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)

The main difference between normal and streptozotocic rat fed a diet, supplied during 35 days, including (as 1.5 g oil for 100 g diet) either naudicelle oil (with gamma-linolenic acid), either sunflower oil (without gamma-linolenic acid), or naudicelle oil + peanut oil, is that there are more non esterified fatty acids in streptozotocic livers. This result supports the view that liver phospholipids are more labile or that there is an important release of fat, even if we do not observe an increase of streptozotocic rat plasmatic non esterified fatty acids. Comparing normal and streptozotocic rat we found interesting results about fatty acids liver lipids composition: non esterified fatty acids are particularly rich in polyunsaturated fatty acids, mainly in linoleic and arachidonic acids, in diabetic rat. These results contribute to explain, to some extent, the important catabolism of polyunsaturated fatty acids in the diabetic rat, as they may reveal an increased activity of phospholipase A2 in this kind of animal. Naudicelle oil in the diet is, in our experiment, without favourable results on the amount of different lipidic classes and their fatty-acids composition, into liver and plasma of the streptozotocic rat, comparatively to the rat administered with sunflower oil; this may be explain by the fact that gamma-linolenic acid was in restricted amount in the diet and that its own conversion was partially inhibited by diabetes.
 ...
PMID:[Effect of supplementation with gamma-linolenic acid on the fatty acid composition of lipids from the liver and plasma in the diabetic rat]. 620 5

Fatty acid incorporation into specific phospholipids of isolated islets of the rat was investigated using unsaturated [14C]arachidonic acid. Glucose (25 mM) stimulated the incorporation of arachidonic acid into phosphatidylinositol (PI) and phosphatidylcholine (PC) in a time-related manner correlated with two phases of insulin release. Arachidonate incorporation was inhibited by calcium deprivation. The sulfonylurea tolbutamide stimulated an early monophasic release of insulin that was accompanied by increased [14C]arachidonate incorporation into PI and PC. The cholinergic agonist and insulin secretagogue, carbamylcholine, also promoted the incorporation of [14C]arachidonate into PI/phosphatidylserine (PS) and PC fractions. 2-Deoxy-D-glucose, which does not support insulin release, did not enhance arachidonate incorporation into phospholipids. However, phenylephrine, an inhibitor of glucose-induced insulin secretion, stimulated arachidonate turnover in PI. p-Bromophenacyl bromide, an inhibitor of phospholipase A2, markedly depressed both glucose-stimulated arachidonate incorporation into phospholipids and insulin release. The stimulated release of arachidonate from endogenous radiolabeled phospholipids provided additional evidence that phospholipase A2 mediates glucose stimulation. However, since glucose also promoted the incorporation of saturated [14C]palmitic acid into PE (phosphatidylethanolamine) and PI/PS fractions, a phospholipase A1 may also mediate the glucose response. Thus, fatty acid incorporation into islet phospholipids mediates the effects of various secretagogues on insulin release. However, the ability of phenylephrine to stimulate arachidonyl PI turnover suggests that fatty acid turnover is not a sufficient stimulus for release. Augmented levels of unsaturated fatty acids in islet cell membranes may promote fusion or activate enzymes important for hormone release.
Diabetes 1983 Jan
PMID:Fatty acid incorporation into phospholipids of isolated pancreatic islets of the rat. Relationship to insulin release. 633 3

Although exogenous prostaglandins are recognized modulators of insulin secretion, the relationship between their endogenous synthesis and insulin secretion has not been rigorously studied in isolated adult rat islets. Using 3H-arachidonic acid as a tracer, we evaluated the effect of glucose stimulation upon the incorporation of this fatty acid into islet phospholipids and prostaglandins (separated by extraction and sequential silicic acid, thin-layer and paper chromatography). We observed that 3H-arachidonic acid was incorporated into islet phospholipids and prostaglandins under basal conditions (0.3 mg/ml glucose). Furthermore, exposure of islets to a stimulatory glucose concentration led to significant increases in the recovery of 3H-arachidonic acid-derived radioactivity in islet phosphatidylethanolamine, phosphatidylserine, sphingomyelin, and phosphatidylinositol as well as into all of the measured prostaglandins (A2, B2, D2, E2, and F2 alpha). The most marked increases in recovered radioactivity resulting from a stimulatory glucose concentration were in islet phosphatidylethanolamine and prostaglandin A2 (which we believe to be derived, in large part, from endogenously synthesized prostaglandin E2). These glucose-induced increases in 3H-arachidonic acid-derived radioactivity in both the phospholipid and the prostaglandin fractions were eliminated by the inhibition of phospholipase A2 activity with mepacrine or by the inhibition of cyclooxygenase activity with sodium salicylate. When islets prelabeled with 3H-arachidonic acid were exposed to a high glucose concentration in a perifusion system, there was a brisk extracellular release of radioactivity (presumably representing unidentified prostaglandins) that began within 1 min and that peaked slightly before the peak of the first phase of insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1983 Jun
PMID:Endogenous prostaglandin synthesis and glucose-induced insulin secretion from the adult rat pancreatic islet. 635 79

We have studied the effect of streptozotocin (SZ)-induced diabetes on fatty acyltransferase and phospholipase enzyme activities involved in the synthesis and degradation of rat liver phosphoglycerides. Neither mitochondrial nor microsomal acyl-CoA:glycerol 3-phosphate acyltransferase (GPAT) activity was altered, although insulin treatment stimulated mitochondrial GPAT activity. However, microsomal acyl-CoA:1-acylglycerol 3-phosphate acyltransferase (1-acyl-GPAT) activity increased (24-33 per cent, p less than 0.01) in the diabetic animals using 3 different acyl-CoA donors: palmitoyl-CoA, oleoyl-CoA and linoleoyl-CoA. SZ-induced diabetes also increased acyl-CoA;1-acylglycerol 3-phosphorylcholine acyltransferase (GPCAT) activity (38-45 per cent, p less than 0.01) with 3 different acyl-CoA donors: oleoyl-CoA, linoleoyl-CoA and arachidonoyl-CoA. 1-acyl-GPAT and GPCAT activity returned to normal with insulin treatment. In contrast to the increased activity of the microsomal fatty acyl-transferases 1-acyl-GPAT and GPCAT, SZ-induced diabetes decreased mitochondrial phospholipase A2 activity and lysophospholipase activity (49-70 per cent, p less than 0.01). Insulin treatment of the diabetic rats corrected the decreased lysophospholipase and stimulated phospholipase A2 activity 35 per cent higher than controls. Since microsomal 1-acyl-GPAT and GPCAT are known to have higher activity toward unsaturated fatty acyl-CoA donors, the increased GPCAT activity coupled with the decreased lysophospholipase activity and the increased 1-acyl-GPAT activity in diabetes would tend to increase the formation of newly synthesized phospholipids containing unsaturated fatty acids. This mechanism plus the decreased fatty acid desaturase (4) may be the factors which alter the fatty acid composition of phosphoglycerides in diabetic rat liver microsomes.
 ...
PMID:Effects of streptozotocin-induced diabetes on phosphoglyceride metabolism of the rat liver. 639 59

Enhancement of arachidonic acid metabolism results in increased insulin secretion. To determine which pathways of arachidonic acid metabolism were involved in this stimulation, we studied the effects of various inhibitors of arachidonate metabolism on arginine-induced insulin and glucagon secretion in the isolated, perfused rat pancreas. The release of PGE2 from the pancreas was monitored to document the efficacy of the inhibitory drugs. p-Bromophenacyl bromide, a phospholipase A2 inhibitor, diminished PGE2 release and significantly inhibited both the early and late phases of insulin and glucagon release in response to arginine. Flurbiprofen, a specific cyclooxygenase inhibitor, decreased the early phase of insulin release and inhibited both phases of arginine-stimulated glucagon secretion; these decreases were concurrent with a large inhibition of PGE2 release. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, at a dose of 10(-5) M did not affect PGE2 release, inhibited the early phase of insulin release, and did not modify glucagon secretion. The combination of flurbiprofen and nordihydroguaiaretic acid, although the most potent in inhibiting PGE2, lowered only the early phase of insulin and had no effect on glucagon secretion. We conclude that: (1) endogenous cyclooxygenase-derived metabolites of arachidonic acid promote insulin and glucagon release, (2) endogenous lipoxygenase products preferentially stimulate insulin release, and (3) phospholipase A2 activity has an intrinsic modulatory effect on insulin and glucagon secretion.
Diabetes 1984 Oct
PMID:Possible role of endogenous arachidonic acid metabolites in stimulated release of insulin and glucagon from the isolated, perfused rat pancreas. 643 60

Phospholipase A2 groups I (pancreatic) and II (synovial) could be a link between local and systemic changes in pregnancy, reflected in catalytic activity. We studied whether normal pregnancy, preeclampsia, preterm labor and four other diseases have processes involving serum phospholipase A2s. Pancreatic and synovial-type phospholipase A2 were measured in the serum of 59 normal pregnant women and 89 patients with pathological pregnancy by newly developed time-resolved fluoroimmunoassays, and the catalytic activity by a radiochemical method using micellar phosphatidylcholine as substrate. During pregnancy weeks 6-14, synovial-type phospholipase A2 and catalytic activity were elevated 2- to 4-fold, but at 37 weeks values were normal. Pregnancy-induced hypertensive diseases increased by 4- to 10-fold the concentration of synovial-type phospholipase A2, reflected in catalytic activity. In 8 out of 14 cases, the enzyme was increased if the fetus was to be delivered prematurely. The enzymes studied remained within the reference interval in cases of hepatogestosis, fetal asphyxia, diabetes and twin pregnancy. Newly developed specific immunoassays for measuring different types of phospholipase A2 in serum can provide insights for clinical follow-up.
 ...
PMID:Group I and group II phospholipase A2 in serum during normal and pathological pregnancy. 822 55

Diabetes mellitus alters the cellular production of eicosanoids in a number of tissues, including the kidney, and these agents have in turn been implicated in the pathogenesis of diabetic nephropathy. As delineated in the streptozotocin diabetic rat (SDR) model, a preferential enhancement of glomerular synthesis of the vasodilatory prostaglandins (PGs) PGE2 and PGI2 with concurrent smaller increases in thromboxane (TX)A2 occurs within 1 week after induction of diabetes. This early alteration in glomerular synthesis of eicosanoids in the SDR has been linked to glucose-induced activation of the glomerular protein kinase C signalling system that enhances phospholipase A2 activity and, therefore, release of membrane-bound arachidonic acid for oxygenation. The preferential increase in glomerular production of vasodilatory PGs may contribute to the glomerular hyperfiltration that is characteristic of early diabetes. After more prolonged (months) diabetes in the SDR, glomerular generation and urinary excretion of thromboxane (TX) are preferentially enhanced. Studies with selective inhibitors of TX synthesis in the SDR have implicated this eicosanoid in the pathogenesis of both albuminuria and glomerular structural changes (basement membrane thickening and mesangial matrix expansion). Direct stimulation of matrix protein production has been demonstrated in cultured mesangial cells in response to both TX and high ambient concentrations of glucose. The actions of TX and glucose on mesangial cell matrix production appear to be interactive, with each signalled through distinct pathways of protein kinase C activation.
 ...
PMID:Eicosanoids in the pathogenesis of the functional and structural alterations of the kidney in diabetes. 823 21

The changes in contents of pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase in rats with streptozotocin (STZ)-induced diabetes have been studied. The contents of pancreatic carboxyl ester lipase and phospholipase A2 decreased by 40% and 45%, respectively, 5 days after injection of STZ, whereas pancreatic lipase steadily increased to 100% over control. The content of lingual lipase decreased sharply by more than 90% 2 days after STZ injection, followed by a tendency to recover slightly. Insulin treatment at a dose abolishing the urine glucose in diabetic rats for 3 days restored the contents of pancreatic lipase, carboxyl ester lipase, and lingual lipase but not pancreatic phospholipase A2. The results indicate that lack of insulin action induces an anticoordinate change in gastrointestinal lipolytic enzymes, with decreases in pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase contents and an increase in pancreatic lipase content.
 ...
PMID:Decrease in contents of pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase in rats with streptozotocin-induced diabetes. 844 51

1. The effect of experimental diabetes mellitus (DM; hyperglycaemic, non-ketototic; 2 months duration) in the rat on receptor-linked prostacyclin (PGI2) synthesis (measured as 6-oxo-PGF1 alpha by radioimmunoassay) was studied in the aorta and urinary bladder using adrenaline, angiotensin II (AII) and acetylcholine (ACh). Signal transduction systems were studied via stimulation of PGI2 synthesis with phorbol ester dibutyrate (PDBU; a protein kinase C activator [PKC]), Ca2+ ionophore A23187 (A23187) and thapsigargin (both elevate intracellular Ca2+, activating phospholipase A2 [PLA2]) and arachidonate (AA; substrate for PGI2 synthesis). 2. In response to adrenaline, AII and phorbol ester, aortic PGI2 release was markedly reduced (all > 75%) in diabetic rats compared to controls. EC50s of the dose-response curves for adrenaline, AII and PDBU were also markedly increased in aortae from DM rats compared to controls. Although there was decreased output of PGI2 in response to A23187 by aortae from diabetic rats compared to controls, there was no difference in the EC50s (mean +/- s.e. mean: diabetic, 2.7 +/- 0.2 x 10(-6) M; controls 2 +/- 0.18 x 10(-6) M). There were no differences in PGI2 release (or in the EC50s) in response to thapsigargin or AA between aortae from diabetic and control rats. 3. In the urinary bladder, there was a marked increase in PGI2 output in response to ACh and a marked decrease in EC50s for the ACh-PGI2 dose-response curves in diabetic rats (EC50 = 5.8 +/- 0.32 x 10(-7) M) compared to controls (EC50 = 2.2 +/- 0.15 x 10(-6) M). Although there was an increase in PGI2 output in the urinary bladders from diabetic rats in response to A23187, there were no differences in the EC50s (control, 1.8 +/- 0.2 x 10-6 M; diabetic, 1.1 +/- 0.15 X 10-6 M). In the urinary bladders, there were no differences in PGI2 output (or the EC50s) in response to PDBU, thapsigargin or AA between diabetic or control rats.4. These data indicate that: (i) reduced PGI2 synthesis coupled to adrenoceptors and AII receptors in the aortae of diabetic rats may be due to diminished PKC activity and not to changes in receptor density and/or affinity, Ca2+ stores, PLA2, cyclo-oxygenase or PGI2 synthase; (ii) the diametrically opposite effect of DM on ACh-stimulated PGI2 synthesis is not due to an increase in PKC activity, but possibly to an increase in muscarine receptor number and/or affinity; (iii) changes in receptor-linked PGI2 synthesis are not ubiquitous in experimental DM and may be organ-specific.
 ...
PMID:Differential changes of adrenoceptor- and muscarinic receptor-linked prostacyclin synthesis by the aorta and urinary bladder of the diabetic rat. 848 22

The endothelial response to kinin stimulation is the result of a series of complex intracellular reactions involving changes in the intracellular concentration of free calcium ([Ca2+]i) and intracellular pH, enhanced phosphorylation of several proteins via the activation of at least four distinct families of protein kinases, and activation of membrane ion transport systems. Some of the more recent developments in this field suggest that endothelial tyrosine kinases and tyrosine phosphatases as well as serine/threonine phosphatases are also activated in response to bradykinin. In addition, the finding that the mitogen-activated protein kinase (MAP kinase) pathway was tyrosine phosphorylated, and presumably activated, in endothelial cells after an increase in [Ca2+]i has wideranging implications for these cells. Indeed, MAP kinase recognizes many different substrates in the cell, including growth factor receptors, microtubule-associated proteins, specific serine-threonine protein kinases, phospholipase A2, and transcription factors. Further recent studies of interest have underscored the role of endothelium-derived hyperpolarizing factor in addition to nitric oxide and prostacyclin in the coronary vasculature. Indeed, this mediator, which seems to be an endothelium-derived, cytochrome P450-derived metabolite of arachidonic acid, would now appear to represent a substantial constitutive component of the vasodilator response to bradykinin.
Diabetes 1996 Jan
PMID:Molecular responses of endothelial tissue to kinins. 852 5


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