Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycemia and insulinemia in rat blood samples have been determined at different times before and after administration of glibenclamide, PGE1, glibenclamide and PGE1, glibenclamide and glucose, PGE1 and glucose, and glibenclamide, PGE1 and glucose. PGE1 led to a partial inhibition of glibenclamide induced insulin release, with and without glucose administration, but a total inhibition did not occur. The inhibitory action of PGE1 on insulin secretion was also reflected on the glycemia curves. Defects in insulin release in diabetes could be due in part to an excessive production of PGs, that involve a failure in the beta-cells to respond to glucose signals. The present paper shows that glibenclamide secretory action was not cancelled out by PGE1. These results could explain the availability of glibenclamide in the treatment of diabetes mellitus.
 ...
PMID:[Inhibitory effect of PGE1 on the liberation of insulin induced by glibenclamide]. 393 43

Plasma beta-thromboglobulin was measured, using the Edinburgh radioimmunoassay technique and anticoagulant mixture (containing prostaglandin E1) in 61 normal subjects, 67 diabetics with and 54 diabetics without microangiopathic complications. Plasma beta-thromboglobulin was significantly higher in the diabetic patients (p < 0.01) but there was no significant difference between the two diabetic groups. Twenty-six normal subjects, 27 diabetics with and 39 diabetics without complications were studied further by measuring beta-thromboglobulin in four different ways using two different radioimmunoassay techniques and two anticoagulant mixtures (with and without prostaglandin E1). The Edinburgh assay gave a value 1.97 times that obtained with the Amersham assay, and the Edinburgh anticoagulant a value 0.78 times that with the Amersham anticoagulant. Beta-thromboglobulin concentration in the meniscus layer was approximately twice that in the middle layer. The lower beta-thromboglobulin values obtained with the Edinburgh anticoagulant may result from a different sampling technique or from prevention of in vitro beta-thromboglobulin release, after venepuncture, by prostaglandin E1. Abnormal platelet behaviour in diabetes was confirmed although its role in the pathogenesis of microangiopathic complications remains unclear.
 ...
PMID:Plasma beta-thromboglobulin in diabetes mellitus. 615 42

Aging is characterized by a wide variety of defects, particularly in the cardiovascular and immune systems. Cyclic AMP levels fall, especially in lymphocytes. Delta-6-desaturase (D6D) levels have been found to fall rapidly in the testes and more slowly in the liver in aging rats. D6D is an enzyme which converts cis-linoleic acid to gamma-linolenic acid (GLA). Other factors which inhibit D6D activity are diabetes, alcohol and radiation, all of which may be associated with accelerated aging. In meat eaters or omnivores which can acquire arachidonic acid from food, the main consequences of D6D loss will be deficiencies of GLA, dihomogamma-linolenic acid (DGLA) and prostaglandin (PG) E1. PGE1 activates T lymphocytes, inhibits smooth muscle proliferation and thrombosis, is important in gonadal function and raises cyclic AMP levels in many tissues. It is a good candidate for a key factor lost in aging. Moderate food restriction, the only manoeuvre which consistently slows aging in homoiotherms, raises D6D activity by 300%. Other factors important in regulating D6D and the conversion of GLA to PGE1 are zinc, pyridoxine, ascorbic acid, the pineal hormone, melatonin, and possibly vitamin B3. GLA administration to humans has been found to lower blood pressure and cholesterol, and to cause clinical improvement in patients with Sjogren's syndrome, scleroderma and alcoholism. These diseases are associated with some features of accelerated aging. The proposition that D6D loss is not only a marker of aging but a cause of some of its major manifestations is amenable to experimental test even in humans. The blocked enzyme can be by-passed by giving GLA directly.
 ...
PMID:Loss of delta-6-desaturase activity as a key factor in aging. 627 May 21

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the effect of isoproterenol on adenosine 3',5'-cyclic monophosphate (cAMP) content, inotropy, and phosphorylase activity. Experimental diabetes was induced by intravenous injection of either alloxan (40 mg/kg) or streptozotocin (50 mg/kg). There were no changes in either basal cAMP levels or in isoproterenol-induced cAMP levels in hearts from diabetic rats at either 3 days or 100-120 days after induction of diabetes. Maximum changes produced by isoproterenol in positive and negative dP/dt developments of diabetic rat hearts were also not different from control at either time point. However, phosphorylase was activated to a significantly greater extent by isoproterenol in hearts obtained from acute as well as chronic diabetic rats. Chronic diabetic rat hearts exhibited significantly higher total phosphorylase activity. Diabetic rat hearts had slightly but not significantly higher basal phosphorylase a activity. Furthermore, prostaglandin E1 activated phosphorylase in diabetic rat hearts but not in control rat hearts. Acute metabolic derangements and alterations in Ca2+ homeostasis caused by diabetes could be the underlying causes for this phosphorylase response. Thyroid hormone levels were depressed in diabetic rats. However, hypothyroidism is probably not responsible for the alterations in phosphorylase activity.
 ...
PMID:Effect of experimental diabetes on rat cardiac cAMP, phosphorylase, and inotropy. 630 13

Isolated perfused hearts from normal and alloxan-diabetic rats were studied to determine the effects of prostaglandin E1 (PGE1) on phosphorylase activation in the insulin-deficient state. Perfusion of hearts from normal and diabetic rats with 3 X 10(-5) M PGE1 for the final 2 min resulted in activation to the same extent of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, cAMP-sensitive protein kinase, and phosphorylase kinase. Although phosphorylase activation was somewhat suppressed in both the normal and diabetic heart, PGE1 produced a 36% increase in phosphorylase a in normal hearts and a 44% increase in phosphorylase a in diabetic hearts. The decreased effectiveness of phosphorylase activation by PGE1 appears to be located beyond activation of phosphorylase kinase and perhaps involves an alteration in phosphorylase sensitivity to phosphorylase kinase. Further, the activation of phosphorylase by phosphorylase kinase is hypersensitive in hearts of diabetic rats, perhaps due to a diabetes-related alteration in calcium metabolism.
 ...
PMID:Effects of prostaglandin E1 in diabetic heart. 631 70

Photoelectric plethysmography (PPG) was used to investigate blood flow changes close to superficial subcutaneous injection sites. As a validation procedure, the PPG response to subcutaneous injection of a known hyperemic agent, prostaglandin E1 (10(-5) M), was shown to correlate strongly with subcutaneous blood flow changes estimated by the established technique of 133Xe washout. Changes in blood flow over the subcutaneous injection sites of insulin (Actrapid) and insulin diluent were measured by photoelectric plethysmography in six nondiabetics and in six stable and seven brittle insulin-dependent diabetics. In all subject groups, an acute increase in local blood flow was seen within 2 min of both insulin and diluent injections, probably caused by injection trauma. At diluent injection sites, this acute hyperemia faded rapidly, blood flow returning to preinjection levels within 15-20 min, and there was no further increase in blood flow in any of the subjects. Insulin injected into the nondiabetics and stable diabetics caused a pronounced increase in local blood flow, sustained for at least 60 min after injection. In the brittle diabetics, however, there was no prolonged local hyperemia, the response being significantly less than that seen in both the nondiabetics and the stable diabetics. Insulin-related hyperemia close to injection (or infusion) sites may be important in subcutaneous insulin absorption. Its near-absence in brittle diabetics may contribute to the impaired response to subcutaneous insulin characteristic of these patients.
Diabetes 1983 May
PMID:Changes in blood flow close to subcutaneous insulin injection sites in stable and brittle diabetics. 634 Nov 30

Spleen cells of diabetes-prone BB Wistar rats were found to generate excessively low proliferative responses, and interleukin 2 (IL-2) levels in response to T-dependent mitogens. This abnormality was not due solely to abnormal T cell numbers since: (a) addition of BB spleen cells of BB splenic macrophages to normal major histocompatibility complex (MHC)-matched Wistar Furth (WF) spleen cells resulted in severe suppression of concanavalin A (Con A)-, phytohemagglutinin (PHA)-, and pokeweed mitogen (PWM)-mediated proliferation, and IL-2 production; (b) macrophage depletion from BB spleen cells, but not B cell or T cell depletion, removed completely the suppressive effects of BB cells on WF cells; (c) macrophage depletion greatly enhanced the response of BB lymphocytes to T-dependent mitogens. Although suppressor macrophages could also be found in the spleen of WF control rats they were present in much smaller numbers than in the spleen of BB rats. The suppressive effect of BB macrophages was partially reduced by addition of the prostaglandin synthetase inhibitor indomethacin to cultures. Furthermore, indomethacin (but not catalase or PMA) considerably augmented IL-2 secretion of Con A-stimulated BB spleen cells, but had little effect on WF spleen cells. In contrast, prostaglandins E1 and E2 (PGE1 and PGE2) suppressed IL-2 production. While IL-2 secretion was severely depressed in BB rats unstimulated and lipopolysaccharide (LPS)-stimulated IL-1 secretion by splenic macrophages was normal. BB macrophages did not inactivate IL-2. Low IL-2 production and macrophage-mediated suppression were features of all BB rats tested.
 ...
PMID:Immune dysfunction in diabetes-prone BB rats. Interleukin 2 production and other mitogen-induced responses are suppressed by activated macrophages. 660 15

Prostaglandin E1 was given intraarterially to twenty persons with severe peripheral ischaemia at risk of requiring amputation of a limb for ischaemic ulcers or necrosis. All patients had received conventional therapy without success before PG E1 treatment. An average dose of 6.14 ng/kg/min of PG E1 was given intraarterially for 2 hrs daily over a period of six days. In fifteen cases PG E1 therapy resulted in complete or partial healing of the ulcers and necrotic areas while the patients no longer suffered from pain at rest. No beneficial effects of PG E1 treatment were seen in five patients. In these cases cases multiple arterial occlusions, caused by arteriosclerosis and diabetes mellitus, existed, in more than three levels. Side effects like pain in the infused limb and swelling of the extremity occurred in fourteen patients, but were reversible in each case.
 ...
PMID:[Preliminary results of prostaglandin E1 therapy in peripheral obliterating arteriopathy]. 668 10

Monolayer cultures of neonatal rat pancreatic cells were examined to ascertain whether they synthesize prostaglandin E (PGE) and to determine the effects on insulin secretion caused by PGE and drugs that inhibit its synthesis. PGE release into the medium was observed. Sodium salicylate and ibuprofen (at drug concentrations similar to those achieved therapeutically in humans in vivo) inhibited PGE synthesis in a dose-responsive fashion to a maximum of 70-80% inhibition. Inhibition of PGE synthesis was accompanied by augmented insulin secretion. Both PGE synthesis inhibitors shifted the glucose dose-insulin response curves to the left at low glucose concentrations and augmented maximal insulin release at high glucose concentrations. Increments in glucose-induced insulin secretion induced by sodium salicylate correlated well (r = 0.89) with inhibition of PGE synthesis and addition of exogenous PGE1 to the cultures reversed the augmenting effects of the drug on insulin secretion. It is concluded that cultures of pancreatic cells synthesize PGE and that a function of PGE in these cultures appears to be a tonic negative modulation of glucose-induced insulin secretion.
Diabetes 1981 Jul
PMID:Inhibition of prostaglandin E synthesis augments glucose-induced insulin secretion is cultured pancreas. 701 61

The platelet sensitivity to the antiaggregatory prostaglandins (PGI2, PGE1 and PGD2) was studied in patients with angiographically verified coronary heart disease. The sensitivity was tested in vitro by inhibiting the ADP-induced platelet aggregation by various concentrations of these prostaglandins. Beside the age dependent alterations of platelet sensitivity reported earlier, there is a statistically significant decrease in sensitivity for PGI2 and PGE1 in patients with coronary heart disease. In contrast, no significant change for the PGD2-sensitivity could be observed. In angina pectoris a further significant decrease in sensitivity (again only for PGE1 and PGI2) was found which returned back to the starting values within a few hours. In patients with maturity onset diabetes and coronary heart disease the sensitivity was always lower than in those patients with coronary heart disease alone. Changes in platelet sensitivity might play a key role in initiating and progressing atherosclerosis by an immediate disturbance of hemostatic balance. The studies further support the hypothesis that PGI2 and PGE1 share the same receptor on the platelet surface.
 ...
PMID:Sensitivity of platelets to prostaglandins in cornary heart disease and angina pectoris. 703 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>