluid container and infusion - set

In total parenteral nutrition [TPN] solution, adsorbance of insulin to polyvinylchloride [PVC] surfaces of fluid containers and infusion-sets, decrease the amount of insulin that reaches the patients. To clarify the binding sites of insulin and to propose a solution to overcome this problem. To each of four 1000ml. PVC bottles of 5% dextrose solution, 300 microunit of insulin per each milliliter of dextrose solution were added. Each bottle was then connected to an infusion-set and the system made to run at an infusion rate of 100 ml. per hour. One milliliter samples were then collected from both the PVC bottles and infusion-sets-terminal, separately, immediately at the starting point [time zero] and 15, 30, 45 and 60 minutes thereafter. The concentrations of insulin were checked using insulin kits. At the starting point [time zero] the mean of insulin concentrations among four PVC bottles was 213.79 microunit per each milliliter of 5% dextrose solution. No significant fluctuation was noted in the concentration of insulin in the PVC bottles through 60 thminute period. However the concentration of insulin at infusion-set- terminal decreased significantly at the end of the same hour [p value=0.004]. Our results demonstrate that the adsorbance of insulin takes place at the surfaces of infusion sets. It follows therefore that increase in the primary dosage of insulin added to PVC infusion solutions and the selection of a suitable infusion set [polyethylene] seem to be beneficial for overcoming this problem

Fatores hepatotróficos e regeneraçäo hepática. Parte I: o papel dos hormônios / Hepatotrophic factors and liver regeneration. Part I: the role of hormones

No complexo processo de proliferaçäo celular, os hormônios agem de diferentes maneiras ao atingirem seus receptores nos tecidos-alvo. Os principais fatores ligados ao crescimento hepático säo HGF, TGF-alpha, IL-6, TNF-alpha, norepinefrina, EGF e insulina. O GH estimula tanto o fígado a produzir fatores de crescimento, como a expressäo genética do HGF e a síntese de DNA. Hormônios tireoideanos aumentam a capacidade proliferativa dos hepatócitos. A insulina age sinergicamente com GH e glucagon. Näo tem potencial mitogênico primário mas intensifica o estímulo regenerativo iniciado pela epinefrina e norepinefrina. Esta amplifica os sinais mitogênicos do EGF e HGF, induz a secreçäo de EGF e antagoniza os efeitos inibitórios do TGF-beta 1. O glucagon isoladamente näo produz efeitos mas provavelmente participa na síntese de DNA e da resposta homeostásica pela qual a glicemia é mantida estável durante a regeneraçäo. Também há indícios de açäo hepatotrófica da gastrina.

Pharmacokinetic study of niosome encapsulated insulin.

Pharmacokinetic profile and hypoglycemic effect, after intraperitoneal injection of insulin and insulin encapsulated in niosomes were determined in diabetic rats. Niosomes (non-ionic surfactant vesicles) of different doses and different lipid compositions were prepared by lipid layer hydration method. Plasma samples were collected at specified time intervals and plasma concentration of insulin was determined by HPLC. Blood glucose level was estimated spectrophotometrically using commercial glucose assay kit. In vitro release and pharmacokinetic profile of niosomal formulation and free insulin were evaluated. Though there was a slight delay in the in vitro drug release due to cholesterol content in the niosomes, there was no difference between the two preparations when plasma levels were compared in vivo. Niosomes significantly reduced the blood glucose level in diabetic rats. Fall in blood glucose level was almost 92% of initial value. In case of the niosomal form the half-life of insulin was prolonged by 4 -5 hr in contrast to 2 hr for free drug. Niosomes maintained the plasma insulin level up to 12 hr, but free drug was cleared quickly. The area under the plasma concentration-time curve for niosomal forms was, 26.07 degrees +/- 0.99 mIU. hr/ml and for free insulin was 11.722 +/- 1.00 mIU. hr/ml. More than 80% of the drug was successfully encapsulated to give a formulation with sustained release characteristics. Entrapment efficiency increased with increasing lipid concentration and decreased with increasing drug concentration. The results showed that insulin entrapped in niosomes prolongs the existence of drug in the body therefore increasing its therapeutic value.

Bronchopulmonary absorption of aerosolised insulin.

Seven non-insulin dependent diabetes mellitus (NIDDM) patients aged 48 to 78 years, inhaled approximately 10 to 20 units of aerosolised insulin (human actrapid) by nebuliser. In 5 cases, approximately 10 units of insulin aerosol inhalation was given 4 hours after breakfast. Blood glucose level started falling after 15 minutes with a maximum fall at 45 minutes to 1 hour. In 2 cases insulin aerosol inhalation was given 2 hours after lunch. The first dose of 10 units of insulin did not show any significant change in blood glucose level at 30 minutes. A second dose of 10 units of insulin aerosol was inhaled after 30 minutes and blood glucose level started falling in a pattern similar to the first group of patients. The first dose appears to withhold the rise of blood glucose in the postprandial phase and the second dose lowers the blood glucose level. The result is compared with placebo inhalation and there is a significant fall of blood glucose level with insulin aerosol inhalation. It admits of little doubt that insulin is absorbed from the bronchopulmonary mucosa.

Gastric emptying in insulin treated diabetics, a new equation for insulin meal interval

Gastric emptying time was studied in 25 insulin-treated diabetics, compared with 12 matched healthy volunteers. Both liquid and solid meals labeled by technetium sulfur-colloid [99m Tc] as the isotopic marker were used. The results showed delayed gastric emptying time in the diabetic group for liquid [0: 45 +/- 14 min.] and solids [1: 20 +/- 38 min.] compared with [0: 31 +/- 10 and 0: 49 +/- 0: 15 min.] in the control group [P = 0.04 and 0.008, respectively]. The delay in the diabetic group was apparent in males, older age and with longer duration of diabetes, and also in those who had gastrointestinal symptoms, peripheral or autonomic neuropathy. Adjusting the time of insulin injection in relation to the times of meals according to the solid-lag time by applying the equation [the onset of insulin action-solid lag time] caused significant reduction in fasting and post-prandial blood glucose level resulting in a better glycemic control

Estudo da dinâmica insulínica e da secreçäo de cortisol em pacientes com deficiência de glicose-6-fosfato desidrogenase / Insulin dinamic and cortisol secretion study in patients with glicose-6-phosphate dehydrogenase deficiency

Na presente pesquisa, o objetivo foi avaliar de forma mais precisa a secreçäo da insulina através da quantificaçäo do peptideo C plasmático após estímulo glicídico, assim como, após a L-arginina, outro estimulante da secreçäo de insulina, além da sensibilidade periférica à insulina. Constou dos objetivos avaliar a secreçäo de cortisol após estímulo com ACTH. Para tanto, foram estudados 11 indivíduos com deficiência de G-6-PD e 11 indivíduos controle que formaram o grupo I e foram submetidos aos testes para avaliar a funçäo secretória da célula pancreática (teste endovenoso de tolerância à glicose - TETG e teste de arginina) e a sensibilidade periférica à insulina (teste de tolerância à insulina - TTI). E, o grupo II composto com 12 indivíduos com deficiência de G-6-PD e 16 indivíduos com deficiência de G-6-PD e 16 indivíduos controle que foram submetidos à estimulaçäo das adrenais com ACTH (Teste de cortisol). Para os dois grupos de estudo os procedimentos experimentais foram realizados após jejum de 12-14 h. Os resultados demonstram que pacientes com deficiência de G-6-PD apresentam diminuiçäo na secreçäo de insulina (fase rápida) após estímulo com glicose e L-arginina, sensibilidade periférica à insulina semelhante a de indivíduos controle e secreçäo de cortisol diminuida durante a primeira hora após estimulaçäo com ACTH

Estudio comparativo de insulina y gliburida contra gliburida o insulina, en control crónico de pacientes con diabetes tipo II / Comparative study of insuline and gilburide or insuline for the chronic control of type II diabetic patients

Con el fin de conocer la utilidad de un tratamiento combinado con gliburida e insulina NPH se estudiaron 25 pacientes con diabetes mellitus tipo II controlados. Se ordenaron al azar en tres grupos: Grupo I, recibieron solamente gliburida; Grupo II tratados con insulina únicamente; Grupo III se les administró gliburida e insulina. Se determinaron niveles de glucosa en ayuno, hemoglobina glucosilada y péptico C durante cinco meses. Se realizó análisis de varianza para el procesamiento estadístico de los datos. La determinación inicial y final de la glucosa fue: Gupo I: 169.3 mg por ciento y 139.0 mg por ciento respectivamente (p > 0.05); Grupo II: 202.1 mg por ciento (p > 0.05); Grupo III: 157.8 mg por ciento (P > 0.1). Para la hemoglobina glucosilada el Grupo I: 7.2 por ciento y 5.1 por ciento (p > 0.05), Grupo II: 6.2 por ciento y 5.1 por ciento (p > 0.05) y Grupo III: 5.7 por ciento y 4.7 por ciento (p > 0.05). El péptido C registró 2.5 y 4.5 en el Grupo I: (p > 0.05) Grupo II: 2 y 4.1 (p > 0.05) y Grupo III: 3.2 y 5.3 (p > 0.05), y no se obtuvo diferencia estadística significativa en los datos. Se concluye que el tratamiento combinado demostró ser efectivo, pero no superior, para controlar al paciente diabético y puede ser una alternativa terapéutica útil en pacientes bien seleccionados

Prolonged effect and efficacy of a new double layered insulin suppository in patients with IDDM

A new double layered insulin suppository was formulated in order to prolong the effect of bioavailable insulin in treating insulin dependent diabetic subjects. The enhancement of the bioavailability was also possible through the use of a new enamine derivative as a promoter. A 300 U insulin suppository [total mean 4.2 U/Kg] with biphasic insulin release action had a prolonged effect of up to 7 hours with smooth decrease of blood sugar. The insulin response after suppository administration demonstrated a significant positive correlation [r= 0.919, P< 0.001] with the plasma glucose level before administration

Effects of fatty ethers and stearic acid on the gastrointesinal absorption of insulin

Cuando se administra insulina a un animal atavés de la vía oral esta es inmediatamente degradada. El propósito de este trabajo es estudiar la efectividad de los compuestos que se indican a continuación para aumentar la absorción de insulina, estos son los siguientes: polietileno (20) cetil éter (Brij 58), polietileno (20) oleil éter (Brij 99) y polietileno lauril éter. Estos compuestos además de ácido esteárico se usaron para preparar gránulos con o sin insulina y fueron administrados oralmente a conejos. A estos animales se les midieron los niveles de glucosa e insulina a diferentes intérvalos de tiempo antes y después de la administración oral de los gránulos.l Se uso un glucómetro y el método de radioinmunoensayo (RIA) para hacer las respectivas medidas. Con el propósito de determinar si hay relación entre los niveles de glucosa e insulina en la sangre se uso el método de radioinmunoensayo por ser un método muy sensitivo que puede detectar pequeños cambios en la concentración de insulina en la sangre. Se observó un raducción significativa en los niveles de glucosa (P<0.05) después de administrarlos los gránulos. En otro experimento se inyectó 1/5 parte de la dósis oral de insulina y se observó una respuesta similar. Sin embargo, sólo los gránulos preparados con Brij 58, que contenían insulina produjeron altos niveles de insulina en la sangre. Esto fue equivalente a 1/10 del cambio producido por la inyección subcutánea de la hormona. En estos experimentos los cambios en insulina ...

Contribución experimental al conocimiento del mecanismo de acción de la digital / Experimental contribution of the knowledge of mechanism action of the digitalis

Trabajos iniciales de 1949 usando corazones aislados de sapo en tercera fase nicotínica, mostraron la acción inotrópica positiva de los digitálicos, en este caso la ouabaina, lo cual demuestra que la acción de este fármaco se ejerce sin intervención del sistema nervioso. En 1982 se demostró la necesidad de la presencia de iones Ca + + en el líquido de perfusión de la piel de sapo, para que se produjera la acción de la insulina. Luego se vio el efecto de estos iones como potenciadores de la insulina en el bioensayo de las convulsiones del ratón y en el de la acción hipoglucemiante en el conejo. Estos estudios condujeron a pensar que la insulina actuaba sobre una ATPasa de transporte calcio-dependiente, similar a aquella sobre la cual actúa la digital y que por tanto los digitálicos debían tener un efecto insulínico similar. Se demostró que la ouabaina aumenta el consumo de glucosa por la célula, tanto en el bioensayo del ratón. como en la grasa epididimaria y que tenía un efecto insulímico de alrededor de 11 U de insulina por 1 mg. Otros estudios demostraron que la insulina tiene un efecto inotrópico similar a la digital sobre la aurícul; a aislada de rata y que este efecto se ejerce en forma dosis-efecto, lo cual indica que existen receptores para esta acción a nivel de la fibra cardiaca, lo mismo que para la digital. La glucosa también ejerce acción inotrópica, tipo dosis-efecto, pero a concentraciones muy elevadas, imposibles de obtener en el organismo entero, Otras hexosas son agonistas parciales de la glucosa. Sin embargo, ni el efecto de los digitálicos, ni el de la insulina, se ejercen a través del metabolismo..