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V Grill

Publications and source records attributed to V Grill.

At least 217 records · Page 12Linked 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↗
PubMed1977

Cyclic AMP and insulin release.

The role of cyclic adenosine-3',5'-monophosphate (cAMP) for insulin secretion has been investigated. In isolated islets of Langerhans from the rat, glucose increases cAMP concomitant with insulin secretion. Stimulation of these two parameters is likewise reversible in parallel. The minimal and maximal concentrations of glucose eliciting cAMP and insulin responses are similar. Isomers and epimers of glucose influence insulin and cAMP in a parallel fashion as do sulfonylurea compounds (tolbutamide and glibenclamide). On the contrary, the time-dependent potentiation of glucose-induced insulin secretion is not accompanied by gross changes in cAMP. Reciprocally, in the absence of glucose islet cAMP can be markedly elevated by other agents (methyl xanthines, cholera toxin) without major insulin responses. The results indicate that metabolism of cAMP in the beta-cell is intimately linked to the glucose (and sulfonylurea) action on insulin secretion, although other factors influenced by the hexose are also necessary for the release process. The finding that the cAMP response is impaired in fasting, during the neonatal period and in diabetes mellitus (in the Chinese hamster) suggests an important role for the nucleotide in physiological and pathophysiological states characterized by decreased insulin release.

Animals↗
PubMed1977

Studies on the mechanisms of somatostatin action on insulin release. IV. effect of somatostatin on cyclic AMP levels and phosphodiesterase activity in isolated rat pancreatic islets.

The effects of somatostatin on insulin release and cyclic AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Ceoncentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cyclic AMP accumulation induced by 16.7 mM glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H]cyclic AMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H]cyclic AMP accumulation induced by the phosphodiesterase inhibitor, IBMX, while no inhibition was seen, again in the absence of hexose, when the [3H]cyclic AMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30%. It is suggested that somatostatin-induced inhibition of insulin release is, at least partially, mediated by cyclic AMP, probably through an action on islet adenyl cyclase.

Adenylyl Cyclases↗
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

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↗
PubMed1975

Dynamics of alpha-adrenergic inhibition of the adenyl cyclase-cyclic amp system in human adipose tissue.

In short-term incubations of fat cells isolated from human adipose tissue, noradrenaline (0.2-2x10--5 M), a mixed alpha and beta-adrenergic agonist, stimulated only slightly cyclic AMP accumulation. In the presence of the alpha-adrenergic blocking agent phentolamine (0.05-5mug/ml), noradrenaline markedly augmented the amount of labelled cyclic nucleotide. The stiumlatory effect of noradrenaline and noradrenaline plus phentolamine was abolished by propranolol (0.1-10 mug/ml). Theophylline (10--4-10--3 M) slightly increased the (3-H) cyclic AMP levels per se and magnified the stiumulatory action of other agents, but did not mimic the potentiating effect of phentolamine on noradrenaline action.

Adenylyl Cyclases↗
PubMed1975

Accumulation of cyclic AMP in hypothyroidism. Decreased sensitivity to norepinephrine in rat adipocytes.

The effect of hypothyroidism on the noradrenaline-induced accumulation of 3H-cyclic-AMP was measured in rat epididymal adipose tissue. Adipocytes from hypothyroid animals showed a decreased response to noradrenaline 0.02-0.2 times 10-5 m, while higher concentrations of the catecholamine seemed to elicit the same response in cells obtained from euthyroid or hypothyroid animals. The diminished sensitivity to noradrenaline was unaltered after the addition of phentolamine. It is suggested that thyroid hormones modulate the catecholamine-induced lipolytic response at least partly through the adenyl cyclase cyclic-AMP system.

Adipose Tissue↗
PubMed1975

Decreased cyclic AMP and insulin response to glucose in isolated islets of neonatal rats.

The (3H) cyclic AMP accumulation was measured in incubations of pancreatic islets from one-day, six-day, and thirty-five-day-old rats exposed to a low (0.6 mg./ml.) or a high (3.0 mg./ml.) glucose concentration with or without the addition of 0.1 mM. of the phosphodiesterase inhibitor 3-isobutyl- 1 -methylxanthine (IBMX). In the thirty-five-day-old rats, (3H) cyclic AMP accumulation was significantly enhanced after sixty minutes' incubation in a high glucose concentration and further increased by IBMX. These changes were paralleled by a stimulated insulin release, measured simultaneously. By contrast, in the one-day-old rats, no effect of glucose with or without IBMX was seen on (3H) cyclic AMP, while the minor insulin release due to high glucose alone was markedly potentiated by IBMX. Even in the presence of this agent the insulin response to glucose was, however, clearly inferior to that seen in the thirty-five-day-old animals. The stimulatory patterns of glucose-induced insulin release in the six-day-old animals was intermediate between the other two age groups. At this age, stimulation of (3H) cyclic AMP due to glucose was observed only in the presence of IBMX. Measurement of (3H) cyclic AMP after three minutes' incubation confirmed these different stimulatory patterns of glucose in the age groups studied. It is suggested that the inefficiency of glucose to stimulate the adenyl cyclase-cyclic AMP system of the beta cell from fetal and neonatal animals may be one important factor determining the insensitivity to the insulin-releasing action of glucose that exists at this stage of development.

Adenylyl Cyclases↗
PubMedDate not supplied

Previous exposure to glucose enhances insulin and suppresses glucagon responses to arginine in man.

UNLABELLED: The effects of previous exposure to glucose on the insulin, glucagon, growth hormone and blood glucose responses to subsequent stimulation with L-arginine were investigated in normal man. During control conditions (i.e., after 120 min of saline infusion), the i.v. administration of arginine enhanced the release of all three hormones and caused a small and transient rise in blood glucose. When arginine was preceded by i.v. glucose during 0-60 min, followed by a 'rest period' of 60-120 min, the insulin release induced by the amino acid was further enhanced, glucagon and GH release were unaffected and blood glucose depressed below control levels. When arginine was preceded by a small oral glucose load (0.5 g/kg) the initial insulin response to arginine was augmented, the initial glucagon response was slightly but significantly depressed and blood glucose lowered while the growth hormone response was unaffected. CONCLUSIONS: (1) a near-physiological intake of glucose increases insulin and depresses glucagon secretion evoked by amino acids resulting in increased glucose disposal; (2) the modifications of the insulin and glucagon responses constitute separate components in the feed-back regulation of glucose homeostasis.

Adult↗
PubMedDate not supplied

Gentamicin ototoxicity: histological and ultrastructural alterations after transtympanic administration.

The histological and ultrastructural appearances of the inner ear vestibulum were studied after transtympanic administration of gentamicin in guinea-pigs. The animals were treated with a single transtympanic dose (0.2 cm3) of 4% gentamicin sulphate solution in the right ear; the left one was considered as control. After 7 days they were sacrificed and the vestibula of both inner ears were removed to be examined both by light and electron microscopy. In the treated inner ear damage was not always evident at light microscopical level, even if a case of complete disepithelialization of cristae ampullares was found. The examination by TEM revealed evident damage in the vestibular non-sensorial cells, such as severe cellular vacuolation, whereas sensorial elements presented heterochromatinic thickenings and cytoplasmic wrinkling, as compared to controls. The tunica fibrosa presented an irregular fibrillar plot, as well as that of the myelinic lamellae in the vestibular nerve fibres.

Animals↗