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

This report describes, at least in part, the role of prostaglandin and cyclic nucleotide metabolism in the etiology of the vascular disease associated with diabetes mellitus. Alterations in this metabolism seem associated with induction of platelet aggregation leads to microthromboses leads to microangiopathy sequences that are subtle but inexorable over a long period of time. Prostaglandins are generally elevated in blood from patients having frank signs of diabetic retinopathy when compared with nondiabetic subjects. Prostaglandin concentration remained elevated in diabetic retinopathy patients receiving indomethacin. We formed, therefore, the working hypothesis--yet to be fully tested either in patients or animal models with and without indomethacin treatment--that the increased prostacyclin (synthesized by endothelial microsomes) and cyclic-AMP production, both of which favor prevention of platelet aggregation, accompany the increased concentration of one or more of the prostaglandin E and F compounds. Concurrently, there may be an accompanying reduction of thromboxane A2 (synthesized by platelet microsomes) and cyclic-GMP (both of which favor platelet aggregation) production in the diabetic patients. The elevated prostaglandin in the diabetic patients not receiving indomethacin could possibly be directed toward slowing but not preventing the progression of the complex disease process in diabetes.
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PMID:Proposed metabolic dysfunctions in diabetic microthromboses and microangiopathy. 23 37

A survey is given of the literature on the influence of prostaglandins on the lipid- and carbohydrate metabolism. Some common pathobiochemical features in the development of diabetes mellitus and the ischaemic heart disease are outlined, which became apparent by examinations of the fatty acid pattern in patients. Thus a biochemical basis for that epidemiologically well known fact is given, that diabetes represents a risk factor for the ischaemic heart disease. Some of the latest results from the experimental research suggest that the vascular complications occurring in chronic diabetes are caused by a decrease in the formation of prostacyclin and possibly by an increase in the thromboxane A2 production. Similar changes in the prostaglandin metabolism occur in the ischaemic heart disease and myocardial infarction, too, as experimental results have shown.
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PMID:[Significance of prostaglandins for fat and carbohydrate metabolism with special reference to pathogenesis of diabetes mellitus ]. 36 61

PGE1 has been found to improve the symptoms of diabetic neuropathy. We considered that a PGI2 derivative may also have a similar action and therefore studied its effect in diabetic rats. Iloprost was administered intraperitoneally to streptozotocin-induced diabetic rats at a dose of 10 micrograms/kg/day for a month. The changes in nerve conduction velocity (NCV) were measured in the tail. One day after the last dose of iloprost, both sciatic nerves were removed from each rat, homogenized, and extracted with 6% TCA. The sorbitol and myo-inositol concentrations were determined by a combination of HPLC and an enzymatic method. Cyclic AMP (cAMP) levels were determined by RIA, and Na+, K+ ATPase activity was assessed by the enzyme cycling method of Greene and Lattimer. Iloprost was found to improve the NCV in the diabetic rats. The sorbitol content was not affected by iloprost, but the myo-inositol content was higher in the iloprost group than in the untreated group, although the difference was not statistically significant. The Na+, K+ ATPase activity and cAMP content were significantly higher in the iloprost group than in the untreated group. These findings suggest the possibility that the cAMP-dependent protein kinase (A-kinase) system has an important influence on improvement in Na+, K+ ATPase activity.
Diabetes Res Clin Pract 1992 Nov
PMID:Effect of a prostaglandin I2 derivative (iloprost) on peripheral neuropathy of diabetic rats. 128 52

The synthesis of the prostaglandins (PG) I2 (measured as 6-oxo-PGF1 alpha), E2, E2 alpha) and thromboxane (TX) A2 (measured as TXB2) by the mucosal and muscular portions of the stomach, duodenum, jejunum, ileum, mesenteric vessels, hepatic portal vein and two arteries (carotid and aorta) was investigated in long term streptozotocin-induced diabetes mellitus (DM; fed ad libitum and pair fed). In all regions of the gastrointestinal tract there were no changes in PG synthesis (per unit weight of tissue) in diabetic rats (pair fed or fed ad libitum) compared to controls. However, there were marked increases in PG synthesis (up to 3 fold) by the mesenteric vasculature and hepatic portal vein in diabetic animals fed ad libitum and in pair fed diabetic rats and decreases in the aorta and carotid artery. These data suggest that increases in PG synthesis by the splanchnic vasculature may constitute a specific adaptive response to DM. The similarity of the responses of pair fed rats to those of rats fed ad libitum indicates that DM and not hyperphagia is the likely determinant of these adaptive changes. Given that increased splanchnic blood flow enhances nutrient uptake (both known to occur in DM), the increase in splanchnic vascular PG synthesis, in particular of vasodilatory PGI2, may contribute to enhanced nutrient uptake.
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PMID:Differential changes of prostanoid synthesis by the gastrointestinal tract, mesenteric vasculature and hepatic portal vein of diabetic rats: comparison between pair and ad libitum feeding. 129 14

The aim of this study was to clarify whether or not arachidonic acid metabolic disorders are caused by a substrate inavailability and whether such disorders might contribute to circulatory disturbances in the diabetic myocardium. Norepinephrine induced a decrease in the conductivity of both coronary arterial bed and myocardial microcirculation in alloxan-diabetic dogs. It was markedly (p less than 0.05) attenuated both by indomethacin and acetylsalicylic acid pretreatments indicating an imbalance among the vasoactive prostanoids in diabetes. TXA2 release from the diabetic coronary rings was found to be elevated and could be normalized after the blockade of vascular adrenoceptors by phentolamine (p less than 0.05). PGI2 synthesis was also enhanced by adrenergic blockade in the diabetic arterial rings. After pretreatment with 14C arachidonic acid, in order to measure substrate availability, the arachidonic acid metabolic rate was less in the diabetic coronary arteries than in healty vessels (p less than 0.05). Ten mumol/l norepinephrine decreased arachidonic acid metabolism in the presence of prelabelled substrate in the diabetic animals, compared to an increase observed in metabolically healthy dogs. Therefore diabetes appears to diminish arachidonic acid metabolism and uptake independent of adrenoceptors and to induce an imbalance between vasoconstrictor and vasodilator cyclooxygenase products, resulting in elevated TXA2 release controlled by adrenergic mechanisms which may contribute to an impairment in myocardial microcirculation.
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PMID:Disturbed lipid metabolism in diabetic coronary vessels. 132 Jul 34

Data are presented on the level of stable metabolites of prostacyclin I2-thromboxane A2 system in streptozotocin diabetes mellitus in rats. It is shown that simulation of streptozotocin diabetes mellitus leads to the reduction of 6-ketoprostaglandin F1 alpha content in the aortal wall tissue and blood plasma, and to a rise of thromboxane B2 level and the thromboxane B2/6-ketoprostaglandin F1 alpha ratio in the blood plasma. Inclusion of docosahexaenic and eicosapentaenic acid concentrate into the ration of animals with streptozotocin diabetes mellitus is conducive to normalization of the stable metabolite level in the prostacyclin I2-thromboxane A2 system.
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PMID:[Effects of docosahexaenoic and eicosapentaenoic acids on the state of metabolites of the prostacyclin I2--thromboxane A2 system in streptozotocin diabetes mellitus]. 138 92

Glomerular filtration rate, renal plasma flow, renal tubular sodium reabsorption (derived from lithium clearance) and renal excretion rates of kallikrein, prostaglandin E2 and systemic and renally-derived metabolites of prostacyclin and thromboxane A2 were measured in patients with Type 1 (insulin-dependent) diabetes mellitus and in normal subjects. Diabetic patients with glomerular hyperfiltration had greater active kallikrein and prostaglandin E2 excretion than patients with normal glomerular filtration rate or than normal control subjects. Both active kallikrein and prostaglandin E2 excretion correlated directly with glomerular filtration rate. Active kallikrein excretion correlated directly with the reabsorption of sodium in the distal tubule. The excretion rates of 6-keto prostaglandin F1 alpha, 2,3 dinor 6-keto prostaglandin F1 alpha, thromboxane B2, 2,3 dinor thromboxane B2 and 11-dehydro thromboxane B2 excretion were not different between the groups. This study confirms in man our previous finding of increased renal kallikrein production in the hyperfiltering streptozotocin-diabetic rat model. Given that kinins generated by kallikrein are extremely potent vasodilators and stimulate the renal production of eicosanoids that also regulate glomerular function, our findings suggest that increased kallikrein activity and prostaglandin E2 production may contribute to renal vasodilatation and hyperfiltration in human diabetes. The localization of kallikrein in the distal connecting tubule makes it plausible that altered sodium transport in the distal tubule may be a signal to increase generation of kallikrein.
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PMID:Renal excretion of kallikrein and eicosanoids in patients with type 1 (insulin-dependent) diabetes mellitus. Relationship to glomerular and tubular function. 139 81

Increased thromboxane A2 (TXA2) generation by platelets has been reported both in diabetic patients and streptozocin-induced diabetic rats. This increase is in contrast to the decreased prostacyclin (PGI2) synthesis by endothelial cells in diabetes. An imbalance in the ratio of TXA2/PGI2 has been implicated in increased platelet aggregation and a high incidence of vascular disease in human diabetes. The mechanism for this imbalance, however, remains elusive. In a previous study from our laboratory, we reported unchanged arachidonic acid levels in platelet membrane phospholipids of 3-week diabetic rats, but a decreased arachidonic acid level in platelet membrane phospholipids of 6-week diabetic rats. In the present communication, we report the role of enzymes that are involved in remodeling arachidonic acid levels of platelet membrane phospholipids in both 3- and 6-week diabetic rats. No alterations were observed in the activities of arachidonoyl-CoA synthetase, acyl-CoA: lysophosphatidylcholine acyltransferase, or phospholipase A2 in platelets from both 3- and 6-week diabetic rats. However, both increased uptake and incorporation of [14C]arachidonic acid into platelets were observed in the diabetic platelet-rich plasma. In conclusion, increased TXA2 formation in diabetic platelets is not due to alterations in the activities of enzymes involved in the incorporation into or release of arachidonate from the diabetic platelet membrane phospholipid, but may be due to increased efficiency of uptake, incorporation or possibly redistribution of this fatty acid among phospholipid classes in diabetic platelets.
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PMID:Modifications of platelet phospholipid fatty acid composition in streptozocin-induced diabetic rats. 143 63

In pregnant women with severe diabetes mellitus, intrauterine growth retardation (IUGR) may occur despite hyperglycemia. Uterine blood flow may be an important factor in this process. Using pregnant streptozotocin-induced diabetic rats (pregnant STZ-diabetic rats), we evaluated functional and morphological changes in the endothelium, as well as platelet thromboxane A2 (TXA) production and their influence on uterine blood flow. Decreased basal endothelial prostacyclin (PGI2) production as well as significant attenuation of the production response to stimulus was noted, suggesting an impairment of PGI2 production. In the platelet, TXA2 production was augmented, leading to a hypercoagulable state. Decreased myometrial blood flow was documented. Scanning electron microscopy (SEM) revealed definite morphological abnormality of the endothelial cells, probably affecting the permeability to molecules, a major endothelial function. Based on these data, the endothelial derangements suggested by SEM and arachidonic acid metabolism alterations may affect fetal growth in the severe pregnant diabetic through alterations in uterine blood flow.
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PMID:Vascular wall arachidonic acid metabolism and fetal growth in the pregnant STZ-induced diabetic rat. 144 26

In one third of patients who suffered an infarction NIDDM and arterial hypertension are present. In the absolute majority of patients with IHD, as apparent from the IRI and C-peptide response after a glucose load, hyperinsulinism is present. The blood sugar response can have the character of diabetes or of impaired glucose tolerance, the curve may be very flat or normal while the IRI and C-peptide response are excessive. Hyperinsulinism has a hypersecretory origin as suggested by the concurrently elevated C-peptide level but also reduced insulin utilization in the liver and peripheral target organs. Hyperinsulinism is thus a regular associated phenomenon of IHD and is a special risk factor independent on hyperglycaemia and associates with the other main risk factors of IHD such as arterial hypertension, HPLP (android obesity), hyperglycaemia (NIDDM) and hirsutism as a manifestation of a hyperandrogenic state in the female organism with the syndrome of polycystic ovaries. Hyperinsulinism plays an indirect role in the pathogenesis of coronary syndrome via the main risk factors (5H syndrome--hyperinsulinism, hypertension, HPLP, hyperglycaemia, hirsutism) and also directly by its action on endothelial paracrine mechanism of the coronary circulation where in the early stage vasoconstrictor factors predominate (endothelin-1, PGF2-alpha) over physiological vasodilatating factors (EDRF-NO, PGE2, PGI2) and this leads then to functional spasms. It seems that also the coronary X syndrome develops very frequently on the background of the hormonal metabolic X syndrome or the 5H syndrome.
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PMID:[Hyperinsulinism and the coronary syndrome]. 149 68


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