Doxepin therapy for postprandial symptomatic hypoglycaemic patients: neurochemical, hormonal and metabolic disturbances.

1. Three oral glucose tolerance tests were performed in each of 32 symptomatic postprandial hypoglycaemic patients (before placebo, before doxepin therapy and after doxepin therapy). Plasma neurotransmitters were determined in parallel with assays of plasma insulin and glucose levels. 2. Three different types of patients were distinguished. Type I showed a low noradrenaline/adrenaline ratio, high dopamine levels and low platelet 5-hydroxytryptamine (serotonin) levels during basal periods. After a glucose load, late peaks of dopamine and free 5-hydroxytryptamine, which coincided with the symptoms but not with the nadir of plasma glucose, were observed. Type II showed a low basal plasma noradrenaline/adrenaline ratio. After a glucose load, progressive increases in adrenaline and decreases in glucose were seen. Adrenergic symptoms coincided with the nadir of glucose. Although type III patients showed hyperinsulinaemia after a glucose load similar to the other types of patient, they did not show hyperglycaemia, but rather exhibited a sustained and progressive reduction in plasma glucose. These patients were characterized by a high basal plasma noradrenaline/adrenaline ratio, high basal plasma levels of 4-hydroxy-3-methoxyphenylethyleneglycol and high basal levels of platelet 5-hydroxytryptamine, all of which increased after a glucose load. Systolic and diastolic blood pressure decreases paralleled reductions in heart rate and glucose. The nadir of plasma glucose occurred simultaneously with the appearance of symptoms (weakness, heartburn, oppressive chest pain, tension headache, abdominal cramps, dizziness, etc.). Therapy with doxepin led to disappearance of the symptoms within 3-4 weeks. Normalization of all other disordered variables (cardiovascular, metabolic and neurochemical, and the clonidine test) paralleled the disappearance of the symptoms. 3. Symptoms varied in the three types of patients and we conclude that they are related to hypoglycaemia-induced disorders of plasma neurotransmitters, rather than to hypoglycaemia per se. We postulate that an uncoping stress situation (type I and II patients) and depression (type III patients) underlie the physiopathological mechanisms.

Pre-and post-prandial plasma levels of intermediate density lipoproteins in type 2 diabetic female patients

Hemos investigado los efectos del buen control de la diabetes sobre la composición química de las lipoproteínas plasmáticas de densidad intermedia (IDL) y las lipoproteínas de muy baja densidad (VLDL) en 8 mujeres diabéticas de Tipo 2, post-menopáusicas y 4 controles sanas. Se estudiaron muestras de plasma tomadas luego de 12-14h de ayuno y a las 3,6 y 8h después de la ingestión de una comida de prueba estandarizada. Antes del tratamiento el grupo diabético presentó concentraciones de colesterol, triglicéridos y proteínas en la fracción de IDL significativamente más altos que en el período post-tratamiento. También el modelo apolipoproteico en IDL cambió significativamente en el período pre-tratamiento y se pudo detectar apo B, apo E, apo C-I, apo C-II y apo C-III en 7 de las 8 pacientes, mientras que en el período de buen control de la diabetes, apo C-II y apo C-III estaban ausentes en 6 de las pacientes. En el grupo control apo C-II y apo C-III se encontraron sólo en 2 fraccciones de IDL aisladas de muestras tomadas a las 6h después de la comida. En las pacientes diabéticas las concentraciones plasmáticas de triglicéridos, colesterol y proteínas transportadas en VLDL no fueron afectadas por el tratamiento, pero los triglicéridos plasmáticos y los triglicéridos transportados en VLDL fueron más altos en los diabéticos que en el grupo control. El modelo apolipoproteico fue similar en ambos grupos diabéticos y en el grupo control. Nuestors resultados son consistentes con la hipótesis de que el buen control de la diabetes conduce a la disminución en el tiempo de residencia de IDL en el plasma, el cual se asocia a la disminución en su contenido de apo C. Consideramos que niveles plasmáticos elevados de IDL indican riesgo cardiovascular y que la normalización de este parámetro por el tratamiento, tanto en ayunas como en condiciones post-prandiales, debería considerarse como un criterio valioso para la estimación del buen control de la diabetes de Tipo 2 en mujeres (AU)

Pre-and post-prandial plasma levels of intermediate density lipoproteins in type 2 diabetic female patients

Hemos investigado los efectos del buen control de la diabetes sobre la composición química de las lipoproteínas plasmáticas de densidad intermedia (IDL) y las lipoproteínas de muy baja densidad (VLDL) en 8 mujeres diabéticas de Tipo 2, post-menopáusicas y 4 controles sanas. Se estudiaron muestras de plasma tomadas luego de 12-14h de ayuno y a las 3,6 y 8h después de la ingestión de una comida de prueba estandarizada. Antes del tratamiento el grupo diabético presentó concentraciones de colesterol, triglicéridos y proteínas en la fracción de IDL significativamente más altos que en el período post-tratamiento. También el modelo apolipoproteico en IDL cambió significativamente en el período pre-tratamiento y se pudo detectar apo B, apo E, apo C-I, apo C-II y apo C-III en 7 de las 8 pacientes, mientras que en el período de buen control de la diabetes, apo C-II y apo C-III estaban ausentes en 6 de las pacientes. En el grupo control apo C-II y apo C-III se encontraron sólo en 2 fraccciones de IDL aisladas de muestras tomadas a las 6h después de la comida. En las pacientes diabéticas las concentraciones plasmáticas de triglicéridos, colesterol y proteínas transportadas en VLDL no fueron afectadas por el tratamiento, pero los triglicéridos plasmáticos y los triglicéridos transportados en VLDL fueron más altos en los diabéticos que en el grupo control. El modelo apolipoproteico fue similar en ambos grupos diabéticos y en el grupo control. Nuestors resultados son consistentes con la hipótesis de que el buen control de la diabetes conduce a la disminución en el tiempo de residencia de IDL en el plasma, el cual se asocia a la disminución en su contenido de apo C. Consideramos que niveles plasmáticos elevados de IDL indican riesgo cardiovascular y que la normalización de este parámetro por el tratamiento, tanto en ayunas como en condiciones post-prandiales, debería considerarse como un criterio valioso para la estimación del buen control de la diabetes de Tipo 2 en mujeres

Effects of captivity on glucose tolerance in dogs.

Captivity decreased tolerance to glucose and increased blood serotonin levels in 6 normal dogs investigated. Return to freedom brought normalization in the glucose tolerance test and reverted blood serotonin to control levels.

The effects of dopaminergic blocking agents on the glucose tolerance test in 6 humans and 6 dogs.

Pre-treatment with low doses of sulpiride, an atypical dopaminergic blocking agent, but not haloperidol, a classical dopaminergic blocking agent, decreased tolerance to glucose and increased blood serotonin levels in 6 normal humans and 6 normal dogs investigated.

[Angiographic aspects of tumors of the islet of the pancreas]. / Aspectos angiográficos de los tumores de los islotes del páncreas.

Four patients with islet cell tumours were explored with selective angiography. The radiological findings of 3 insulinomas and 1 nonfunctioning tumor are described. The typical hypervascular pattern of parenchimatose phase was found in all. The three insulinomas were successfully treated surgically. The nonfunctioning tumor was not removed due to the pathologists original impression that it was a maligant tumor involving the portal vein. Angiographic pattern, etiology, differential diagnosis and causes of errors are discussed. The method is diagnostically useful and offers important precperative information thus reducing operating time and minimizing the magnitude of the surgery.

The effect of serotonin (5-HT) on insulin secretion.

The present study was aimed at observing the effect on insulin secretion of serotonin (5-HT) administered intraportally to anesthetized adult dogs. The influence of 5-HT on insulin release was also studied in mouse pancreatic islets isolated by a collagenase method. In the in vivo studies, 6 mg of 5-HT rapidly injected in the portal vein of dogs induced hypoglycemia, and a significant increase of immunoreactive insulin plasma levels (IRI) in blood samples taken from the pancreatoduodenal vein. The phenomenon was registered throughout three consecutive 10 min periods after serotonin administration. With 3 mg of 5-HT the IRI increases were not observed. When serotonin was slowly infused at doses of 3 and 6 mg, no increases of IRI were recorded. In the in vitro studies, 5-HT at 100 mug/ml stimulated the output of insulin in the presence of a low concentration of glucose (0.6 mg/ml); when the islets were incubated with glucose at a higher concentration (3.0 mg/ml) there was a lower insulin release in the presence of serotonin (100 mug/ml) than that obtained with glucose alone at the same concentration (3.0 mug/ml). The results obtained suggest that serotonin stimulates insulin release under certain conditions in the intact dog and also in the isolated pancreatic islets of the mouse incubated in vitro.

The effect of serotonin (5-HT) on insulin secretion.

The present study was aimed at observing the effect on insulin secretion of serotonin (5-HT) administered intraportally to anesthetized adult dogs. The influence of 5-HT on insulin release was also studied in mouse pancreatic islets isolated by a collagenase method. In the in vivo studies, 6 mg of 5-HT rapidly injected in the portal vein of dogs induced hypoglycemia, and a significant increase of immunoreactive insulin plasma levels (IRI) in blood samples taken from the pancreatoduodenal vein. The phenomenon was registered throughout three consecutive 10 min periods after serotonin administration. With 3 mg of 5-HT the IRI increases were not observed. When serotonin was slowly infused at doses of 3 and 6 mg, no increases of IRI were recorded. In the in vitro studies, 5-HT at 100 mug/ml stimulated the output of insulin in the presence of a low concentration of glucose (0.6 mg/ml); when the islets were incubated with glucose at a higher concentration (3.0 mg/ml) there was a lower insulin release in the presence of serotonin (100 mug/ml) than that obtained with glucose alone at the same concentration (3.0 mug/ml). The results obtained suggest that serotonin stimulates insulin release under certain conditions in the intact dog and also in the isolated pancreatic islets of the mouse incubated in vitro.

The effect of serotonin (5-HT) on insulin secretion

The present study was aimed at observing the effect on insulin secretion of serotonin (5-HT) administered intraportally to anesthetized adult dogs. The influence of 5-HT on insulin release was also studied in mouse pancreatic islets isolated by a collagenase method. In the in vivo studies, 6 mg of 5-HT rapidly injected in the portal vein of dogs induced hypoglycemia, and a significant increase of immunoreactive insulin plasma levels (IRI) in blood samples taken from the pancreatoduodenal vein. The phenomenon was registered throughout three consecutive 10 min periods after serotonin administration. With 3 mg of 5-HT the IRI increases were not observed. When serotonin was slowly infused at doses of 3 and 6 mg, no increases of IRI were recorded. In the in vitro studies, 5-HT at 100 mug/ml stimulated the output of insulin in the presence of a low concentration of glucose (0.6 mg/ml); when the islets were incubated with glucose at a higher concentration (3.0 mg/ml) there was a lower insulin release in the presence of serotonin (100 mug/ml) than that obtained with glucose alone at the same concentration (3.0 mug/ml). The results obtained suggest that serotonin stimulates insulin release under certain conditions in the intact dog and also in the isolated pancreatic islets of the mouse incubated in vitro.