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

Treatment of non-insulin-dependent diabetes mellitus patients with nephropathy of the nephrotic type using 40 micrograms prostaglandin E1 given intravenously twice daily for 4 weeks reduced the urinary protein concentration. Prostaglandin E1 also increased the total serum protein and serum albumin concentrations, and reduced creatinine clearance and plasma renin activity following frusemide loading. Treatment with the prostaglandin did not, however, significantly affect the blood urea nitrogen and the serum creatinine concentration. It is concluded that prostaglandin E1 has overt effects on diabetic nephropathy.
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PMID:Influence of prostaglandin E1 on heavy proteinuria in slightly azotaemic diabetics. 186 54

To understand the effects of diabetes on vascular smooth muscle function and the underlying mechanism(s) involved, we examined the responses to alpha-adrenoceptor agents, serotonin (5-HT), K+, and prostaglandins in the carotid artery of male New Zealand white rabbits with chronic diabetes (16 weeks) induced chemically by alloxan (100 mg/kg, intravenously) treatment. Isolated ring segments of diabetic rabbit carotid artery exhibited an increased (20-60%) maximal response to norepinephrine (NE), methoxamine, phenylephrine, and K+ as compared with controls. Responses to 5-HT were not significantly increased. Nevertheless, there were no significant differences in ED50 values of the agonists in either of the groups. Putatively selective alpha 2-adrenoceptor agonists (clonidine and guanabenz), prostaglandin E1 (PGE1) and prostaglandin I2 (PGI2) did not elicit any response in control vessels. In the diabetic state, however, these drugs contracted the artery in a dose-dependent fashion. Isoproterenol (0.1-10 microM) relaxed arterial rings previously contracted with all the agonists except PGE1 and PGI2, which were potentiated by isoproterenol. Contractions to PGE1 or PGI2 alone or in the presence of isoproterenol were reduced or abolished by 10(-5) M phentolamine. Under these conditions, isoproterenol exhibited its typical relaxatory action. Nifedipine was more potent in inhibiting the K+ response in diabetic carotid artery than in the controls. These results suggest an increased reactivity of diabetic rabbit carotid artery to alpha 2-adrenoceptor agonists, K+, PGE1, and PGI2 which may, at least in part, be due to an increased sensitivity of calcium channels in diabetic vessels. Contractile responses to PGE1 and PGI2 could be attributed to their action on adrenergic neurotransmission, thereby facilitating the release of NE from presynaptic nerve terminals. Furthermore, isoproterenol at a high dose (1 microM or more) may directly stimulate alpha-adrenoceptors. Whether or not this effect of isoproterenol is only prostaglandin-dependent is not clear.
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PMID:Effect of chronic experimental diabetes on vascular smooth muscle function in rabbit carotid artery. 243 41

The effect of diabetes on vascular smooth muscle function was investigated in the muscular arteries from spontaneously and chemically induced diabetic rats. Isolated ring segments of superior mesenteric arteries from BB diabetic and streptozotocin (STZ)-diabetic rats (12 weeks after onset of diabetes) were used for isometric tension studies. Contractile responses to alpha-adrenoceptor agonists (norepinephrine, methoxamine, phenylephrine, B-HT 920, guanabenz, SKF 89748-A), serotonin, and K+ were significantly higher in STZ-diabetic rat arteries as compared with the controls. In spontaneously diabetic rat arteries only the contractile responses to the putatively selective alpha 2-adrenoceptor agonists, K+ and prostaglandin E1, were significantly increased. pD2 values of the agonists in both groups of diabetic arteries were not significantly different from the respective controls. Nifedipine inhibited all contractile responses in a dose-dependent fashion. The responses to K+ and alpha 2-adrenoceptor agonists were attenuated to a greater extent by nifedipine in both groups of diabetic blood vessels. The calcium channel activator, BAY K 8644, produced a twofold increase in force of contraction in streptozotocin-diabetic and spontaneously diabetic rat arteries as compared with the responses in their respective controls. These results suggest caution in extrapolating all the findings from the streptozocin-induced diabetic model to the spontaneously diabetic model. However, increased activity of calcium channels in vascular muscle cells in both groups of diabetics may be responsible, at least in part, for the increased vascular contractility in diabetes mellitus.
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PMID:Vascular responses to agonists in rat mesenteric artery from diabetic rats. 244 21

The effect of a newly developed oral agent, prostaglandin E1 (PGE1) analogue TFC 612, on diabetic neuropathy was studied by giving it for 6 wk to streptozocin-induced diabetic rats that had been diabetic for 3 mo and was compared with the effects of aldose reductase inhibitor ONO 2235. Although both compounds improved decreased motor nerve conduction velocity, the effect of TFC 612 continued during the 6 wk of treatment, whereas that of ONO 2235 became weaker from wk 4. The abnormality in sciatic nerve sorbitol and myo-inositol levels was reversed with ONO 2235, whereas it was unchanged with TFC 612. With the laser Doppler flowmetry technique, a decrease in the sciatic nerve blood flow in diabetic rats was shown to improve with both compounds, but TFC 612 had a greater effect than ONO 2235, and the increased lactate level of the diabetic nerve was corrected with both compounds, suggesting that both may be associated with the amelioration of ischemia in the diabetic endoneurium. Both TFC 612 and ONO 2235 partially but significantly normalized decreased fiber size in diabetic rats. On the other hand, TFC 612 completely normalized the dilated lumen area in diabetic rats, whereas ONO 2235 did not. These results suggest that the PGE1 analogue TFC 612 has a significant effect on diabetic neuropathy, possibly via vasotropic action, and may be a potent compound for the treatment of diabetic neuropathy.
Diabetes 1989 Jul
PMID:Effect of prostaglandin E1 analogue TFC 612 on diabetic neuropathy in streptozocin-induced diabetic rats. Comparison with aldose reductase inhibitor ONO 2235. 252 92

The addition of prostaglandin I2 (PGI2) enhanced the adhesion of red cells from normals and patients with diabetes mellitus or sickle cell anemia (SCA) to human cultured endothelial cells (p less than 0.025). The maximal effect was reached with 10(-11) M PGI2 after 30 min incubation. Red cell adhesion was also increased by PGD2 but PGE1 and 6-keto-PGF1 alpha had no significant effect. Since enhanced adhesion of red cell to endothelium and increased red cell calcium content have been proposed to be related in SCA, we have investigated the calcium binding to human resealed normal erythrocyte membrane by using (45Ca) calcium in presence of the different PG which alter red cell adhesion or not. Calcium binding was time-dependent and potentiated in presence of PGI2 (p less than 0.01) but not of PGD2. The fact that erythrocyte adhesion is enhanced by both PGI2 and PGD2 while calcium binding is increased only by PGI2 suggests that the two phenomenon can be dissociated.
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PMID:Modification of membrane properties of erythrocytes by PGI2. 267 83

To determine whether the urinary albumin excretion rate (UAER) could be reduced without adversely affecting renal function, prostaglandin E1 (PGE1) was administrated to Type 2 (non-insulin-dependent) diabetic patients with both high and low microalbuminuria, who were matched for age, weight, height and hemoglobin A1c levels. The study was performed as a randomized double-blind trial, with the patients receiving either PGE1 or placebo. In patients who initially had a UAER above 30 mug/min (high UAER group), the UAER was significantly (p less than 0.01) reduced by the administration of PGE1. In this group the UAER after stopping PGE1 administration was comparable to baseline values. During PGE1 administration in the high UAER group, the filtration fraction (FF) was significantly reduced (p less than 0.01) while the glomerular filtration rate (GFR) was unchanged. In patients with an initial UAER below 30 mug/min (low UAER group) the UAER was not altered during the administration of PGE1. In this low UAER group both the FF and GFR remained unchanged. The urinary beta2-microglobulin excretion rate did not change significantly during the administration of PGE1 in either group. These results suggest that the decreased UAER in patients with an abnormally high albumin excretion, may be due to a change in the glomerular permeability to albumin related to a decreased FF.
Diabetes Res 1989 Mar
PMID:Renal effects of prostaglandin E1 in type 2 (non-insulin-dependent) diabetic patients with subclinical nephropathy. 268 Feb 26

The effect of dihomogammalinolenic acid (DHLA) administration on platelet aggregation and prostaglandin production, erythrocyte fatty acid composition and serum lipids was compared in healthy subjects and insulin-dependent diabetics (IDDs). In healthy subjects, DHLA caused a significant inhibition of ADP-induced platelet aggregation and an increase in platelet PGE1 release; IDDs did not show these changes. There were no differences, however, in platelet thromboxane A2 (TXA2) or PGE2 release between healthy subjects and IDDs before and after DHLA. Following DHLA, the arachidonic acid content of erythrocytes increased in healthy subjects; this increase was not observed in IDDs. DHLA induced a significant fall in serum non-esterified fatty acid concentrations in both groups without altering either cholesterol or triglyceride concentrations. These data show for the first time that IDD platelets may have a specific defect of PGE1 synthesis quite distinct from the delta 5- and delta 6-desaturase defects known to be associated with experimental diabetes; this defect may contribute to platelet hyper-aggregability in diabetes; and DHLA has a potent antilipolytic effect in vivo; and erythrocytes from IDDs may have a delta 6-desaturase defect.
Diabetes Res 1986 Jan
PMID:The effect of dihomogammalinolenic acid on platelet aggregation and prostaglandin release, erythrocyte membrane fatty acids and serum lipids: evidence for defects in PGE1 synthesis and delta 5-desaturase activity in insulin-dependent diabetics. 293 1

Spontaneous changes in isometric developed tension (IDT) as a function of time after isolation (contractile constancy) in uteri from control-castrated and castrated chronic streptozotocin-diabetic rats, were explored. The effects of injecting 17-beta estradiol (Eo) were also studied. No differences in the minor changes of contractile constancy, between control and diabetic preparations, during a period of 60 min, were detected, whereas uteri from non-diabetic Eo injected animals (0.5 + 1.0 ug, prior to sacrifice), exhibited a profound reduction of IDT, significantly greater than in tissues obtained from Eo injected-diabetic rats. Moreover, basal generation and outputs into the suspending solution of prostaglandins (PGs) E1, E2 and F2 alpha, were explored in the same groups, at 60 min following tissue isolation. The basal outputs of these three PGs were similar in castrated control rats, but preparations from castrated-diabetics released significantly more PGE1. The administration of Eo to castrated-diabetics, failed to alter the releases of the three PGs explored. In addition, the metabolism of labelled arachidonic acid (AA) into different prostanoids (6-keto-PGF1, PGF2, PGE2 and thromboxane B2-TXB2), was also investigated. The non-diabetic spayed rat uterus converted AA into these four prostanoids, the transformation into 6-keto-PGF1 alpha (as an index of PGI2 formation) being the most prominent. In preparations from diabetic rats the formation) being the most prominent. In preparations from diabetic rats the formation of 6-keto-PGF1 alpha, PGF2 alpha and PGE2, was significantly smaller than in controls, whereas a greater % of TXB2 formation (as an index of TXA2), was detected. On the other hand uterine preparations from non-diabetic spayed rats injected with Eo formed less 6-keto-PGF1 alpha and PGE2 and similar amounts of PGF2 alpha or of TXB2 from AA, than Eo injected controls, whereas uteri from castrated diabetic animals injected with Eo, formed a similar % of 6-keto-PGF1 alpha, PGF2 alpha and PGE2 from AA, than tissue preparations from non-estrogenized controls. However, the enhanced transformation of the labelled fatty acid precursor (AA) into TXB2 in the diabetic group, was significantly reduced by the steroid. The role of the augmented generation and release of PGE1 in uteri from diabetic rats is discussed in terms of precedents indicating the relevance of PGs type E supporting rat uterine motility. In addition the influence of Eo is attractive, because its reducing effect on TX production, in diabetes, a disease known to be accompanied by enhanced synthesis of vasoconstrictor and platelet aggregation TXA2, and by frequent obstructive circulat
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PMID:Effects of experimental diabetes on spontaneous contractions, on the output of prostaglandins and on the metabolism of labelled arachidonic acid, in uteri isolated from ovariectomized rats. Influences of estradiol. 312 57

A new prostaglandin E1 analogue (TFC-612) was orally given to streptozocin-diabetic rats for 4 weeks after the induction of diabetes and its effects on motor nerve conduction velocity were studied. The compound significantly prevented a decrease of the velocity but did not reverse abnormal sorbitol and myo-inositol contents of the sciatic nerve. The results suggest that TFC-612 has a potent effect on diabetic nerve dysfunction via other mechanism than the correction of sorbitol and myo-inositol metabolisms and could be a potential compound for therapy of diabetic polyneuropathy.
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PMID:A new prostaglandin E1 analogue (TFC-612) prevents a decrease in motor nerve conduction velocity in streptozocin-diabetic rats. 327 9

Platelet sensitivity to antiaggregatory prostaglandins (PGI2, PGE1, PGD2) was studied in 143 patients (122 male) with angiographically proven peripheral vascular disease and compared with age-matched clinically normal controls. Patients had a significantly lower platelet sensitivity to PGI2, PGE1, and PGD2 than controls. Clinical stages had no significant influence on the platelet sensitivity to PGI2 and PGE1. Patients with stage IIa had a lower sensitivity to PGD2 than patients with stage IV, the difference not being significant. Analyzing the influence of risk factors like diabetes, hyperlipoproteinemia, or smoking, there seemed to be an inverse relation between risk factors and platelet sensitivity to PGI2 and PGE1. Smokers especially, together with smokers exhibiting an additional risk factor, exhibited the highest prostaglandin consumption (PGI2, PGE1) and therefore the lowest platelet sensitivity. However, it has to be emphasized that the differences were not significant. There was a significant correlation between platelet sensitivity to PGI2 and PGE1, whereas this was not the case between the respective sensitivities to PGI2 and PGD2. This supports the hypothesis that both these prostaglandins (PGI2, PGE1) share the same receptor on the platelet surface, whereas PGD2 has its own receptor.
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PMID:Platelet sensitivity to antiaggregatory prostaglandins (PGE1,D2,I2) in patients with peripheral vascular disease. 388 23


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