Disturbance of pulmonary prostaglandin metabolism in fetuses of alloxan-diabetic rabbits

Tsai, Michael Y.; Schallinger, Luke E.; Josephson, Mark W.; Brown, David M.

doi:10.1016/0005-2760(82)90358-7

Cited by 18 publications

(13 citation statements)

References 16 publications

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“…In the pancreas a possible role for abnormalities of PG metabolism in the pathophysiology of impaired insulin secretion in diabetics has been inferred from the observation that PGE infusion inhibits glucose-induced acute insulin responses in normal human subjects and infusion of sodium salicylate partially restores the acute insulin response to glucose infusion in type II diabetics (48). Similarly, changes in PG metabolism in lung (49)(50)(51), heart (52), and seminal vesicles eluting at 26 min, co-migrated with both 8-HETE and HHT standards in this system. When this peak was collected and injected into a reverse-phase system, it was determined to be entirely HHT.…”

Section: Discussionmentioning

confidence: 99%

Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus.

Schambelan¹,

Blake²,

Sraer³

et al. 1985

J. Clin. Invest.

176

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Abnormalities in glomerular function have been observed frequently in the early stages of both clinical and experimental diabetes mellitus. Because prostaglandins (PGs) are present in the glomerulus and have profound effects on glomerular hemodynamics, and because abnormalities of PG metabolism have been noted in other tissues from diabetics, we studied PG biosynthesis in glomeruli obtained from rats in the early stages of experimental diabetes mellitus. Streptozotocin, 60 mg/kg, was administered intravenously to male Sprague-Dawley rats. Control rats received an equal volume of the vehicle. Glomeruli were isolated 9-23 d later. Production of eicosanoids was determined by two methods: by direct radioimmunoassay after incubation of glomeruli under basal conditions and in the presence of arachidonic acid (C20:4), 30 pM, and by radiometric high-performance liquid chromatography (HPLC) after incubation of glomeruli with ['4C]C20:4. When assessed by radioimmunoassay, mean basal production of both prostaglandin E2 (PGE2) and prostaglandin F2. (PGF2.) was twofold greater in the diabetic animals whereas production of thromboxane B2 (TXB2) was not significantly greater than control. In response to C20:4, both PGE2 and PGF7, were also greater in the diabetic animals, but these differences were not statistically significant. The increased rate of basal PG production did not appear to be related directly to the severity of the diabetic state as reflected by the degree of hyperglycemia at the time of sacrifice. In fact, the rates of glomerular PG production in the individual diabetic animals correlated inversely with the plasma glucose concentration. The increased rate of PG synthesis did not appear to be due to a nonspecific effect of streptozotocin inasmuch as glomerular PG production was not increased significantly in streptozotocin-treated rats which were made euglycemic by insulin therapy. Furthermore, addition of streptozotocin, 1-10 mM, to the incubation media had no effect on PGE2 production by normal glomeruli. PGE2 production by normal glomeruli was also not influenced by varying the glucose concentration in the incubation media over a range of 1-40 mM. When metabolism of I'4C1C20:4 was evaluated by high-performance liquid chromatography conversion to labeled PGE2, PGFu,, TXB2, and hydroxyheptadecatrienoic acid by diabetic glomeruli was two-to threefold greater compared with that in control glomeruli, whereas no significant difference in conversion to 12-and 15-hydroxyeicosatetraenoic acid occurred. These findings indicate that glomerular cyclooxygenase but not lipoxygenase activity was increased in the diabetic animals. A concomitant increase in glomerular phospholipase activity may also have been present to account for the more pronounced differences in PG production noted in the absence of exogenous unlabeled C20:4. These abnormalities in PG biosynthesis by diabetic glomeruli may contribute to the altered glomerular hemodynamics in this pathophysiologic setting.

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Section: Discussionmentioning

confidence: 99%

Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus.

Schambelan¹,

Blake²,

Sraer³

et al. 1985

J. Clin. Invest.

176

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“…Several reports have also strongly suggested that prostaglandins may play important roles in fetal lung maturation (19,22,27). In a previous study (26).…”

Section: Discussionmentioning

confidence: 88%

“…Animals were housed, bred, and treated as previously described (24,27). Female Sprague-Dawley rats (200-250 g; Holtzman, Madison.…”

Section: Anirnu1mentioning

confidence: 99%

“…The second extraction involved acidification of the homogenate with HCI and extraction into diethyl ether (27). Following each of these extractions, the fraction containing 6-keto-PGF,, was dried under nitrogen.…”

Section: Anirnu1mentioning

confidence: 99%

“…Glucocorticoids are also known to inhibit PG synthesis by inhibiting phospholipase A?, an enzyme which makes substrate available by releasing arachidonic acid from phospholipids (7). In fetal lung, the major prostaglandins are PGI, and PGE2 (20,26,27), both of which are vasoactive. In particular, PG12 is a potent vaso- needed to reduce pulmonary vascular resistance (1 1, 12).…”

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Effect of Prenatal Dexamethasone on Immunoreactive 6-Ketoprostaglandin F1α Levels in Fetal Rat Lungs

et al. 1984

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Summaryand bronchodilator, and its presence in an adequate amount isThe effect of prenatal glucocorticoid treatment on levels of immunoreactive 6-ketoprostaglandin F,, (PGF,,) (the stable metabolite of prostacyclin) was studied in fetal rat lungs. During late gestation (20-22 days), levels of 6-keto-PGF,, peaked at 21 days in offspring of control mothers. At a maternal dose of 0.2 mg/kg dexamethasone, maximal enhancement of fetal 6-keto-PGF,, levels occurred at 20 days gestation. At a treatment dose of 0.4 mg/kg, however, dexamethasone increased fetal lung 6-keto-PGF,, concentrations throughout late gestation. Because maturation of fetal lung is known to be delayed in males relative to females, we also studied the impact of sex of the fetus on levels of 6-keto-PGF,,. Our results showed no statistically significant differences between females and males in any of the treatment groups at any of the gestational ages studied. These results suggest that prenatal dexamethasone enhances endogenous levels of 6-keto-PGF,, in fetal rat lungs. Since prostacyclin may play important roles in fetal lung maturation and neonatal lung function, the effectiveness of prenatal glucocorticoid therapy for accelerating functional maturity of the fetal lung may in part be due to stimulation of prostacyclin synthesis. Abbreviations RDS, respiratory distress syndrome PC, prostaglandin RIA, radioimmunoassay TLC, thin layer chromatography HPLC, high performance liquid chromatographyIn recent years, prenatal glucocorticoid therapy has gained increasing acceptance as a means for accelerating fetal lung maturation and reducing the risk of RDS in prematurely born infants (3, 10, 2 1). Studies on possible adverse effects of glucocorticoid therapy, such as its potential for reducing the weight of lung, brain. and other organs, have been reported (8,9). Glucocorticoids are also known to inhibit PG synthesis by inhibiting phospholipase A?, an enzyme which makes substrate available by releasing arachidonic acid from phospholipids (7). In fetal lung, the major prostaglandins are PGI, and PGE2 (20,26,27), both of which are vasoactive. In particular, PG12 is a potent vaso- needed to reduce pulmonary vascular resistance (1 1, 12).Inhibition of prostaglandin synthesis in general and PG12 synthesis in particular, therefore, may cause vasoconstriction which could predispose prematurely born infants to RDS. In addition, diminished PGI, synthesis could complicate or retard the course of recovery of infants with RDS. A previous study in our laboratory. however, showed that prenatal dexamethasone treatment stimulated conversion of ['4C]arachidonic acid to 6-keto-PGF,,, (the stable metabolite of PGI?) in lung homogenates of 20-day fetal rats (26). This may indicate that dexamethasone induced the enzymes of PC12 synthesis in fetal lung. However, since dexamethasone can inhibit prostaglandin synthesis by inhibiting phospholipase A?, isotopic studies of arachidonic acid conversion to prostaglandins in lung homogenates cannot assess the overall effect of dexamethas...

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Impaired awareness of hypoglycaemia: A new risk factor for adverse pregnancy outcomes in type 1 diabetes

Perea

Bertran

Bellart

et al. 2019

Diabetes Metabolism Res

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Aim The aim of this study is to evaluate the impact of impaired awareness of hypoglycaemia (IAH) on metabolic control and pregnancy outcomes in women with type 1 diabetes. Material and Methods This was a single‐centre prospective cohort study of singleton pregnant women with type 1 diabetes. IAH was assessed at the first antenatal visit using Clarke's test (score ≥ 3). Data on metabolic control, hypoglycaemic events, and the lipid profile were collected from prior to pregnancy and in each trimester of gestation. Pregnancy outcomes were also recorded. Results A total of 77 patients with type 1 diabetes were included; 24 (31.2%) were classified as having IAH. Compared with the normal awareness of hypoglycaemia (NAH) group, the IAH group did not show differences in HbA1c, weight gain, insulin doses, or severe and nonsevere hypoglycaemia events throughout pregnancy. IAH was associated with higher triglyceride concentrations in the second trimester (IAH: 154.8 ± 61.1 mg/dL, NAH: 128.6 ± 31.2 mg/dL, P = .034) and an increased risk of neonatal respiratory distress (odds ratio [OR] 11.24; 95% CI, 1.01‐124.9, P = .041) in adjusted models. Increased risk of pre‐eclampsia was related to higher second trimester triglyceride concentrations (OR 1.028; 95% CI, 1.004‐1.053, P = .023) adjusted for confounders. Conclusions The IAH was associated with increased risk of neonatal respiratory distress and pre‐eclampsia, despite showing no differences in metabolic control. Hypoglycaemia awareness in the first antenatal visit should be assessed to identify the subgroup of pregnant women with increased risk of complications.

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Disturbance of pulmonary prostaglandin metabolism in fetuses of alloxan-diabetic rabbits

Cited by 18 publications

References 16 publications

Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus.

Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus.

Effect of Prenatal Dexamethasone on Immunoreactive 6-Ketoprostaglandin F1α Levels in Fetal Rat Lungs

Impaired awareness of hypoglycaemia: A new risk factor for adverse pregnancy outcomes in type 1 diabetes

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