Síndrome do glucagonoma: relato de caso / Glucagonoma syndrome: a case report

Relato de caso de síndrome do glucagonoma, cartacterizada por lesöes de pele tipo eritema necrolítico migratório, emagrecimento e piora de diabetes tipo II (preexistente) em um homem de 69 anos. Na suspeita diagnóstica, foi realizada investigaçäo laboratorial e de imagem. Evidenciou-se processo expansivo no pâncreas e foi realizada cirurgia abdominal, sendo detectadas metástases disseminadas. Optou-se por tratamento sintomático, e o paciente evoluiu para óbito em outro serviço. Näo foi realizada necrópsia. Os glucagonoma säo tumores na maioria solitários, sendo o tratamento cirúrgico precoce curativo; entretanto, a maioria é invasiva na ocasiäo do diagnóstico, tornando o prognóstico ruim. Ressaltam-se a raridade da síndrome e a importância do diagnóstico precoce

Ca2+ dependence of gluconeogenesis stimulation by glucagon at different cytosolic NAD+-NADH redox potentials

The influence of Ca2+ on hepatic gluconeogenesis was measured in the isolated perfused rat liver at different cytosolic NAD+-NADH potentials. Lactate and pyruvate were the gluconeogenic substrates and the cytosolic NAD+-NADH potentials were changed by varying the lactate to pyruvate rations from 0.01 to 100. The following results were obtained: a) gluconeogenesis from lactate plus pyruvate was not affected by Ca2+-free perfusion (no Ca2+ in the perfusion fluid combined with previous depletion of the intracellular pools); gluconeogenesis was also poorly dependent on the lactate to pyruvate rations in the range of 0.1 to 100; only for a ratio equal to 0.01 was a significantly smaller gluconeogenic activity observed in comparison to the other rations. b) In the presence of Ca2+, the increase in oxygen uptake caused by the infusion of lactate plus pyruvate at a ratio equal to 10 was the most pronounced one; in Ca2+-free perfusion the increase in oxygen uptake caused by lactate plus pyruvate infusion tended to be higher for all lactate to pyruvate ratios; the most pronounced difference was observed for a lactate/pyruvate ratio equal to 1.c) In the presence of Ca2+ the effects of glucagon on gluconeogenesis showed a positive correlation with the lactate to pyruvate rations; for a ratio equal to 0.01 no stimulation ocurred, but in the 0.1 to 100 range stimulation increased progressively, producing a clear parabolic dependence between the effects of glucagon and the lactate to pyruvate ratio. d) In the absence of Ca2+ the relationship between the changes caused by glucagon in gluconeogenesis and the lactate to pyruvate ratio was substantially changed; the dependence curve was no longer parabolic but sigmoidal in shape with a plateau beginning at a lactate/pyruvate ratio equal to 1; there was inhibition at the lactate to pyruvate ratios of 0.01 and 0.1 and a constant stimulation starting with a ratio equal to 1; for the lactate to pyruvate ratios of 10 and 100, stimulation caused by glucagon was much smaller than that found when Ca2+ was present. e) The effects of glucagon on oxygen uptake in the presence of Ca2+ showed a parabolic relationship with the lactate to pyruvate ratios which was closely similar to that found in the case of gluconeogenesis.

glucagon et les glucagonomes

Ghucagon is a pancreatic peptide, secreted by the A cells of the pancreatic islets of Langerhans under the influence of a certain number of regulating factors. This 29 amino-acids peptide has essentially a hyperglycemic action because it mobilizes all the organism's energetic reserves, and will therefore oppose insulin hypoglycemias. Its other actions are less known and are only expressed at supraphysiological levels such as its muscle relaxant effect on the digestive smooth muscle fibers, or its cardiac stimulant effect. Some authors have attributed recently to glucagons a role in the regulation of thirst and satiety, and that may lead to some interesting therapeutic actions such as in obesity. Its regulating action on liver cells has not been proven yet at least in severe hepatic lesions. Glucagonomas are rare neuroendocrine tumors, usually malignant, that develop in the endocrine pancreas and have a clinical picture characterized by the presence of the 4 D syndrome [migratory necrolytic dermatitis, diabetes mellitus, deep-vein thrombosis, and depression]. The tumor causing the hyperglucagonemia has a slow growth that explains its often important volume and the existence of metastasis in 60% of the cases at the time of diagnosis. Apart from the metastatic invasion, and as is the case in other neuroendocrine tumors, there are no definite criteria of histological malignancy. The definitive treatment of glucagonoma is surgical removal of the tumor, flanked or not by a treatment with somatostatin analogues that are active because of the existence of somatostatin receptors in neuroendocrine tumors. Radioactive somatostatin is utilized for the detection of metastatic sites but also as a therapeutic tool. Concerning whole-body scanning, the use of radiolabeled somatostatin has proven to be one of the high-performance techniques, but also a very sensitive one. As far as treatment is concerned, somatostatin radioactive analogues are increasingly replacing conventional radiotherapy as well as conventional chemotherapy