A study of premature ovarian failure in Turkish women.

The parameters that could be responsible for or could be the end results of the premature ovarian failure were evaluated in 100 patients and compared with the same parameters of a control group consisting of 30 ovulatory healthy women with regular menstrual cycles. The incidence of premature ovarian failure was 6.6%.

Methodology for assaying iodide conductance in proteoliposomes: specific induction by thyroid membrane protein.

A sensitive assay is developed to assess the existence of an iodide channel in a fraction of solubilized membrane proteins. This step is critical when considering various procedures for purification of this channel. Sodium cholate is used as a detergent as it does not denature the iodide channel.

Dual effect of formycin A upon the hydrolysis of phosphoinositides in perifused pancreatic islets.

Formycin A (1.0 mM) caused a rapid, sustained and rapidly reversible inhibition of effluent radioactivity in rat pancreatic islets prelabelled with myo-[2-3H]inositol and perifused in the presence of 8.3 mM D-glucose.

Restricted effect of formycin A and non-glucidic nutrients upon insulin release in islets from rats with hereditary or acquired non-insulin-dependent diabetes.

Pancreatic islets isolated from control rats, Goto-Kakizaki rats and adult rats that were injected with streptozotocin during the neonatal period were incubated for two successive period of 90 min each in the presence of D-glucose (11.1 mM) with or without formycin A (1.0 mM), and in the presence of the dimethyl ester of succinic acid (SAD, 10.

Hydrolysis of succinic acid dimethyl ester in rat pancreatic islets.

The hydrolysis of the dimethyl ester of [1,4-14C]succinic acid and/or [2,3-14C]succinic acid was measured in homogenates of rat pancreatic islets, liver, jejunum, brain, BC3H1 mouse myocytes, NG108-19 mouse neuroblastoma x rat glioma hybrid cells, and Caco-2 human colon adenocarcinoma cells. The specific activity of the enzyme was much higher in liver, jejunum, and Caco-2 cells than in the other cell types. The affinity of the enzyme for succinic acid dimethyl ester (SAD) was also much higher in liver than in islet homogenates.

Impaired activity of rat pancreatic islet mitochondrial glycerophosphate dehydrogenase in protein malnutrition.

In rats that received a low protein isocaloric diet (protein content of the diet: 8 instead of 20%) during fetal life and thereafter up to the time of sacrifice at 12-13 weeks of age, a low plasma insulin concentration, a decreased insulin content of isolated pancreatic islets, and an impaired secretory response of the islets to either D-glucose or the association of L-leucine and L-glutamine coincided, in islet homogenates, with a low activity of the mitochondrial glycerophosphate dehydrogenase and an abnormally high ratio between glutamate-alanine and glutamate-aspartate transaminase activities. Opposite enzymatic changes were found in liver extracts of the same rats. No obvious change in these hormonal, secretory, and enzymatic variables were observed when the period of protein deficiency was restricted to fetal life.

Hexose metabolism in pancreatic islets: regulation of the mitochondrial NADH/NAD+ ratio.

In rat pancreatic islets, D-glucose in concentrations exceeding 5.6 mM caused a concentration-related decrease of the mitochondrial NADH/NAD+ ratio, as judged from the changes in the islet content of glutamate, NH4+, and 2-ketoglutarate, and assuming that the glutamate dehydrogenase reaction is near equilibrium with the mitochondrial NAD system. The concentration dependency of the response to D-glucose was vastly different in islet and parotid cells, respectively.

Factitious hypoglycaemia documented by a modified assay for the measurement of plasma sulphonylurea.

Two cases of factitious hypoglycaemia due to intentional or inadvertent intake of glipizide by non-diabetic subjects were identified through the measurement of this sulphonylurea in plasma by a modified assay procedure.

Standardized procedure for the assay and identification of hypoglycemic sulfonylureas in human plasma.

A standardized procedure for the assay and identification of hypoglycemic sulfonylureas in plasma is presented. External standards and plasma extracts containing glibenclamide, gliquidone, glipizide, or gliclazide were examined by high-performance liquid chromatography. The four sulfonylureas could be identified and measured with a precision of 5%-7% and a limit of detection close to 1-2 ng in injected external standards and 10-40 ng/ml in plasma samples.

Hexose metabolism in pancreatic islets: effect of D-glucose on the mitochondrial redox state.

The mitochondrial NADH/NAD+ ratio for free nucleotides in rat pancreatic islets was judged from the cell content in L-glutamate and L-alanine, 2-ketoglutarate and pyruvate, and NH4+. At a physiological concentration of D-glucose, such a ratio averaged 9.6 +/- 1.

The iodide channel of the thyroid. II. Selective iodide conductance inserted into liposomes.

An iodide channel has been previously identified in the plasma membrane of bovine throcytes [Golstein et al., Am. J.

Enzymatic and secretory activities in pancreatic islets of non-insulin-dependent diabetic rats after short-term infusion of succinic acid monomethyl ester.

The monomethyl ester of succinic acid (SME) was recently proposed as a novel tool for stimulation of proinsulin biosynthesis and insulin release in animal models of non-insulin-dependent diabetes mellitus. In the present study, either saline or SME (14 mmol/day) was infused for 3 days to control rats, animals injected with streptozotocin during the neonatal period, and Goto-Kakizaki rats with inherited diabetes. The infusion of SME failed to correct the anomalies found in the islets of diabetic rats, namely, a decreased activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, a low insulin content, and an impaired secretory response to various nutrient secretagogues including D-glucose, 2-ketoisocaproate, and the combination of L-leucine and L-glutamine.

Metabolic effects and fate of succinic acid methyl esters in rat hepatocytes.

The metabolic fate and metabolic effects of succinic acid methyl esters were examined in rat isolated hepatocytes. Both the monomethyl ester (SAM) and dimethyl ester (SAD) of succinic acid inhibited D-glucose metabolism. Such an inhibition affected, in order of increasing severity, the direct incorporation of D-glucose into glycogen and futile cycling between the hexose and its 6-phosphate ester, the phosphorylation of D-glucose, the generation of triose phosphates from the hexose, and the production of 14C-labeled lactate, pyruvate, and amino acids from D-[U-14C]glucose and its oxidation.

Insulinotropic action of glutamic acid dimethyl ester.

Glutamic acid dimethyl ester (GME; 3.0-10.0 mM) enhanced insulin release evoked by 6.

13C NMR study of C2- and C3-deuterated lactic acid production by parotid cells exposed to 13C-labeled glucose in the presence of D2O.

The generation of C2- and C3-deuterated lactic acid produced by rat parotid cells exposed to [1-13C] glucose, [2-13C]glucose, and [6-13C]glucose in the presence of D2O was assessed by 13C NMR. The results indicated that the escape from deuteration amounted to about 46% at the phosphoglucoisomerase level, 100% at the phosphomannoisomerase level, 65% in the reactions catalyzed by phosphofructoaldolase and triose phosphate isomerase, and 58% at the level of glutamate pyruvate transaminase. Such high values are considered to support a possible enzyme-to-enzyme tunneling of metabolic intermediates at selected sites in the glycolytic pathway.

Protective action of succinic acid monomethyl ester against the impairment of glucose-stimulated insulin release caused by glucopenia or starvation: metabolic determinants.

The monomethyl ester of succinic acid (SME) was recently found to protect pancreatic islet B-cells against the impairment of glucose-stimulated insulin release caused by either glucopenia or starvation. The possible metabolic determinants of such a protective action are now scrutinized. After 180 min preincubation at 2.

Insulinotropic action of formycin A.

The adenosine analogue formycin A is phosphorylated to its triphosphate ester in a sequence of reactions catalyzed by adenosine kinase and adenylate kinase. Formycin A triphosphate is an ATP analogue that is currently used to probe for ATP binding sites. Considering the key role ascribed to ATP in the coupling of metabolic to cationic events in the process of glucose-stimulated insulin release, we investigated whether formycin A displays insulinotropic action in rat pancreatic islets.

Pancreatic islet response to dicarboxylic acid esters in rats with type 2 diabetes: enzymatic, metabolic and secretory aspects.

This study aimed to compare the metabolic and secretory responses of pancreatic islets from animals with non-insulin-dependent diabetes to D-glucose with the effects of the methyl esters of succinic acid (SME) and glutamic acid (GME). The insulin secretory response to D-glucose was impaired in islets from rats with diabetes which was either inherited (Goto-Kakizaki (GK) rats) or acquired (streptozotocin-treated (STZ) rats). This coincided with a preferential alteration of oxidative relative to total glycolysis in intact islets and a selective defect of FAD-linked mitochondrial glycerophosphate dehydrogenase (m-GDH) in islet homogenates.

Hexose metabolism in pancreatic islets UDP-glucose pyrophosphorylase activity.

UDP-glucose pyrophosphorylase was measured in rat pancreatic islets, the generation of D-glucose 1-phosphate from UDP-glucose and PPI being eventually coupled to the generation of L-[U-14C]glutamate from 14C-labelled alpha-ketoglutarate. The activity of the enzyme was about one order of magnitude lower in islet than liver homogenates. The affinity of the enzyme for either UDP-glucose or PPi was comparable, however, in liver and islets.

Impaired FAD-glycerophosphate dehydrogenase activity in islet and liver homogenates of fa/fa rats.

The mitochondrial FAD-linked enzyme glycerophosphate dehydrogenase plays a key role in the pancreatic B-cell glucose sensing device. In the present study, the activity of this enzyme was examined in islets of fa/fa rats in which inherited diabetes mellitus is associated with obesity, hyperinsulinism and severe insulin resistance. The specific activity of both FAD-linked glycerophosphate dehydrogenase and glutamate dehydrogenase were decreased in islet and liver homogenates prepared from fa/fa, as compared to Fa/Fa, rats, this coinciding with a low ratio between glutamateoxalacetate and glutamate-pyruvate transaminase activity in both islet and liver extracts, islet hyperplasia, hyperinsulinemia and hepatic steatosis in the hyperglycemic fa/fa rats.

Secretory, biosynthetic, respiratory, cationic, and metabolic responses of pancreatic islets to palmitate and oleate.

Palmitate and oleate (0.5 to 1.0 mM) caused a time- and concentration-related augmentation of insulin release evoked by D-glucose (6.

Enzymatic, metabolic and secretory patterns in human islets of type 2 (non-insulin-dependent) diabetic patients.

Islets were isolated by automatic digestion from non-diabetic cadaveric organ donors and from Type 2 (non-insulin-dependent) diabetic subjects. The activity of FAD-glycerophosphate dehydrogenase, but not that of either glutamate dehydrogenase, glutamate-oxalacetate transaminase or glutamate-pyruvate transaminase, was lower in Type 2 diabetic patients than control subjects. Hexokinase, glucokinase and glutamate decarboxylase activities were also measured in islets from control subjects.

Insulinotropic action of the D-glucosyl and 3-O-methyl-D-glucosyl monomethyl esters of succinic acid.

Succinic acid methyl esters are currently under investigation as potential insulinotropic tools in animal models of non-insulin-dependent diabetes mellitus. The in vivo administration of these esters may result in the undesirable generation of methanol through their intracellular hydrolysis. As a first attempt to circumvert this drawback, we have now investigated whether the esterification of the carboxylic group of succinic acid monomethyl ester by D-glucose or 3-O-methyl-D-glucose affects its insulin-otropic action.

Insulinotropic action of AICA riboside. II. Secretory, metabolic and cationic aspects.

Preincubation of rat pancreatic islets with AICA riboside (0.1 to 1.0mM) caused a concentration-related stimulation of both 45Ca net uptake and insulin release evoked by 8.

Metabolism of endogenous nutrients in islets of Goto-Kakizaki (GK) rats.

The metabolism of endogenous nutrients was examined in pancreatic islets of control and Goto-Kakizaki (GK) rats. At the ultrastructural level, no glycogen was found in the islet cells of GK rats, a situation similar to that prevailing in normal islets. Likewise, by measuring the output of L-lactate from islets first incubated at 16.