Sant P. Singh

Effect of ethanol and its metabolites on glucose mediated insulin release from isolated islets of rats.

Effects of ethanol and its metabolites, acetaldehyde and acetate, on insulin secretion were studied in isolated islets from normal rats. Addition of ethanol to the incubation media inhibited glucose mediated insulin release in a dose related manner. Prior exposure of islets to ethanol during the preincubation period had no influence on subsequent insulin response to either glucose or glucose plus ethanol. Acetaldehyde inhibited while sodium acetate potentiated insulin response to glucose. It is concluded that ethanol has a direct inhibitory effect on glucose mediated insulin release from rat islets.

National General Practice Study of Epilepsy and Epileptic Seizures: Objectives and Study Methodology of the Largest Reported Prospective Cohort Study of Epilepsy

Most available data on the prognosis of epileptic seizures come from hospital-based clinics in which patients with chronic or severe disease are over-represented. The National General Practice Study of Epilepsy and Epileptic Seizures is a large prospective community-based study of people with newly diagnosed seizures which aims to address questions related to the early prognosis of epilepsy. 275 general practitioners throughout the United Kingdom have registered a total of 1,195 patients. In this paper we discuss the background to the study and the methodology used.

Effects of ethanol on carbohydrate metabolism: I. Influence on oral glucose tolerance test.

To study the effect of ethanol on glucose tolerance test, a series of experiments were performed on Sprague-Dawley male rats weighing 250 g. After 18-hr fast, each rat was given, at random, the following test substances (one test substance at a time) intragastrically in a volume of 0.5 ml/100 g body weight: saline; glucose 0.75 g/kg (3 kcal); ethanol 0.4 g/kg (3 kcal); and ethanol with glucose. Saline or ethanol alone produced no significant changes in blood glucose or plasma insulin concentrations. Addition of ethanol to glucose load resulted in glucose intolerance as well as a lower and sluggish insulin response when compared to these with glucose load alone. The results suggest that ethanol per se has no effect on blood glucose or plasma insulin. However, when given together with glucose load, ethanol produces glucose intolerance as well as inhibition of glucose mediated insulin response.

Maternal alcohol ingestion inhibits fetal glucose uptake and growth

The distribution of maternally-derived glucose was determined in selected tissues of fetuses from ethanol-fed (EF) rats and from pair-fed (PF) and ad lib-fed (AF) controls. Maternal ethanol ingestion resulted in reduced fetal brain and liver weights and lower liver and lung glycogen levels compared to those of the PF or AF control groups. In addition, experimental fetuses exhibited reduced uptake of maternally-derived [3H] 2-deoxy-D-glucose (2-DG) by placenta and fetal brain. Fetal body, liver, lung, and brain weights correlated with fetal plasma 3H activity and with the fetal:maternal plasma 3H ratio, an indicator of the rate of placental glucose transfer. Brain weight correlated with 2-DG content per gram tissue weight. These observations suggest that reduced nutrient availability due to impaired placental transfer plays a role in the intrauterine growth retardation associated with maternal ethanol ingestion.

Routine Blood Chemistry Screen: A Diagnostic Aid for Alzheimer's Disease

Results of blood chemistry screens of 47 Alzheimers disease patients were compared to those of 71 non-Alzheimers disease patients with other dementias. Only kidney-related tests differed between the groups (urea nitrogen, creatinine, uric acid and albumin) with the Alzheimers disease patients nearer the normal ranges. Multivariate analyses were used to examine whether the simultaneous use of the analytes could aid in diagnosing Alzheimers disease. Linear and quadratic discriminant analysis and logistic regression were used to evaluate a number of models. A linear discriminant model of albumin, uric acid, lactate dehydrogenase, and age demonstrated 70-75% classification accuracy using randomly selected test populations of 20%.

Ethanol influence on insulin secretion from isolated rat islets

This study was done to delineate the role of α- and β-adrenergic receptors and cyclic AMP in the mechanism of ethanol effects on insulin release from isolated islets. Rats were given an α-adrenergic blocker, phentolamine, or a β-adrenergic blocker, propranolol. In addition, ethanol 1 g/kg was given intragastrically 1 h prior to sacrifice. Glucose mediated insulin release from isolated islets was enhanced by phentolamine and decreased by propranolol. Ethanol treatment inhibited glucose-induced insulin release from isolated islets of control rats as well as those given phentolamine and/or propranolol. Insulin release from isolated islets in response to dibutyryl-cyclic AMP was attenuated by ethanol. Theophylline enhanced glucose mediated insulin release from control islets but ethanol treatment produced a significant inhibition of insulin response. The data suggest that the site of action of the deleterious effects of ethanol on insulin release from isolated islets in rat does not involve adrenergic system and cyclic AMP.

Effects of ethanol on glucose turnover in pregnant rats

Glucose turnover was measured in term pregnant rats fed ethanol (30% of caloric intake) throughout gestation. Ethanol ingestion significantly reduced maternal weight gain and term fetal body weight when compared to pair-fed or ad libitum-fed controls. At term the blood glucose level and 6-3H-glucose turnover were reduced when compared to either control group. The rate of gluconeogenic recycling, indicated by the difference between 6-3H and 6-14C-glucose turnover determinations, was reduced by ethanol ingestion to half that of the control groups. Glucose turnover correlated with both conceptus weight and blood glucose level. Impaired maternal glucose homeostasis, including a reduced gluconeogenic response to the metabolic demands of late pregnancy, may thus contribute to the effects of ethanol on intrauterine growth.

Ethanol influence on calcium uptake and insulin release by rat islets

Effect of acute ethanol treatment on simultaneous 45Ca++ uptake and insulin response to glucose was measured in isolated rat pancreatic islets. Ethanol, given ip 1 gm/Kg 1 h prior to sacrifice of the animal, decreased significantly 45Ca++ uptake and insulin response to 8.3 and 16.7 mM glucose. Addition of ethanol to the incubation media inhibited 45Ca++ uptake and insulin release in a dose-related matter. Inophore A23187, which is known to enhance 45Ca++ efflux, decreased 45Ca++ uptake without affecting insulin release. Inhibitory effects of ethanol and ionophore A23187 were not additive when islets were exposed to both test substances simultaneously. Forskolin, an activator of the adenylate cyclase system potentiated the glucose mediated insulin response in rat islets. However, ethanol decreased the insulin response of islets exposed to glucose and forskolin. The data show that ethanol inhibits 45Ca++ uptake response to glucose and that ethanol influence on insulin release may involve a site beyond the formation of cyclic AMP in the process of excitation-secretion coupling.

Effect of thyrotoxicosis on ethanol metabolism and on hepatic ethanol oxidation enzymes

The influence and mechanism of action of T4 treatment on ethanol metabolism was investigated by the determination of ethanol elimination in intact rats and by the estimation of alcohol dehydrogenase and the microsomal ethanol oxidizing system activity in isolated rat liver. The rate of ethanol degradation was significantly decreased to 65% of control values in T4-treated rat liver. Similarly blood ethanol disappearance rate was significantly inhibited in thyrotoxic rats as compared to euthyroid animals. Hepatic alcohol dehydrogenase activity was reduced to 39% of control values as a result of T4 treatement; however, the microsomal ethanol oxidizing system activity was not affected. These data suggest that reduction in blood ethanol disappearance rate is associated with inhibition of hepatic alcohol dehydrogenase activity in thyrotoxicosis.