Search PubMed⌕ Search

Biomedical subjects

E Cerasi

Publications and source records attributed to E Cerasi.

At least 127 records · Page 7Linked to original sources
PubMed1977

[The role of cyclic AMP in the control of insulin secretion (author's transl)].

D-glucose stimulates the accumulation of cyclic AMP in isolated islets of Langerhans in a dose-dependent manner. This effect is present as long as the sugar remains elevated in the incubate. Under present experimental conditions the stimulation of cyclic AMP precedes insulin release. Islet or medium cyclic AMP, and insulin secretion are closely correlated at various incubation times. We conclude that the beta-cell cyclic AMP system is one of the major mediators of the glucose signal to insulin secretion. Tolbutamide and glibenclamide have similar effects in the absence or with low concentrations of glucose. These results may indicate that these sulfonylurea derivates act at sites where glucose exerts its effect.

Animals↗
PubMed1976

Pathways of carbohydrate oxidation during thermogenesis by the spadix of Arum maculatum.

1. The aims of this work were to discover the pathways of carbohydrate oxidation prior to and during thermogenesis by the club of the spadix of Arum maculatum, and whether there was coarse control of these pathways. 2. 14C02 production from [1-14C]-, [3,4-14C]-, and [6-14C]glucose, the detailed distribution of 14C from [1-14C]- and [6-14C]glucose, and the maximum catalytic activities of phosphofructokinase, fructose-1,6-diphosphate aldolase, glucose-6-phosphate dehydrogenase, and phosphogluconate dehydrogenase were determined at different stages in the development of the spadix. The results indicate that in the early stages carbohydrate is oxidized via both the pentose phosphate pathway and glycolysis, and that a shift to glycolysis occurs during development so that just before and during thermogenesis glycolysis predominates almost exclusively. 3. During development the activities of phosphofructokinase and glucose-6-phosphate dehydrogenase per club increased 100- ans during spadix development, and indicated that the onset of rapid glycolysis at thermogenesis is regulated by fine control or availability of substrate.

Fructose-Bisphosphate Aldolase↗
PubMed1976

Effect of hexoses and mannoheptulose on cyclic AMP accumulation and insulin secretion in rat pancreatic islets.

The effects of various sugars on the simultaneous release of insulin and accumulation of cyclic AMP were studied in collagenase isolated rat pancreatic islets. D-Glucose stimulated the formation of cyclic AMP at 3 and 60 min of incubation, whether measured by a label incorporation technique, or by the protein kinase binding assay of Gilman. Only D-glucose and D-mannose were able to stimulate insulin release and cyclic [3H]AMP accumulation in the absence of other substrate. D-fructose had a stimulatory effect in the presence of 3.3 mM D-glucose only at a high concentration (33.8 mM), and enhanced the effects of 8.3 mM glucose when added at the concentration of 8.3 mM. D-Galactose was effective only together with 8.3 mM D-glucose. The order of potency of these hexoses, both regarding insulin secretion and cyclic [3H]AMP accumulation, was glucose-mannose-fructose-galactose. L-Glucose and 3-O-methylglucose had no effects at 60 min when incubated together with 8.3 mM D-glucose, whereas at 3 min, 3-O-methylglucose induced a small stimulation of the cyclic [3H]AMP response. D-mannoheptulose and D-glucosamine inhibited the insulin and cyclic [3H]AMP responses to 27.7 mM glucose. Mannoheptulose suppressed completely the glucose effect on cyclic nucleotide accumulation within 90 s. Although under all incubation conditions, the threshold stimulatory or inhibitory concentration of a given agent was identical for insulin release and cyclic [3H]AMP accumulation, these two variables showed quantitative differences in incubations of 60 min, the magnitude of the changes in insulin secretion being larger than that for the cyclic nucleotide. It is suggested that modulation of islet cyclic AMP level is an important step in the transmission of the effect of various sugars on insulin release; however, glucose and possibly other sugars may also enhance insulin release by additional mechanisms not involving the adenylate cyclase-cyclic AMP system of the beta-cell.

Animals↗
PubMed1976

Decreased cyclic AMP and insulin responses to glucose in pancreatic islets of diabetic Chinese hamsters.

The dose as well as the time kinetics of insulin and adenosine-3',5'-monophosphate (cyclic AMP) responses to glucose were compared in pancreatic islets isolated from normal and diabetic Chinese hamsters. The insulin content in diabetic islets was about one-half that in normal islets. Insulin release in diabetic islets incubated for 10 min with glucose 60-1000 mg/100 ml was from one-third to one-half that in normal islets. Glucose 1000 mg/100 ml stimulated three-fold increases in insulin release without increasing the accumulation of [3H] cyclic AMP in either normal or diabetic islets prelabelled with [3H] adenine. However, in the presence of 1.0 mM of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), glucose 150 mg/100 ml elicited significant increases of insulin release (+ 134%) and [3H] cyclic AMP accumulation in islets (+ 44%) and incubation medium (+ 48%) of islets of normal but not diabetic hamsters. Also, in perifusion experiments with 0.1 mM IBMX, glucose 500 mg/100 ml produced threefold greater increases in insulin release and two-fold greater increases in efflux of cyclic AMP in normal than diabetic islets. By contrast with the lesser effects of glucose in diabetic islets, 1.0 mM IBMX increased islet and medium cyclic AMP, as well as insulin release, similarly in normal and diabetic islets. It is suggested that the impairment of glucose-induced insulin release in islets of the diabetic Chinese hamster may be due to a defective interaction of glucose with the adenylate cyclase-cyclic AMP system in the pancreatic B cell.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Significance of genetic factors for the plasma insulin response to glucose in healthy subjects.

The intravenous glucose tolerance and plasma insulin response to glucose infusion were analysed in a twin and family material, comprising 279 healthy subjects. The relation between the blood glucose and plasma insulin values was studied by an analysis of the principal eigenvalues. The variables obtained were corrected for sex, age and weight, and standardized with regard to mean and variance. The results showed that at least four of the variables have appreciable familial correlations, corresponding to a heritability (h2) varying between 0.38 and 0.72. These correlations could not be accounted for by common environment alone. Thus, the beta cell function in normal man, as measured by a glucose challenge test, appears to be genetically regulated.

Adolescent↗
PubMed1976

Insulin release and cyclic AMP accumulation in response to glucose in pancreatic islets of fed and starved rats.

The dose as well as the time kinetics of insulin and adenosine-3', 5' -monophosphate (cyclic AMP) responses to glucose were compared in pancreatic islets of fed and starved rats. There was a preferential impairment of the early phase of glucose-induced insulin release in perifused islets of rats starved for 16 and 48 h. Similarly, the accumulation of 3H cyclic AMP in islets prelabeled with 3H-2-adenine was less in islets of 48 h starved than fed rats, during the first 10-min of stimulation with 26.7 mM glucose in the presence of 0.1 mM of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, whereas at 30 and 60 min 3H cyclic AMP responses to glucose were similar in fed and starved islets. Also, in 10-min incubations with glucose 3.3, 6.7, 10.0, 13.3, and 26.7 mM without and with 0.1 mM and 1.0 mM 3-isobutyl-1-methylxanthine, insulin release correlated strongly with the accumulation of 3H cyclic AMP in the islets of fed as well as starved rats. The thresholds for glucose-induced insulin and 3H cyclic AMP responses were higher and the maximal responses were lower in starved than fed islets. Preincubation of islets of 48-h starved rats with 16.7 mM glucose for 60 min corrected the impaired insulin and 3H cyclic AMP responses to glucose. Starvation-induced impairment of insulin secretory responses to glucose, and their restoration by preincubation with glucose in vitro, may represent acute regulatory effects of glucose on the adenylate cyclase-cyclic AMP system in the pancreatic beta cell.

Animals↗
PubMed1976

Diminished sensitivity of the insulin response to glucose following growth hormone influsion in man.

The acute effect of growth hormone (GH) administration on the dose-kinetics of glucose-stimulated insulin release was investigated in eight healthy, non-obese male subjects. The glucose-insulin dose-response relationship in these subjects was established by performing glucose infusions at three different dose levels. In a second series of experiments, the glucose infusions were preceded by a 30 min infusion of GH (40 mug/kg body weight), terminated 60 min before administration of glucose. GH induced small but significant reductions in the basal levels of blood glucose and plasma insulin. The glucose tolerance (k-value) was diminished after GH at all glucose doses. Both the initial late phases of insulin response to glucose were impaired following GH treatment. This effect was most pronounced when the intermediary glucose dose (eliciting a blood glucose level around 300 mg/100 ml) was used. Thus, the insulinogenic index (whole period of stimulation) was reduced by GH to 88.9 +/- 7.6, 60.4 +/- 7.1 and 74.3 +/- 11.0% of the respective controls when the smallest, the intermediate, and the largest glucose loads, respectively, were given. The blood glucose-plasma insulin dose-response curves were shifted to the right of the control ones when glucose infusion was preceded by GH. These findings suggest that GH diminishes the sensitivity of the islet for the insulin releasing action of glucose. Some possible mechanisms by which GH may modify insulin release are discussed.

Adult↗
PubMed1976

Potentiation of glucose-induced insulin release by glucose in the isolated pancreas of fed and fasted rats.

Glucose, apart from its acute insulin-releasing effect, exerts a time-dependent potentiating action on subsequent stimulations of the pancreas. The influence of a 24-hour starvation on these two actions of glucose was studied with the completely isolated, perfused rat pancreas preparation. Starvation had no effect on the time kinetics of the insulin response, but the magnitudes of the early and late insulin-secretion phases were reduced to similar extents. It was demonstrated by using a wide glucose concentration range that the maximal insulin response is not significantly modified by starvation. In contrast, both the threshold of stimulation by and the Km for glucose were higher in the pancrease from fasted rats. Thus, starvation reduces the sensitivity of the islet for the insulin-releasing action of glucose. When the stimulatory concentrations of glucose were preceded for 40 minutes by the perfusion of 8.3 mM instead of the basal, 4.4 mM glucose, insulin secretion from the pancreas of fed animals was not modified. In contrast, raising the glucose concentration of the equilibrium period to 8.3 mM potentiated markedly the insulin response to subsequent stimulations in the pancreas from fasted rats. This potentiation expressed itself as increase in the maximal response: the Km for glucose was not reduced. Thus a 40-minute pretreatment with 8.3 mM glucose does not correct the diminished sensitivity induced by a 24-hour starvation. It is concluded that in starvation (1) the sensitivity for glucose of the mechanisms that initiate insulin release is diminished; (2) the sensitivity of the pancreas for the potentiation-inducing action of glucose is augumented. (3) In both respects, the insulin response of fasted rats is similar to that of mildly diabetic subjects. These and other findings suggest that the effect of glucose in initiation of insulin release and on generation of a state of potentiation in the islet are mediated by different mechanisms.

Animals↗
PubMed1975

Effect of phentolamine and preperfusion with glucose on insulin release from the isolated perfused pancreas from fasted and fed rats.

Starvation of rats for 24 hrs resulted in decreased insulin release from the isolated rat pancreas. The effect of fasting could not be counteracted by elevation of the glucose level in the equilibration medium from 0.8 to 1.5 mg/ml. The alpha-adrenergic blocking agent phentolamine (10 mug/ml) stimulated glucose induced insulin release to approximately the same extent in fasted as in fed rats. These findings illustrate the importance of endogenous catecholamines in the regulation of insulin secretion from the isolated pancreas. Our experiments suggest that the impairment of insulin secretion on fasting is due neither to the inhibitory effect of catecholamines nor to the lack of substrate in the pancreas at the initiation of the stimulation.

Animals↗