Studies on the mechanism of xylitol-induced insulin secretion in dogs

Summary The effect of infusion of small doses of xylitol into the pancreatic artery upon insulin release was studied in anaesthetized dogs, in order to decide whether the strong insulin-releasing effect of xylitol in dogs is mediated by a direct action of xylitol upon the islets or indirectly by some of its metabolites. Xylitol or glucose was infused at 0.5–1.0 mg/kg · min either into the femoral vein or into the superior pancreaticoduodenal artery, and the changes in plasma insulin were measured in the superior pancreaticoduodenal vein. Infusion into the pancreatic artery always resulted in a sharp increase in insulin release, whereas intravenous infusion caused no or little increase. Infusion of xylitol into the superior pancreaticoduodenal artery produced a prompt increase in plasma insulin in the superior pancreaticoduodenal vein but not in the splenic vein. These data suggest that xylitol has a direct stimulatory effect upon islet cells. — During intravenous infusion of epinephrine (1.0 g/kg. min), plasma insulin did not increase despite intravenous administration of glucose or xylitol (0.4 g/kg). There was a rebound rise of plasma insulin after cessation of epinephrine infusion. Plasma insulin responses to intravenous injection of glucose or xylitol (0.4 g/kg) were inhibited also by the intravenous infusion of diazoxide (0.2 mg/kg · min), but this was somewhat variable among individual dogs. The suppression by epinephrine or diazoxide of both glucose and xylitol-induced hyperinsulinaemia may suggest that there is some common mechanism between the insulin-releasing effects of glucose and xylitol.

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Untersuchungen zum Mechanismus der verstärkten Insulinsekretion unter Xylit

Zusammenfassung An anaesthesierten Hunden wurde die Wirkung der Infusion kleiner Xylit-Mengen in die Pankreasarterie auf die Insulinfreisetzung untersucht, um zu klären, ob das Xylit direkt oder über einen seiner Metabolite auf die Insulinausschüttung wirkt. Xylit oder Glucose wurde in Mengen von 0.5–1.0 mg/kg/min entweder in die Femoralvene oder in die A.pankreaticoduodenalis sup. infundiert und die Änderung des PlasmaInsulins in der V.pankreatico-duodenalis sup. gemessen. Zufuhr über die Pankreasarterie löste immer eine abrupte Steigerung der Insulinfreisetzung aus, während intravenöse Gaben zu keinem oder nur einem geringen Anstieg führten. Die Xylit-Infusion in die A.pankreaticoduodenalis sup.bewirkte zwar eine prompte Steigerung der Plasma-Insulinspiegel in der V.pankreatico duodenalis sup., nicht aber in der Milzvene. — Diese Befunde sprechen dafür, daß Xylit die Inselzellen direkt stimuliert. Während einer i.v.Infusion von 1.0 g/kg/min Adrenalin stieg das Plasma-Insulin trotz intravenöser Zufuhr von 0.4 g/kg Glucose oder Xylit nicht an. Nach Beendigung der Adrenalin-Infusion wurde ein verstärkter Wiederanstieg des Plasma-Insulins beobachtet. Auch durch i.v.Gaben von 0.2 mg/kg/min Diazoxid ließ sich die Wirkung der Infusion von 0.4 g/kg Glucose oder Xylit unterdrükken, wobei sich jedoch Unterschiede zwischen den einzelnen Tieren ergaben. Die Aufhebung des Xylit- u. Glucose-Effektes auf die Insulinsekretion durch Adrenalin und Diazoxid könnte darauf hinweisen, daß die Steigerung der Insulinfreisetzung durch Glucose und Xylit auf einem gemeinsamen Mechanismus beruht.

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Etudes sur le mécanisme de la sécrétion d'insuline provoquée par le xylitol chez des chiens

Résumé L'effet sur la sécrétion d'insuline de l'infusion de petites doses de xylitol dans l'artère pancréatique a été étudié chez des chiens anesthésiés, afin de savoir si l'effet fortement insulino-sécréteur du xylitol chez les chiens est dû à une action directe du xylitol sur les îlots ou à une action indirecte par l'intermédiaire de certains de ses métabolites. Le xylitol ou le glucose était infusé la dose de 0.5–1.0 mg/kg. min, soit dans la veine fémorale, soit dans l'artère pancréatico-duodénale supérieure, et les variations de l'insuline plasmatique étaient mesurées dans la veine pancréatico-duodénale supérieure. L'infusion dans l'artère pancréatique provoquait toujours une rapide augmentation de la sécrétion d'insuline, tandis que l'infusion intraveineuse ne causait pas ou peu d'augmentation. L'infusion de xylitol dans l'artère pancréaticoduodénale supérieure provoquait une augmentation prompte de l'insuline plasmatique dans la veine pancréatico-duodénale supérieure, mais pas dans la veine splénique. Ces données suggèrent que le xylitol a un effet stimulateur direct sur les cellules des îlots. — Pendant l'infusion intraveineuse d'adrénaline (1.0 g/kg. min), l'insuline plasmatique n'augmentait pas malgré l'administration intraveineuse de glucose ou de xylitol (0.4 g/kg). Après l'arrêt de l'infusion d'adrénaline, l'insuline plasmatique présentait un phénomène de rebound. Les réponses de l'insuline plasmatique l'injection intraveineuse de glucose ou de xylitol (0.4 g/kg) étaient également inhibées par l'infusion intraveineuse de diazoxide (0.2 mg/ kg. min), mais ceci était un peu variable selon les chiens. La suppression par l'adrénaline ou le diazoxide de l'hyperinsulinémie provoquée par le glucose et le xylitol peut suggérer qu'il existe un mécanisme commun entre les effets insulino-sécréteurs du glucose et du xylitol.

     

Cutoff value of 1 h, 50 g glucose challenge test for screening of gestational diabetes mellitus in a Japanese population

A total of 2651 consecutive native Japanese women who underwent a glucose challenge test (GCT) were retrospectively investigated. GCT was performed between 24 and 27 weeks of gestation; each subject received a 50 g oral glucose load without regard to the fasting or fed state, followed by a determination of 1 h venous plasma glucose level. Women demonstrating GCT exceeding 130 mg/dl received a 75 g, 2 h oral glucose tolerance test to determine whether or not they had gestational diabetes mellitus (GDM). All women with GDM were treated with a strict diabetic protocol including insulin therapy. Forty-nine (1.8%) women were diagnosed to have GDM. The receiver-operator characteristic curve identified a GCT finding above 140 mg/dl as the cutoff value for detecting GDM, which showed a sensitivity and specificity of 96 and 76%, respectively. Our results suggest that the cutoff value of a 50 g GCT is 140 mg/dl to identify pregnancies with GDM in a Japanese population.     

Carboxylic monolayer formation for observation of intracellular structures in HeLa cells with direct electron beam excitation-assisted fluorescence microscopy

Intracellular structures of HeLa cells are observed using a direct electron beam excitation-assisted fluorescence (D-EXA) microscope. In this microscope, a silicon nitride membrane is used as a culture plate, which typically has a low biocompatibility between the sample and the silicon nitride surface to prevent the HeLa cells from adhering strongly to the surface. In this work, the surface of silicon nitride is modified to allow strong cell attachment, which enables high-resolution observation of intracellular structures and an increased signal-to-noise ratio. In addition, the penetration depth of the electron beam is evaluated using Monte Carlo simulations. We can conclude from the results of the observations and simulations that the surface modification technique is promising for the observation of intracellular structures using the D-EXA microscope.OCIS codes: (170.0170) Medical optics and biotechnology, (170.0180) Microscopy     

Combined pure red cell aplasia and autoimmune hemolytic anemia in systemic lupus erythematosus with anti-erythropoietin autoantibodies

A 42-year-old woman with systemic lupus erythematosus was admitted to our hospital because of severe anemia. Her bone marrow was almost normocellular and erythroblasts were nearly absent. Laboratory data showed elevated levels of lactate dehydrogenase and positive findings on Coombs' tests. On the basis of these findings, her anemia was diagnosed as the overlap of pure red cell aplasia with autoimmune hemolytic anemia. Radioimmunoprecipitation assay revealed that her serum was positive for anti-erythropoietin antibodies before therapy. Furthermore, the autoantibodies inhibited proliferation of an erythropoietin-dependent cell line in a dose-dependent manner. Immunosuppressive treatment improved the anemia accompanied with disappearance of the autoantibodies.     

Transient elastography-derived liver stiffness measurements were found to be useful for predicting liver infiltration in a case of mature T-cell neoplasm involving liver dysfunction

Transient elastography (TE) is a novel, non-invasive imaging technique for measuring liver stiffness (LS). It is considered to be useful for predicting the severity of fibrosis and the risk of cirrhosis or hepatocellular carcinoma. However, the association between the presence of diffuse regions of increased cell density in the liver and elevated LS values has not been assessed. We experienced a case in which a mature T-cell neoplasm had invaded the liver, but the infiltrating lesion was not detected by contrast-enhanced computed tomography (CT) or fluorodeoxyglucose positron emission tomography/CT scans. Instead, the tumor’s presence was indicated by the change in the patient’s TE-derived LS values after chemotherapy. At diagnosis liver dysfunction was detected in a biochemical examination, and mean LS value was as high as 25.4 kPa [interquartile range (IQR): 0.3, success rate (SR):100%]. After chemotherapy, the patient’s mean LS value fell to 4.3 kPa (IQR: 0.8, SR:100%). A follow-up pathological investigation demonstrated that proliferating abnormal T-cells were no longer present in the patient’s liver. This is the first report to describe the use of LS data to support a diagnosis of liver infiltration by tumor cells exhibiting a portal and sinusoidal distribution pattern rather than a focal pattern. Elevated TE-derived LS values should lead to hepatic tumor infiltration being considered during initial examinations or a suspicion of recurrence during follow-up examination of lymphoma patients who achieve complete remission, even when radiological investigations do not detect abnormalities in the liver.