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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

6.1. It is known from the literature that in diabetes mellitus there is an increased tendency for the thrombocytes to aggregate. This fact represents a risk of thrombosis supplementary to the vascular wall lesions which develop in the course of this disease. An inhibition of platelet aggregation such as has recently been obse3rved in vitro under the influence of beta-cytotropic sulphonylureas (tolbutamide, glicalazide), must therefore be regarded as an additional, desired quality of action of these agents. 6.2. In an attempt to throw more light on this subject studies were conducted to discover whether an inhibition of platelet aggregation can be regarded as a basic property of all beta-cytotropic antidiabetic agents and whether dissociation exists between this property and the hypoglycemic effect. The possible existence of evidence for identical or similar sites of action of sulphonylureas on the control system of the thrombocytes, beta-cells and the liver was also investigated, the main point of interest being whether sulphonylurea derivatives exert their effects via the adenylate cyclase -cAMP-system. The thrombocytes were also used to discover whteher ss-cytotropic antidiabetic agents, such as non-steroidal antiphlogistic compounds, inhibit the synthesis of aggregation-promoting prostaglandins (PGE2). 6.3. The influence on adenosine diphosphate (ADP)-induced thrombocyte aggregation has been dtudied in vitro with platelet rich rat plasma (PRP) using a turbidimetric method. Preliminary studies have also been conducted with PRP obtained after previous treatment of the donor animals...
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PMID:[Mechanisms of platelet aggregation inhibition caused by sulfonylurea compounds. 4. Discussion, summary, and literature]. 16 7

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.
Diabetes 1975 Aug
PMID:Decreased cyclic AMP and insulin response to glucose in isolated islets of neonatal rats. 16 74

1. Epinephrine-induced increase in rat liver cyclic AMP in vivo was potentiated when the circulating insulin was suppressed by injection of anti-insulin serum or by induction of diabetes. Consequently, phosphorylase was activated, glycogen synthetase was inactivated and glycogen accumulation induced by glucose load was prevented by epinephrine in the insulin-deficient rats to a much larger extent than in normal rats. 2. Insulin lack was effective in potentiating epinephrine-induced increase in liver and muscule cyclic AMP even after the treatment of rats with theophylline; the potentiation could not be solely accounted for by the inhibition of cyclic AMP phosphodiesterase. Thus, it is likely that insulin lack enhaces epinephrine activation of adenylate cyclase. 3. Unlike epinephrine, glucagon increased liver cyclic AMP to essentially the same extent whether the rat was treated with anti-insulin serum or not. 4. Based on the difference in dose-response curves between normal and insulin-deficient rats, a possibility is discussed that there are two adenylate cylase in the liver with higher and lower affinities for epinephrine and that circulating insulin blocks the high affinity enzyme selectively.
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PMID:Attenuation of epinephrine-induced increase in liver cyclic AMP by endogeneous insulin in vivo. 18 27

The effects of insulin and adrenaline on cyclic AMP (cAMP) levels in diaphragms of normal, streptozotocin-diabetic and insulin-treated diabetic rats were studied. Adrenaline caused a biphasic rise in cAMP with peak values of cAMP within the first few minutes. Diaphragms of diabetic rats showed an increased responsiveness to adrenaline. Injection of insulin to diabetic rats normalized the rise in cAMP after addition of adrenaline. There was no difference in basal levels of cAMP between diaphragms of normal, diabetic or insulin-treated diabetic rats. Insulin in vitro did not affect basal cAMP-levels or the release of cAMP from the tissue but significantly decreased adrenaline-induced peak levels of cAMP. This effect of insulin was abolished by theophylline. The results of the present study suggest that experimental diabetes is associated with changes of the adenylate cyclase and/or phosphodiesterase enzyme activities in skeletal muscle resulting in an increased responsiveness to adrenaline. Since insulin in vitro depressed the adrenaline-induced elevation of cAMP the increased responsiveness in diaphragms of diabetic rats might be attributed to the specific lack of insulin.
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PMID:Effect of insulin and adrenaline on cyclic AMP in the diaphragm of normal and diabetic rats. 19 69

Incubation of pancreatic islets of fed rats at glucose 10 and 15 mM induced a rapid rise of the islet cyclic adenosine 3',5'-monophosphate (cAMP) content. Maximum levels were attained at 15 min and lasted until 30 min, after which cAMP declined again. Insulin secretion increased most rapidly from 15 min onward, i.e. after the rapid rise of cAMP. Islet cAMP at either 15 or 30 min showed its major concentration-dependent increase between glucose 7.5 and 10 mM. Glucose 15 mM did not further enhance the cAMP response, although this concentration increased insulin secretion more than two-fold over values observed at glucose 10 mM. Thus, the glucose dose-response relations for cAMP levels and insulin secretion appear to be different, indicating that factors other than cAMP alone determine the secretory response to glucose. Fasting for 24 and 72 h progressively inhibited glucose-induced insulin secretion. At glucose 15 mM the secretory inhibition disappeared after 30-45 min, but at glucose 10 mM it persisted for at least 90 min. Increasing periods of fasting also progressively delayed and inhibited the cAMP response to glucose, most strongly at glucose 10 mM. Fasting for 24 h shifted the glucose dose-response curves for cAMP and insulin secretion to the right, but the maximum responses at glucose 37.5 mM were not significantly inhibited. The secretory inhibition appeared to be linearly related with the cAMP content in two different ways: (a) At fixed concentrations of glucose, the increasing of the cAMP response (at 15 min) as induced by 24 and 72 h of fasting correlated with the secretory inhibition over the initial 30 min. (b) At one fixed period of fasting (24 h), the variable percent inhibition of the cAMP response to graded concentrations of glucose (5-37.5 mM) correlated with the percent secretory inhibition at these concentrations. These correlations were no longer apparent after 30 min of incubation. The results support the view that inhibition of the adenylate cyclase-cAMP system is a major determinant factor in fasting-induced impairment of insulin secretion during the initial 30 min of glucose stimulation.
Diabetes 1979 Feb
PMID:Insulin secretion and cyclic adenosine 3', 5'-monophosphate levels in pancreatic islets of fed and fasted rats. Time course and dose kinetics during glucose stimulation. 21 91

Somatostatin's release from the isolated rat pancreas was studied using a perfusion technique. Arginine at a concentration of 19 mM produced a biphasic increase in somatostatin release from the perfused rat pancreas. Both first and second phases of somatostatin's increase are significantly higher in the presence of 1 mM theophylline than in the absence of the drug. These results indicate the possible inclusion of the adenylate cyclase--cyclic AMP system in the regulatory mechanism of rat pancreatic somatostatin secretion.
Diabetes 1979 May
PMID:Theophylline: potentiation of arginine-induced somatostatin release from the isolated rat pancreas. 43 74

Rats treated chronically with dopamine receptor blockers were found to have an increase in striatal 3H-dopamine binding and adenylate cyclase activity as manifestations of receptor supersensitivity. Both the increase in binding and in adenylate cyclase activity were reversed by chronic 1-dopa treatment, presumably by increasing the supply of specific ligand (dopamine). The use of deliberate receptor sensitivity manipulation may be useful as a treatment for conditions involving disturbances in receptor sensitivity such as tardive dyskinesia and insulin resistant diabetes.
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PMID:Reversal of two manifestations of dopamine receptor supersensitivity by administration of L-dopa. 84 96

We examined changes in guanosine triphosphate-dependent signal transduction mechanisms in the retina from the early stages of the streptozotocin-diabetic rat, a model for Type 1 (insulin-dependent) diabetes mellitus. Guanosine triphosphate binding, guanosine triphosphatase activity, and binding of (azido) guanosine triphosphate decreased significantly in the retina as early as 2 weeks after the induction of diabetes. The ability of guanosine triphosphate to inhibit forskolin-stimulatable adenyl cyclase was also abolished. These data suggest functional deterioration of G-proteins, especially Gi, in diabetic retina. Further studies using retinal rod outer segments revealed deterioration in light-sensitive, guanosine triphosphate-dependent functions of transducin in diabetic rats. Pertussis toxin-catalysed ADP ribosylation of the alpha subunit of transducin, a heterotrimeric G-protein of rod outer segments, was also reduced in diabetes. No functional effects were seen in purified subunits of transducin subjected to non-enzymatic glycation in vitro. On the other hand, incubation of non-diabetic rod outer segments with (12-0-tetradeconyl) phorbol-13-acetate, a protein kinase C agonist, in the presence of magnesium and adenosine triphosphate resulted in the reduction of guanosine triphosphate-binding and hydrolysis, thus indicating that protein kinase C may be involved in the regulation of these activities. The significance of these observations in the early visual abnormalities associated with diabetes is discussed.
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PMID:Functional alterations of G-proteins in diabetic rat retina: a possible explanation for the early visual abnormalities in diabetes mellitus. 132 50

The specific activity of Na(+)-K(+)-ATPase in the renal medulla and cortex of 50-day-old streptozotocin (STZ)-induced diabetic mice was increased 58% and 50%, respectively, as compared to controls. Km values of Na+ and K+ for this enzyme were unaltered, while that of ATP was decreased in diabetic mice. The Na(+)-K(+)-ATPase in control medulla and cortex was activated by both cholera and pertussis toxins, while this effect was abolished in diabetics. Since dibutyryl cAMP stimulates cortical Na(+)-K(+)-ATPase activity in control mice, the activation effect of cholera toxin on this enzyme might be due to its interaction with a Gs-protein and the persistent stimulation of adenylate cyclase activity, while the effect of pertussis toxin might be due to its masking of the inhibitory action of a Gi-protein on adenylate cyclase activity. However, the protein kinase C (PKC)-associated Na(+)-K(+)-ATPase might also be quiescent in diabetes, because the stimulating effect of phorbol 12,13-dibutyrate (PDBu) and phorbol 12-myristate 13-acetate (PMA) on this enzyme was abolished in diabetic cortex. In addition, nicardipine and ouabain were found to have differential effects on this enzyme derived from control and diabetic mice.
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PMID:Differentiation of renal Na(+)-K(+)-ATPase in control and streptozotocin-induced diabetic mice by G-protein acting toxins and phorbol esters. 132 74

The effect of diabetes mellitus on beta-adrenergic receptor number (B(max)), receptor-cyclase coupling and adenylate cyclase (AC) activity was determined in cerebral microvessels isolated from control and streptozotocin induced diabetic rats after 5 weeks of induction of diabetes. Scatchard analysis of [125I]iodocyanopindolol (ICYP) binding indicated that the B(max) (fmol/mg) in diabetic rat cerebral microvessels (63.8 +/- 4.8) (mean +/- S.E.M.) was not significantly different from the B(max) in control rats (56.5 +/- 6.9). Isoproterenol competition of [125I]ICYP binding sites indicated that the percentage of beta-receptors expressing high affinity binding was 53.9 +/- 0.45% in control rats and 47.5 +/- 2.3% in diabetic rats. The total isoproterenol-stimulated AC activity (pmol cAMP/mg) in diabetic rats (76.7 +/- 6.1) was significantly lower than that in control rats (118.4 +/- 11.2) (P less than 0.01). However, the net isoproterenol-stimulated AC activity (i.e. total minus GTP-stimulated AC activity) was not altered in diabetes. The net sodium fluoride (NaF) stimulated AC activity in diabetic rats (109.5 +/- 11.4) was significantly lower than the control rats (154.3 +/- 16.3) (P less than 0.05). It is concluded that diabetes mellitus in rats is associated with reduced post receptor activation of adenylate cyclase in cerebral microvessels while the beta-adrenergic receptor density, affinity and receptor-cyclase coupling are not significantly altered.
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PMID:Beta-adrenergic receptor activity of cerebral microvessels in experimental diabetes mellitus. 132 92


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