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)

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
 ...
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

Prostaglandin E2 (PGE2) production by superfused glomeruli from rats made diabetic for 2 wk by streptozocin injection is twofold higher than that by glomeruli from normal rats. The higher rates of PGE2 production by glomeruli from diabetic rats are associated with higher levels of labeled free arachidonate in glomeruli prelabeled with [3H]arachidonate, both basally and after stimulation with Ca2+ ionophore A23187. The difference between release of labeled arachidonate from phospholipids of diabetic versus normal glomeruli is likely underestimated by measurements of arachidonate alone due to more rapid incorporation of released arachidonate into triacylglycerol of diabetic glomeruli. A23187 induced a fall in labeled phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol in glomeruli that had been prelabeled with [3H]arachidonate and also induced a reduction in the mass of these phospholipids. Consistent with the higher levels of labeled arachidonate, the reduction in both labeled phospholipids and phospholipid mass with A23187 was greater in glomeruli from diabetic than normal rats. Furthermore, the reduction in labeled phospholipids and phospholipid mass with A23187 was largely (62-80%) accounted for by a fall in phosphatidylcholine plus phosphatidylethanolamine in glomeruli from both normal and diabetic rats. These results suggest a primary role for phospholipase A2 in A23187 actions on glomerular arachidonate release in normal rats and for the higher levels of arachidonate found in glomeruli from diabetic rats. Nevertheless, A23187 also stimulated the production of inositol phosphates--a measure of cellular phospholipase C activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Apr
PMID:Role of enhanced arachidonate availability through phospholipase A2 pathway in mediation of increased prostaglandin synthesis by glomeruli from diabetic rats. 313 11

A rat model combining two-kidney, one-clip (2K1C) renovascular hypertension and streptozotocin-induced diabetes mellitus was used to assess the pathogenetic significance of vasodilator prostaglandins in diabetic glomerular injury. Glomeruli isolated from normotensive diabetic rats produced greater than normal amounts of PGE2 and 6-keto PGF1 alpha under in vitro incubation conditions. In 2K1C hypertensive-diabetic rats, glomeruli from unclipped kidneys (which are prone to accelerated diabetic glomerular injury) produced similarly elevated amounts of PGE2 and 6-keto PGF1 alpha, which significantly exceeded the levels produced by glomeruli from clipped kidneys (which are relatively protected from glomerular injury), despite exposure to a similar diabetic environment. In contrast, glomeruli from both unclipped and clipped kidneys of 2K1C hypertensive-non-diabetic rats produced normal amounts of PGE2 and 6-keto PGF1 alpha. These results suggests a correlation between vasodilator prostaglandin metabolism and susceptibility to diabetic glomerular injury, and illustrate that enhanced glomerular prostaglandin production is not an invariable metabolic consequence of hyperglycemia or insulin deficiency. The data also demonstrate that hemodynamic as well as metabolic factors may influence glomerular prostaglandin metabolism in experimental diabetes mellitus.
 ...
PMID:Glomerular prostaglandin production in diabetic rats with renovascular hypertension. 316 82

Normal pregnancy in women and rats is characterized by an increased glomerular filtration rate. Because prostaglandin glomerular synthesis has been reported to be increased in 2 other circumstances with glomerular hyperfiltration (streptozotocin-induced diabetes and high protein dietary intake in Heymann nephrilis), we studied prostaglandin biosynthesis in glomeruli obtained from pregnant Wistar rats in comparison with non pregnant rats during the estrus cycle. Comparatively to the 3 first phases of the cycle, and wether or not arachidonic acid was present, PGE2 and PGF2 alpha production rates were found significantly higher in diestrus 2 (2-3 fold increase for both) at 15 days of pregnancy (2 fold increase for PGE2, 5-6 fold increase for PGF2 alpha) and at 21 days of pregnancy (5-6 fold increase for both). On the other hand synthesis of TXB2 was not increased during pregnancy nor during diestrus 2. Plasma renin activity (PRA) was increased during pregnancy. It is concluded that in presence of increased PRA, the increased synthesis of PGE2 may be the hormonal factor explaining, at least in part, the hemodynamic mechanism of glomerular hyperfiltration which has been previously described by micropuncture techniques and characterized by increased renal plasma flow, increased glomerular filtration pressure and decreased ultrafiltration coefficient.
 ...
PMID:Effect of pregnancy on plasma renin activity and glomerular synthesis of prostaglandins and thromboxane in rats. 332 5

Some studies have recently reported increased production of platelet thromboxane and decreased vascular prostacyclin in patients with diabetes mellitus. The impact of these changes on platelet and vascular functions in vivo is still speculative. Using radio-immunoassay and high pressure liquid chromatography we have studied the plasma levels of 6-keto-PGF1 alpha, TXB2 and PGE2 in 23 juvenile-onset diabetics. There was no significant difference in these plasma prostaglandins between the diabetics and a control group. The prostaglandins were neither correlated to blood-glucose nor the degree of glycosylation (HbA1c). Our results can not support the hypothesis that decreased vascular prostacyclin and increased platelet production of TXB2 are important factors in diabetic patients.
 ...
PMID:Plasma prostaglandins: 6-keto-PGF1 alpha, TXB2 and PGE2 in juvenile-onset diabetes determined by high-pressure liquid chromatography and radio-immunoassay. 346 Jan 2

To study prostaglandin (PG) metabolism in children with insulin-dependent diabetes mellitus, plasma levels of PGE2, PGF2 alpha, and thromboxane B2 and the composition of serum fatty acids were measured. Platelet aggregation, a risk factor in diabetic vascular complications, was also measured. The mean levels of plasma PGE2 and PGF2 alpha were high and serum dihomo-gamma-linolenic acid and arachidonic acid were low in the diabetic children. The plasma thromboxane B2 levels of the diabetic children and normal controls were not significantly different. Platelet aggregation was also increased in diabetic patients. These results suggest that the insulin deficiency and high blood sugar in diabetic children may disturb the supply of dihomo-gamma-linolenic acid from cis-linoleic acid, decreasing prostaglandin formation in series 1. Then feedback regulation may increase production of PGE2 and PGF2 alpha in series 2. Altered PG metabolism may be responsible for the occurrence and progression of vascular complications in the diabetic children.
 ...
PMID:Prostaglandin metabolism in children with diabetes mellitus. I. Plasma prostaglandin E2, F2 alpha, TXB2, and serum fatty acid levels. 346 55

Studies were conducted to determine whether prostaglandins are added to the urine during its passage through the rat urinary bladder in vivo. Control rats and rats with chronic streptozotocin-induced diabetes were anesthetized with Inactin, 100 mg/kg i.p., and urine was collected simultaneously from both kidneys. Urine from the left kidney was collected directly from the renal pelvis via a ureteral cannula, while urine from the right kidney was collected via a cannula in the urinary bladder. Prostaglandins in the urine were measured by radioimmunoassay. No difference in urinary concentration or rate of excretion of 6-keto-PGF1 alpha or PGE2 was seen between ureteral urine and bladder urine from either normal or diabetic rats. The results of this study indicate that in vivo there is no intralumenal addition of either 6-keto-PGF1 alpha or PGE2 to the urine by the ureteral bladder of rats.
 ...
PMID:6-Keto-prostaglandin F1 alpha is not added to urine during passage through the rat urinary bladder in vivo. 346 93

Urinary prostaglandin (PG) and thromboxane (Tx) excretion, measured by radioimmunoassay, were examined in two groups of male Wistar rats made diabetic with streptozotocin, 70 mg/kg, one of which received daily insulin beginning on the 7th day after administration of streptozotocin. In addition, urinary kallikrein excretion and blood pressure were monitored. After the induction of diabetes the profile of urinary eicosanoid excretion was altered. 6-keto-PGF1 alpha and TxB2 excretion increased markedly within 24 to 48 hr and remained elevated for the duration of the study, up to 58 days. PGF2 alpha excretion also increased, the change being apparent after 6 days whereas PGE2 excretion was reduced at this time. Urinary kallikrein excretion was unchanged but blood pressure became elevated above control levels 2 weeks after the induction of diabetes. Insulin treatment, to maintain mean blood glucose levels below 200 mg/dl, resulted in decreased excretion of TxB2, PGF2 alpha and 6-keto-PGF1 alpha. However, excretion of PGE2 and kallikrein were increased after insulin treatment which also prevented the elevation in blood pressure. These studies indicate that insulin treatment of experimental diabetes corrects alterations in renal arachidonic acid metabolism and prevents the associated increase in blood pressure.
 ...
PMID:Influence of insulin on urinary eicosanoid excretion in rats with experimental diabetes mellitus. 352 18

Prostaglandin (PG) E2 binding to fat cells and its consequent antilipolytic effect have been studied in experiments using laboratory animals, but no binding studies have yet been reported using adipocytes from humans. Consequently, we have characterized PGE2 binding to human isolated fat cells to compare the apparent binding constant to the IC50 for the antilipolytic effect of PGE2. Our data indicate that human fat cells contain binding sites that specifically recognize prostaglandins of the E series and demonstrate stereospecific recognition of the more potent of two 15-methyl-PGE2 analogues. There was no evidence for rapid metabolism of PGE2 by isolated adipocytes such as occurs in lung and liver tissue. A double-reciprocal plot of binding data obtained at saturation using [3H]PGE2 and increasing concentrations of PGE2 indicated a single class of binding sites with an apparent binding constant (0.54 nM) that agreed well with the IC50 (0.26 nM) for the antilipolytic effect of PGE2 we observed in human fat cells. The findings from these binding and lipolysis studies are in general agreement with published observations using adipocytes from rodents and provide evidence that the conclusions reached from previous studies of laboratory animals are relevant to adipocyte physiology in humans.
Diabetes 1985 Feb
PMID:Characterization of prostaglandin E2 binding to isolated human adipocytes. 385 1

In a randomized double-blind study we evaluated the effects on cervical ripening and labor induction of 0.5 mg PGE2 in gel given intracervically and 2.0 mg PGE2 given as a vaginal suppository. All patients were at term with unfavorable cervical scores. The indications for induction were toxemia, diabetes mellitus, Rh-immunization, or intrauterine growth retardation. Significantly better results for both cervical priming and labor induction were obtained after intracervical PGE2-gel application than after treatment with placebo or vaginal suppositories. Eleven out of 19 patients (58%) were delivered within 24 h after intracervical PGE2-gel compared to two out of 19 patients given placebo (p less than 0.01). In patients not delivered 24 h after the start of treatment, the mean cervical score had changed from 3.7 to 6.0 (p less than 0.05) after PGE2-gel application compared to a change from 3.9 to 4.3 after placebo treatment (n.s.). The outcome after treatment with PGE2 suppositories did not differ significantly from that with placebo treatment. In a subsequent study 25 patients were given 0.5 mg PGE2-gel intracervically. The results were consistent with those obtained in patients receiving PGE2-gel intracervically in the double-blind study. Few side effects were noted. No patient complained of gastro-intestinal discomfort but increased myometrial activity was observed in two patients; one after placebo and the other after active intracervical PGE2-gel treatment. The hyperactivity was readily countered with the beta 2-agonist, terbutaline. All infants were born in good condition with Apgar scores of 7 or more within 5 min. At pediatric examinations at 1 week and at 6 months of age all children seemed healthy.
 ...
PMID:Intracervical versus intravaginal PGE2 for induction of labor at term in patients with an unfavorable cervix. 386 Nov 38


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