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

The carrageenin-induced foot oedema in rats is considerably decreased by insulin pretreatment, but increased in alloxan diabetes. Maximum inhibition by insulin occurs in the early phase of the oedema reaction and the insulin action is even further increased when it is administered 30 min after carrageenin. Doses of insulin as low as 1 U/kg intravenously produce significant inhibition. Determinations of the components of the kinin system indicate that the kininogenase activity is increased, and both the kininogen and kininase content are in turn decreased in the plasma of insulin-treated animals. When the carrageenin-induced oedema fluid of the paw after insulin is analysed for kininogen and kininase, their levels are significantly decreased when compared with those of oedema fluid without insulin. Histamine content in the oedema fluid is significantly enhanced by insulin. The anti-inflammatory effect of insulin under these conditions therefore appears to involve changes in the kinin system.
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PMID:Involvement of the kinin system in the insulin-induced inhibition of carrageenin oedema in rats. 91 16

Sprague-Dawley rats were separated in 4 groups. G1 received streptozotocin (ST). G2 received nicotinamide (NC) followed by ST. G3 was a NC control and G4 was a citrate control. The rats were sacrificed after 28 h and the islets isolated. Histamine and histaminase were determined. In the islets there was an increase in histamine content in G1 and a smaller increase in G2. The first two groups differ significantly and also in relation to the control groups. A decrease in islet histaminase does not seem responsible for the increased histamine, since group 2 (NC + ST) which had no diabetes, had a lower activity than group 1 (ST). It is suggested that histamine liberation by ST may be related to the diabetogenic effect of this drug.
Diabetes Res Clin Pract
PMID:Early increase in histamine concentration in the islets of Langerhans isolated from rats made diabetic with streptozotocin. 170 Nov 17

Clinical and experimental diabetes are associated with an increased number of mast cells and elevated tissue histamine concentrations. This study compared histamine release from peritoneal mast cells derived from diabetic and control rats. Experimental diabetes was induced by a single i.v. injection of streptozotocin (50 mg/kg body weight). Measurement of plasma glucose levels confirmed the diabetic state. Peritoneal mast cells were stimulated for 10 min with the lectin concanavalin A (0.5-100 micrograms/ml) in the presence or absence of phosphatidylserine, clinical dextran (0.6-1200 micrograms/ml) in the presence of phosphatidylserine, the calcium ionophore A23187 (0.1-1 microM) or the basic releasing agent compound 48/80 (0.1-10 micrograms/ml). Histamine release induced by these agents was similar in both populations. Further studies will compare the differences in histamine release from mast cells isolated from different tissues, e.g. heart and lung. In addition, physiological stimuli which are altered in the diabetic state (e.g. hyperosmolalar solutions and free radical generating systems) are under investigation.
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PMID:Comparison of histamine release from peritoneal mast cells derived from diabetic and control rats. 171 32

To test the hypothesis that histamine receptors mediate increased blood-retinal barrier permeability in experimental diabetes, 51 rats were made diabetic by streptozocin injection (65 mg/kg; jugular vein) and were held for four weeks. The seven animal groups were as follows: untreated controls; untreated diabetic rats; diabetic rats receiving diphenhydramine hydrochloride (Benadryl); diabetic rats receiving cimetidine hydrochloride (Tagamet); diabetic rats receiving diphenhydramine and cimetidine; diabetic rats receiving purified pork insulin (Iletin II); and diabetic rats receiving insulin and diphenhydramine. All treatments were given during the last week. Blood-retinal barrier permeability was assessed through measurement of the vitreous content of fluorescein isothiocyanate conjugated to bovine serum albumin (FITCBSA) after 20 minutes of FITCBSA circulation. Vitreous FITCBSA content of the diabetic group was 64% greater than control content. Diabetic rats treated with either diphenhydramine or diphenhydramine and insulin had respective decreases of 43% and 40% in vitreous FITCBSA content. The vitreous content of the diabetic group receiving insulin was lowered 37% below untreated diabetic values, while the vitreous FITCBSA content of the diabetic group receiving both insulin and diphenhydramine was reduced 63%. These data indicate that retinal histamine H1-receptor activation may be partially responsible for initial blood-retinal barrier leakage of macromolecules into the vitreous and that this abnormal leakage can be prevented both by diphenhydramine and by insulin. Histamine H1 receptors may play an important role in mediating increased blood-retinal barrier permeability in experimental diabetes.
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PMID:Histamine H1 receptors mediate increased blood-retinal barrier permeability in experimental diabetes. 252 87

Histamine (HA) metabolism in the brain of mice with streptozotocin (STZ)-induced diabetes was examined. The levels of tele-methylhistamine (t-MH), a major metabolite of brain HA, significantly increased 3 and 4 weeks after STZ injection. However, the HA turnover rates in the diabetic mice, determined from the accumulation of t-MH after the administration of pargyline, were not different from the control values when the animals were allowed free access to food. When the mice were starved for 15 h 4 weeks after STZ treatment, the brain levels of L-histidine decreased significantly, whereas HA turnover increased significantly. Such changes were not observed in starved control mice. Histidine decarboxylase or HA N-methyltransferase activity did not change after starvation in either diabetic or control mice. These results show that the histaminergic (HAergic) activity in the brains of diabetic mice remains within normal range as long as the animals are allowed free access to food. However, they also indicate that a marked enhancement of HAergic activity accompanied by a decrease in the brain L-histidine level occurs in starved diabetic mice.
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PMID:Changes in histamine metabolism in the brains of mice with streptozotocin-induced diabetes. 270 9

We have investigated the uptake of histamine by human platelets. Incubations were carried out in platelet rich plasma prepared by using sodium citrate as an anticoagulant at histamine concentrations of 2.5 nmol X 1(-1), with and without stirring, in a platelet aggregometer cuvette at 37 degrees C. Stirring increased platelet histamine uptake significantly. Conventional platelet aggregating agents (e.g. adrenaline) significantly increased platelet histamine uptake at sub-aggregatory concentrations. Histamine uptake by platelets may be a useful index of platelet behaviour when studying the effect of subaggregatory concentrations of platelet agonists in conditions where platelet aggregation is altered, e.g. peripheral vascular disease and diabetes mellitus.
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PMID:Histamine uptake by human platelets. 311 59

Since histamine has recently been shown to play an important role in the pathogenesis of atherosclerosis in experimental nonketotic diabetes, and since leukocytes and platelets contain most of the histamine in blood, we have determined the levels of histamine in these cells from patients with peripheral vascular disease (PVD), insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). The leukocyte and platelet histamine concentration in PVDs was significantly greater than that in controls, IDDMs and NIDDMs. Histamine content of leukocytes and platelets from IDDMs and NIDDMs did not differ from that in control subjects. The higher histamine content of leukocytes and platelets in PVD may lead to a greater release of this amine at sites of vascular endothelial damage. Increased histamine release may increase endothelial permeability and contribute to further vascular injury as observed in experimental models of diabetes and hypercholesterolemia.
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PMID:Increased histamine content in leukocytes and platelets of patients with peripheral vascular disease. 335 68

Microvessels in the cheek pouch of the hamster were investigated to determine their structural, reactivity, and permeability characteristics after the induction of diabetes. To induce diabetes, hamsters were injected with streptozotocin (50 mg/kg body wt./day, i.p., for 3 days). Vehicle-injected, age-matched hamsters were the controls. Diabetic hamsters were characterized by elevated serum glucose (greater than 300 mg/dl) and triglycerides and decreased serum insulin (50%). Microvascular studies were completed on cheek pouch microvessels suffused with Ringer's solution (37 degrees C, pH 7.4) bubbled with 95% N2-5% CO2. Vascular dimensions and reactivity of selected arterioles and venules to microapplications of norepinephrine were determined with a video micrometer using intravital microscopy. Restrictiveness of the microvascular membranes to fluorescein-labeled dextran fractions (mol wt: 150,000; 40,000; 20,000 daltons) was measured by determining the number of leaky sites. Stimulation of membrane permeability by histamine was investigated. There were no major alterations in arteriolar lumen and wall diameters, whereas venular lumen diameters were increased in hamsters diabetic for two months. Likewise, arteriolar responses to norepinephrine were not altered by diabetes; however, venular responses were decreased at two months. The restrictiveness of the vascular membrane to various dextran fractions was dramatically decreased in the diabetic animals at two months. Histamine did not alter microvascular leakage in the diabetic as it did in the normal hamsters. These studies indicate that microvascular alterations, venular dilation, and increased permeability to large molecules occur in the diabetic hamster within two months after the induction of diabetes.
Diabetes 1981 Feb
PMID:Microvascular alterations develop in Syrian hamsters after the induction of diabetes mellitus by streptozotocin. 616 95

The response to vasoactive agents of microvessels in situ and large arteries in vitro was compared in normal and alloxan-diabetic rats. Noradrenaline was equally effective in evoking a constrictor response of mesenteric microvessels in normal and diabetic animals. The constrictor response to a standard amount of noradrenaline in such vessels was fully antagonized by acetylcholine or papaverine, the minimum effective doses being equivalent in normal and diabetic animals. In contrast, the minimum doses of histamine or bradykinin, effective in normal animals, had to be increased about 20 fold to be active in diabetic animals. Increased osmolarity of extracellular fluid caused a significant and equivalent increase in latency of the vasoconstrictor response of microvessels to noradrenaline in normal and diabetic animals. Concentration-effect curves, constructed from the response of isolated aortae to noradrenaline, were similar in normal and diabetic animals, provided the endothelium was removed. Diabetes only affected preparations in which the endothelium was left intact. In these, the median effective concentrations of noradrenaline were greatly increased in comparison with normal values. Precontracted aortae from normal and diabetic animals were equally relaxed by acetylcholine and histamine, provided the endothelium was left intact. Loss of the relaxant response of the preparations in all groups of animals was observed following removal of endothelial cells. It is suggested that different mechanisms may be involved in the effects of vasodilator agents on large arteries in vitro or small vessels in situ. Histamine and bradykinin which are potent permeability-increasing factors, may antagonize the vasoconstrictor response of microvessels to noradrenaline through an action on endothelial cells with increased vascular permeability and temporary changes in composition of extracellular fluid. The reactive process of endothelial cells to permeability factors was affected by diabetes mellitus. However, the response of microvessels to acetylcholine and papaverine which are devoid of permeability-increasing properties, was not influenced by diabetes.
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PMID:Vascular reactivity in diabetes mellitus: role of the endothelial cell. 665 56

1 Noradrenaline (NA) evoked a vasoconstrictor response in rat mesenteric microvessels in situ, the latency and nature of which was analogous in normal and alloxan-diabetic animals.2 Histamine and bradykinin (Bk) were capable of antagonizing the response to NA in normal but not in diabetic animals. In contrast, acetylcholine (ACh) was equally effective as an antagonist to NA in both groups of animals.3 The altered responses to histamine and Bk were not associated with hyperglycaemia since fasting rendered the diabetic animals normoglycaemic and yet did not restore the reactivity of microvessels. Previous administration of insulin to diabetic animals corrected the impaired responses to histamine and Bk.4 A similar condition of impaired responses to histamine and Bk was produced in normal animals by the intravenous injection of 2-deoxyglucose although ACh remained fully active.5 Apparently, the functional changes observed in the response to histamine or Bk, as antagonists of the vasoconstrictor reaction to NA, were not associated with a defective response of all smooth muscle. First, because ACh remained active in diabetic animals, and, second, because extravascular smooth muscles obtained from either normal or diabetic rats were equally relaxed by histamine or Bk in vitro.6 It is suggested that histamine and Bk antagonized the vasoconstrictor response of microvessels to NA through an action on lining endothelial cells resulting in increased vascular permeability and hyperosmolarity of extracellular fluids.7 The process depended on the availability of insulin, and, therefore, might be affected by intracellular glucopaenia as occurring in diabetes.8 Intracellular glucopaenia markedly affected other structures. Reduced atria rates were observed in diabetes, despite the fact that the isolated preparation responded normally to NA, ACh or tyramine. Partial substitution of glucose in the bathing fluid by 2-deoxyglucose or addition of NaF to the organ bath evoked similar changes in atria from normal animals.9 ACh which has little effect on vascular permeability must exert its vasodilator effects through mechanisms which are different from those influenced by the biochemical changes occurring in diabetes.
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PMID:Influence of diabetes on the reactivity of mesenteric microvessels to histamine, bradykinin and acetylcholine. 682 15


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