Alterations of epinephrine-induced gluconeogenesis in aging

The effects of glucagon and epinephrine on gluconeogenesis in young (4 month) and old (24 month) Fisher 344 rat hepatocytes were compared. In contrast to glucagon, which had a similar effect on gluconeogenesis in both young and old cells, epinephrine caused a smaller increase in gluconeogenesis in old rat hepatocytes than in young hepatocytes. beta2 adrenergic receptor (beta2-AR) expression slightly decreased in aged rat liver, and there were differences between young and old hepatocytes in their patterns of G protein coupled receptor kinases, which are involved in the activation of beta2-AR receptor signal desensitization. The major isoform of the kinase changed from GRK2 to GRK3 and the expression of beta-arrestin, which is recruited by the phosphorylated beta2-AR for internalization and degradation, increased in aged rat liver. GRK3 overexpression also decreased the glucose output from young rat hepatocytes. We conclude that an age-associated reduction in epinephrine-induced gluconeogenesis occurs through the epinephrine receptor desensitizing system.

Alterations of epinephrine-induced gluconeogenesis in aging

The effects of glucagon and epinephrine on gluconeogenesis in young (4 month) and old (24 month) Fisher 344 rat hepatocytes were compared. In contrast to glucagon, which had a similar effect on gluconeogenesis in both young and old cells, epinephrine caused a smaller increase in gluconeogenesis in old rat hepatocytes than in young hepatocytes. beta2 adrenergic receptor (beta2-AR) expression slightly decreased in aged rat liver, and there were differences between young and old hepatocytes in their patterns of G protein coupled receptor kinases, which are involved in the activation of beta2-AR receptor signal desensitization. The major isoform of the kinase changed from GRK2 to GRK3 and the expression of beta-arrestin, which is recruited by the phosphorylated beta2-AR for internalization and degradation, increased in aged rat liver. GRK3 overexpression also decreased the glucose output from young rat hepatocytes. We conclude that an age-associated reduction in epinephrine-induced gluconeogenesis occurs through the epinephrine receptor desensitizing system.

Efecto de la administración de triiodotironina y glucagón sobre la expresión hepática del receptor de lipoproteínas de alta densidad y el metabolismo del colesterol en el ratón / Effect of triiodothyronine (T3) and glucagon on hepatic expression of SR-BI and lipoprotein cholesterol metabolism in mice

Introducción: El receptor scavenger clase B tipo I (SR-BI) es un elemento clave en el metabolismo de las HDL, donde su expresión ejerce un importante efecto anti-aterogénico controlando la fase hepática del transporte reverso de colesterol. Así, el estudio de la modulación de la expresión de SR-BI permitiría el desarrollo de nuevas alternativas farmacológicas para el tratamiento de la ateroesclerosis. Objetivo: La meta de nuestro estudio fue determinar el efecto de la triiodotironina (T3) y el glucagón sobre el metabolismo del colesterol HDL y la expresión hepática de SR-BI en el ratón, evaluando simultáneamente su impacto sobre el colesterol total y lipoproteico plasmático y la secreción biliar de colesterol. Métodos: Se utilizaron ratones C57BL/6 tratados con T3 (30 nmol/kg/día) o glucagón (80 µg/día) más los respectivos grupos controles. Después del tratamiento, los animales se anestesiaron para recolección de bilis, plasma y tejido hepático. Los niveles totales de colesterol plasmático y biliar fueron medidos por métodos enzimáticos. El colesterol lipoproteico plasmático se evaluó por fraccionamiento cromatográfico del plasma y medición enzimática del colesterol en cada fracción. La expresión hepática de SR-BI se cuantificó mediante western blot. Resultados: El uso de T3 o glucagón disminuyeron significativamente el colesterol plasmático total y aumentaron el colesterol biliar con respecto al grupo control correspondiente. Las fracciones de colesterol VLDL, LDL y HDL disminuyeron en ambos grupos tratados, con un mayor efecto observado en la fracción HDL. La administración de ambas hormonas aumentaron significativamente los niveles hepáticos de SR-BI. Conclusión: Los resultados establecen que T3 y glucagón disminuyen el colesterol plasmático, predominantemente de tipo HDL, y aumentan la secreción de colesterol biliar en el ratón, probablemente como consecuencia del incremento en la expresión hepática...

Introduction: The scavenger receptor class B type I (SR-BI) plays a key role in the metabolism of high-density lipoprotein (HDL) cholesterol. Its expression has an important anti-atherogenic effect by controlling the hepatic phase of the reverse cholesterol transport pathway in vivo. Thus, the study of the modulation of SR-BI expression may allow the development of new pharmacologic approaches for treatment of atherosclerotic cardiovascular disease. Objective: The goal of this study was to determine the effect of triiodothyronine (T3) and glucagon on HDL metabolism and hepatic expression of SR-BI in mice, evaluating also the impact in total and lipoprotein cholesterol as well as biliary cholesterol secretion. Methods: C57BL/6 mice were treated with T3 (30 nmol/kg/día) or glucagon (80 µg/día) in comparison to appropriate control groups. After treatment, bile, plasma and hepatic tissue were collected for analysis. Total plasma and biliary cholesterol levels were measured by enzymatic methods. Lipoprotein cholesterol was also measured enzymatically after chromatographic separation of plasma samples. The hepatic expression of SR-BI protein was quantified by western blotting. Results: The use of T3 or glucagon significantly decreased total plasma cholesterol levels and increased of biliary cholesterol concentrations compared to control groups. Levels of VLDL, LDL and HDL cholesterol were reduced in both treatment groups, with a more important effect observed in the HDL fraction. Both treatments increased hepatic SR-BI protein levels. Conclusions: These results show that T3 and glucagon decrease plasma cholesterol levels, particularly in HDL, and increase biliary cholesterol secretion in mice, probably as a consecuence of higher hepatic expression of SR-BI, which may have led to facilitated HDL cholesterol transport from plasma into bile.

Papel de los mediadores vasoactivos en la fisiopatología de la hipertensión portal / Role of vasoactive mediators in the physiopathology of portal hypertension

Se evalúa el papel de los mediadores vasoactivos en la fisiopatología de la hipertensión portal, ya sea promoviendo un aumento de la resistencia vascular en la circulación intrahepática y/o portocolateral, o estimulando una vasodilatación esplácnica con un paralelo incremento del flujo sanguíneo portocolateral. En la actualidad se conoce que el factor inicial de la hipertensión portal es el aumento de la resistencia vascular intrahepática, ocasionada por los cambios morfológicos del hígado asociados a la cirrosis. Sin embargo, existen en la actualidad múltiples evidencias sobre la participación de un componente activo, células con propiedades contráctiles, que puede ser modulado por mediadores vasoactivos como la endotelina y el óxido nítrico. Por otra parte, se conoce actualmente que el aumento del flujo sanguíneo portal mantiene y agrava el síndrome de hipertensión portal. Este aumento del flujo portal es el resultado de una vasodilatación esplácnica ocasionada tanto por el aumento de sustancias vasodilatadoras como por una hiporreactividad a vasoconstrictores endógenos. En este sentido, estudios clínicos y experimentales han demostrado que sustancias como el glucagon, la prostaciclina y más recientemente el óxido nítrico, pueden jugar un papel importante en ambos mecanismos de vasodilatación esplácnica

Histologic and quantitative studies on the augmentation of liver regeneration with glucagon following partial hepatectomy in the rat

The effect of glucagon on the augmentation of liver regeneration following partial hepatectomy of the rat was investigated. Then was a significant increase in the weight of the liver both at day 3 [P<0.01] and day 7 [P<0.001] after partial hepatectomy and the start of glucagon treatment Mitotic Index showed a significant increase [P<0.001] in both partial hepatectomy group [group II] and partial hepatectomy and glucagon treated group [group III]. Stem cells were seen in the portal tract in the vicinity of bile ducts. The great majority of mitotic figures were seen in the prophase stage and were located in zone I of the liver acinus. An increase in ribosomes and mitochondrial number were observed specially in zone I of the liver acinus

Eritema necrolítico migratorio: presentación de un caso y revisión de la literatura / Necrolytic migratory erythema: case and literature review

El eritema necrolítico migratorio es una erupción cutánea característica, con hallazgos histopatológicos específicos que se relacionan frecuentemente con un tumor pancreático, el glucagonoma. Los pacientes con este síndrome son generalmente mal diagnosticados. Se presenta un paciente de 54 años de edad con una erupción cutánea recurrente, pérdida de peso, glositis e hiperglucemia de cuatro meses de duración. Esta importante, pero rara enfermedad, puede ser diagnosticada tempranamente, basándonos en el cuadro cutáneo

Significance of changes of serum bile a cid level after glucagon injection in patients with liver cirrhosis

In this study, the fasting serum total bile acid level and 15, 60 and 120 minutes levels after intravenous administration of 1 mg glucagon were measured in 34 cirrhotic patients [divided into grades A, B and C according to child's classification] and 10 apparently healthy individuals as a control group. The fasting total bile acid [TBA] level was significantly high in all patients as compared with the control group [p <0.001]. From the results it was found that glucagon induced reduction in serum TBA level mostly in the cases with relatively low grade severity of liver cirrhosis, whereas the majority of severe cases showed an increase. This reduction of serum TBA is due to enhancement of Na +/- coupled membrane transport of bile acids in hepatocytes under effect of glucagon. Lack of this response may be indicative of cell membrane dysfunction in the liver. So, glucagon- induced alteration of serum TBA level is non invasive technique which could be a useful liver function test that is correlated with the severity of liver cirrhosis

Stimulation of intact rat liver by exogenous hepatotrophic factors with additional growth of its mass

It was previously demonstrated that it is possible to increase the size of the intact liver of rats, contray to the biological determination that ties liver size to animal size bay intraperitoneal (portal) administration of exogenous hepatotrophic factors (a solution containing glucose, amino acids, insulin, glucagon, vitamins, and electrolytes) which qualitatively mimie substances and hormones normally present in splanchnic blood (PARRA et al.). In the present investigation, we studied the possible action of fat (LipofundinR), human milk growth factors, co-factors (folic acid, vitamin B12 and zinc), and thyroid hormone (T3 on the regenerative stimulus when added to the above solution. T3 was found to be an important factor which increased liver mass when compared to the basic solution (67.54 por cento) versus 36.07 por cento). Although these values were not compared statistically due to the small number of surviving animals, they are important as guidelines for future research about new compositions of hepatotrophic solutions that will maintain or improve the level of stimulation obtained thus far, with a possible reduction in animal mortality

Natriuretic effect of glucagon in starved and fed rats

The study was carried out on 40 male albino rats [a fed group and a starved group]. Half of the animals in each group received intravenous injection [1.5 ng/g b. wt.] for 4 consecutive days. Glucagon treatment prevented starvation induced sodium retention and was observed to enhance the glomerular filtration rate [GER] and to lack an influence on the renal Na+ - K+ ATPase enzyme. So, it can be concluded that the natriuretic action of glucagon can be considered to be performed at the glomerular level

Regeneraçäo do fígado intacto de ratos com crescimento adicional de sua massa, estimulado por fatores hepatotróficos exógenos / Intact liver regeneration of rats with additional growth of its mass, stimulated by exogenous hepatotrophic factors

Foi anteriormente demonstrado em ratos que é possível aumentar o tamanho do fígado intacto, contrariando determinaçäo biológica que o vincula ao porte do animal, com a administraçäo intraperitoneal (portal) de fatores hepatotróficos exógenos (soluçäo de glicose, aminoácidos, insulina, glucagon, vitaminas e eletrólitos) que mimetizam, em qualidade, substâncias e hormônios normalmente existentes no sangue esplâncnico (PARRA e col.) Neste trabalho estuda-se a possível açäo, sobre o estímulo regenerativo, de gordura (Lipofundin, fatores de crescimento do leite humano, co-fatores (ácido fólico, vitamina B12 e zinco) e hormônio tiroideano (T3), quando adicionados à soluçäo anterior. Verificou-se que o T3 é fator importante, tendo aumentado a massa hepática em relaçäo à soluçäo basal (67,54// versus 36,07//). Embora tais valores näo tenham sido comparados estatísticamente pelo reduzido número de animais sobreviventes, säo todavia importantes para orientar futura pesquisa que vise buscar nova composiçäo para a soluçäo de fatores hepatotróficos que mantenha ou melhore o nível de estímulo já conseguido com possível reduçäo na mortalidade dos animais

In vitro influence of hormones on transport of glucose and glycogen in liver and muscle of pinealectomised pigeons, Columba livia Gmellin.

To substantiate the increased peripheral utilization of blood glucose by pineal in wild pigeons, an in vitro study on the ability of liver and muscle slices of intact and pinealectomised wild pigeons (C. livia) in terms of uptake and release of glucose, and deposition and depletion of glycogen, in presence of insulin, acetylcholine, glucagon and adrenaline has been undertaken. A total insensitivity of liver and muscle of pinealectomised birds for glycogen deposition and insensitivity of liver for glucose uptake has been observed. Increased glucose release from liver in response to adrenalin has been observed. The results are discussed in terms of involvement of pineal in metabolic regulation associated with breeding activities.

Effect of adrenalectomy on fast-induced lipolysis in the chicken adipose tissue

O efeito da adrenalectomia sobre a lipólise induzida pelojejum, em tecido adiposo de frangos, foi estudado in vitro. Embora a liberaçäo de ácidos graxos livres näo tenha sido alterado pela adrenalectomia, houve uma significante queda na liberaçäo de glicerol para o meio de incubaçäo, indicando uma menor resposta lipolítica do tecido adiposo. Por outro lado, a epinefrina e a insulina näo apresentaram efeito tanto sobre o tecido adiposo das aves adrenalectomizadas quanto dos seus controles, e o marcado efeito lipolítico do glucagon näo foi afetado pela adrenalectomia. Esses resultados sugerem que, em frangos, osglicocorticóides adrenais säo requeridos para resposta lipolítica induzida pelo jejum

Efeito de estímulos fisiológicos sobre a motricidade do esfíncter de Oddi / Effect of physiological stimuli on the Oddi's sphincter motility

A atividade mioelétrica do esfíncter de Oddi foi avaliada tanto nos estados de jejum, como prandial e após a administraçäo de hormônios gastrointestinais que podem desempenhar uma importante funçäo no controle da motricidade do esfíncter de Oddi. A eletromiografia do esfíncter de Oddi e do trato gastrointestinal foi realizada em 21 opossums em jejum e após a administraçäo de 20 Cal/kg de lipídios, proteínas, carboidratos ou de uma mistura isocalórica desses três alimentos. O efeito de hormônios gastrointestinais (colecistoquinina, gastrina, glucagon e secretina) também foi estudado. O segmento proximal do esfíncter de Oddi gerou potenciais de açäo espontâneos que se propagaram para o segmento distal do esfíncter. O esfíncter de Oddi apresenta uma variaçäo na freqüência dos potenciais de açäo durante o jejum que se correlaciona com a atividade mioelétrica do trato gastrointestinal, denominada complexo mioelétrico migratório. Após a administraçäo de alimentos, o complexo mioelétrico migratório foi abolido e substituído por um outro de atividade mioelétrica prandial, cuja duraçäo e freqüência dos potenciais de açäo dependiam do tipo de alimento. A colecistoquinina e a pentagastrina aumentaram e o glucagon e a secretina diminuiram a freqüência dos potenciais de açäo no esfíncter de Oddi. Conclui-se que o esfíncter de Oddi pode desempenhar a funçäo importante de propelir e coordenar o tempo e o volume de drenagem para o duodeno

Glomerulopressin activity in peripheral blood of newly diagnosed type I (insulin-dependent) diabetic patients and in normal subjects treated with glucagon

Se estudió en dos ensayos biológicos la actividad de glomerulopresina en sangre periférica de voluntarios normales, pacientes diabéticos Tipo I (insulino-dependientes) de reciente diagnóstico (DID), y en voluntaríos normales tratados con glucagon. Los dos bioensayos fueron: a) variación en la tensión tónica contráctil del fundus de estómago de rata (TTC), y b) aumento de la presión ureteral del sapo que es considerada como índice de la presión glomerular (delta IPG). El ultrafiltrado obtenido de cuatro voluntarios normales tuvo una pequeña actividad en el TTC, y en otros dos sujetos no se observó actividad. El ultrafiltrado de cinco de estos sujetos no tuvo actividad en el delta IPG. El ultrafiltrado de los pacientes DID fue activo en los bioensayos. En tres de los ultrafiltrados de los normales tratados con glucagon el ultrafiltrado fue muy activo en el TTC, y en otros tres sujetos tratados con glucagon el ultrafiltrado fue poco activo en el TTC. En cinco de los voluntarios tratados con glucagon el ultrafiltrado fue muy activo en el ensayo del sapo. Estas observaciones sugieren que la actividad de glomerulopresina está aumentada en la sangre periférica de los pacientes DID de reciente diagnóstico y en sujetos normales tratados con glucagon

Inhibition of the glucagon induced incorporation of orthophosphate into the liver by gluconeogenic blockers

Hígados aislados de ratas alimentadas, fueron perfundidos con un medio preparado a partir de solución KRB a la cual se añadieron: seroalbúmina bovina, 3g/dl; glucosa, 90 mg/dl; ortofosfato para obtener una concentración en el plasma de 1 mg/dl; 18 por ciento de glóbulos rojos de rata lavados; pH, 7.40, fase gaseosa O2 95%-CO2 5%. Flujo 36 ml/min. Temperatura, 37-C. Volumen del perfusado 70 ml. 0,5 micronCi de 32P-ortofosfato por ml. fueron añadidos al perfusado diez minutos antes de montar el hígado: el tiempo, 15 minutos después de montar el órgano, se tomó como punto cero. En los experimentos en los cuales se emplearon los bloqueadores de la neoglucogénesis ( quinolinato 1,68 mM o aminoóxi-acetato 0.2 mM) éstos fueron añadidos al perfusado al tiempo 15 min. el glucagon, cuando fue administrado, se empleó en inyección continua entre 45 y 90 min. (20 microngm). Se tomaron muestras cada 15 minutos hasta 120 minutos, que se recogieron en tubos enfriados en hielo. Glucosa en el perfusado, Pi en el plasma, 32Pi en perfusado y actividad específica del Pi plasmático fueron los parámetros determinados. Se calcularon Deltas a partir de 45 min. Los valores de glucosa y de Pi plasmático se corrigieron a partir de blancos obtenidos, haciendo circular el perfusado en ausencia del hígado y los resultados se expresaron por 10g de hígado fresco