Enhanced arterial contractility to noradrenaline in diabetic rats is associated with increased phosphoinositide metabolism

1991 ◽  
Vol 69 (3) ◽  
pp. 355-361 ◽  
Author(s):  
Worku Abebe ◽  
Kathleen M. MacLeod
Keyword(s):  
Phosphatidic Acid ◽  
Contractile Response ◽  
Inositol Phosphates ◽  
Diabetic Rats ◽  
Male Rats ◽  
Phosphoinositide Metabolism ◽  
Adrenoceptor Antagonist ◽  
Streptozotocin Induced Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
Stimulation Of

The purpose of this study was to investigate whether the increased contractile responsiveness of aortae from male rats with 12 – 14 week streptozotocin-induced diabetes to noradrenaline is associated with alterations in phosphoinositide metabolism. The contractile response to noradrenaline (10 μM) in both the presence and absence of extracellular calcium was significantly enhanced in aortae from diabetic rats. No significant differences were found between control and diabetic arteries in the basal incorporation of 32P and [3H]myo-inositol into phosphoinositides, or in the basal accumulation of [32P]phosphatidic acid and [3H]inositol phosphates. However, noradrenaline (10 μM) caused significantly greater breakdown of [32P]phosphatidylinositol 4,5-bisphosphate and formation of [32P]phosphatidic acid and [3H]inositol phosphates in diabetic aortae than in control preparations. The production of [3H]inositol phosphates induced by noradrenaline was selectively reduced by the α1-adrenoceptor antagonist, prazosin, in both control and diabetic tissues. These results indicate that phosphoinositide metabolism in response to noradrenaline via stimulation of α1-adrenoceptors is enhanced in aortae from chronic streptozotocin-diabetic rats. The increase in inositol 1,4,5-trisphosphate and 1,2-diacylglycerol production that presumably results could be responsible, at least in part, for the enhanced contractile response of aortae from diabetic rats to noradrenaline.Key words: diabetes, aortae, phosphoinositide metabolism, noradrenaline, contractile responses.

Cholinergic stimulation of phosphoinositide metabolism in isolated rat glomeruli

1992 ◽  
Vol 262 (2) ◽  
pp. F256-F266 ◽  
Author(s):  
P. Meneton ◽  
M. Bloch-Faure ◽  
G. Guillon ◽  
D. Chabardes ◽  
F. Morel ◽  
...  
Keyword(s):  
Pertussis Toxin ◽  
Maximum Dose ◽  
Inositol Phosphates ◽  
Effective Concentration ◽  
Phosphoinositide Metabolism ◽  
Cholinergic Stimulation ◽  
Cellular Mechanisms ◽  
Isolated Rat ◽  
Cholinergic Effects ◽  
Stimulation Of

Cholinergic effects on kidney function have been observed in some mammals but the intrarenal localization and the cellular mechanisms of these effects are poorly defined to date. The aim of this work was to study the effects of carbachol on phosphoinositide metabolism in freshly isolated rat glomeruli labeled with myo-[3H]inositol. Carbachol rapidly and markedly stimulates phosphoinositide metabolism with a 50% effective concentration of 3 microM. The enormous magnitude of the response is enlightened by the use of 10 mM lithium, which provokes in the presence of the agonist a large accumulation of inositol phosphates and a corresponding depletion of cellular free inositol. The response is inhibited by 85% by pirenzepine, is pertussis toxin insensitive, and shows no desensitization at maximum dose of carbachol up to 40 min of stimulation.

scholarly journals Inhibitory effects of some long-chain unsaturated fatty acids on mitochondrial β-oxidation. Effects of streptozotocin-induced diabetes on mitochondrial β-oxidation of polyunsaturated fatty acids

1985 ◽  
Vol 230 (2) ◽  
pp. 329-337 ◽  
Author(s):  
H Osmundsen ◽  
K Bjørnstad
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Reductase Activity ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Inhibitory Property ◽  
Streptozotocin Induced Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
Coa Reductase

Evidence showing that some unsaturated fatty acids, and in particular docosahexaenoic acid, can be powerful inhibitors of mitochondrial β-oxidation is presented. This inhibitory property is, however, also observed with the cis- and trans-isomers of the C18:1(16) acid. Hence it is probably the position of the double bond(s), and not the degree of unsaturation, which confers the inhibitory property. It is suggested that the inhibitory effect is caused by accumulation of 2,4-di- or 2,4,7-tri-enoyl-CoA esters in the mitochondrial matrix. This has previously been shown to occur with these fatty acids, in particular when the supply of NADPH was limiting 2,4-dienoyl-CoA reductase (EC 1.3.1.-) activity [Hiltunen, Osmundsen & Bremer (1983) Biochim. Biophys. Acta 752, 223-232]. Liver mitochondria from streptozotocin-diabetic rats showed an increased ability to β-oxidize 2,4-dienoyl-CoA-requiring acylcarnitines. Docosahexaenoylcarnitine was also found to be less inhibitory at lower concentrations with incubation under coupled conditions. With uncoupling conditions there was little difference between mitochondria from normal and diabetic rats in these respects. This correlates with a 5-fold stimulation of 2,4-dienoyl-CoA reductase activity found in mitochondria from streptozotocin-diabetic rats.

scholarly journals Glutamine and ketone-body metabolism in the gut of streptozotocin-diabetic rats

1988 ◽  
Vol 249 (2) ◽  
pp. 565-572 ◽  
Author(s):  
M S M Ardawi
Keyword(s):  
Small Intestine ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Glutamine Metabolism ◽  
Gut Mucosa ◽  
Streptozotocin Induced Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
Short And Long Term

1. In short- and long-term diabetic rats there is a marked increase in size of both the small intestine and colon, which was accompanied by marked decreases (P less than 0.001) and increases (P less than 0.001) in the arterial concentrations of glutamine and ketone bodies respectively. 2. Portal-drained viscera blood flow increased by approx. 14-37% when expressed as ml/100 g body wt., but was approximately unchanged when expressed as ml/g of small intestine of diabetic rats. 3. Arteriovenous-difference measurements for ketone bodies across the gut were markedly increased in diabetic rats, and the gut extracted ketone bodies at approx. 7 and 60 nmol/min per g of small intestine in control and 42-day-diabetic rats respectively. 4. Glutamine was extracted by the gut of control rats at a rate of 49 nmol/min per g of small intestine, which was diminished by 45, 76 and 86% in 7-, 21- and 42-day-diabetic rats respectively. 5. Colonocytes isolated from 7- or 42-day-diabetic rats showed increased and decreased rates of ketone-body and glutamine metabolism respectively, whereas enterocytes of the same animals showed no apparent differences in the rates of acetoacetate utilization as compared with control animals. 6. Prolonged diabetes had no effects on the maximal activities of either glutaminase or ketone-body-utilizing enzymes of colonic tissue preparations. 7. It is concluded that, although the epithelial cells of the small intestine and the colon during streptozotocin-induced diabetes exhibit decreased rates of metabolism of glutamine, such decreases were partially compensated for by enhanced ketone-body utilization by the gut mucosa of diabetic rats.

scholarly journals Decreased astrocytic GFAP expression in streptozotocin-induced diabetes after gliotoxic lesion in the rat brainstem

2013 ◽  
Vol 57 (6) ◽  
pp. 431-436 ◽  
Author(s):  
Eduardo Fernandes Bondan ◽  
Maria de Fátima Monteiro Martins ◽  
Flávio Cesar Viani
Keyword(s):  
Saline Solution ◽  
Single Injection ◽  
Diabetic Rats ◽  
Male Rats ◽  
Image Analysis System ◽  
Immunohistochemical Expression ◽  
Gfap Expression ◽  
Streptozotocin Induced Diabetes ◽  
Rat Brainstem ◽  
Analysis System

OBJECTIVE: The aim of this study was to evaluate the effect of diabetic hyperglycemia on astrocyte function, estimated by means of glial fibrillary acidic protein - GFAP - immunohistochemical expression. MATERIALS AND METHODS: Adult male rats received a single intravenous injection of streptozotocin (50 mg/kg) and were submitted 10 days later to a single injection of 10 microlitres 0.1% EB solution or 0.9% saline solution into the cisterna pontis. Ten microliters of 0.1% EB or 0.9% saline solution were also injected in non-diabetic rats. Animals were anesthetized and perfused through the heart 15 and 31 days after EB or saline injection, and brainstem sections were collected for ultrastructural analysis and GFAP immunohistochemical staining. RESULTS: The GFAP brown-stained areas were evaluated by colorimetry using a computerized image analysis system and the results have shown that diabetes hindered the increase of GFAP astrocyte expression in the EB-injected group compared to non-diabetic animals. However, diabetes did not affect GFAP response in the saline-injected group or in control animals. CONCLUSION: Streptozotocin-induced diabetic condition reduced astrocytic GFAP expression following gliotoxic injury.

Protein synthesis in liver and small intestine in protein deprivation and diabetes

1981 ◽  
Vol 241 (3) ◽  
pp. E238-E245 ◽  
Author(s):  
M. A. McNurlan ◽  
P. J. Garlick
Keyword(s):  
Protein Synthesis ◽  
Small Intestine ◽  
Dietary Protein ◽  
Young Male ◽  
Diabetic Rats ◽  
Male Rats ◽  
Jejunal Mucosa ◽  
Protein Deprivation ◽  
Protein Pool ◽  
Streptozotocin Diabetic Rats

Protein synthesis (as a percent of the protein pool synthesized per day) has been measured in liver and small intestine of young male rats from the incorporation of 100 mumol [1–14C]leucine/100 g body wt into protein over 10 min. Dietary protein deprivation for 8 days depressed protein synthesis in liver (30%), jejunal mucosa (20%), and jejunal serosa (25%). In serosa, reduced levels of RNA relative to protein could account for altered synthesis; in liver and mucosa, the amount of protein synthesized per unit RNA was reduced. In liver of streptozotocin-diabetic rats protein synthesis was depressed 45%, whereas it was maintained in jejunal mucosa and serosa. Depressed synthesis in liver was accompanied by both a loss of RNA relative to protein and a reduction in the protein synthesized per RNA.

scholarly journals The action of the protein kinase C inhibitor, staurosporine, on human platelets. Evidence against a regulatory role for protein kinase C in the formation of inositol trisphosphate by thrombin

1988 ◽  
Vol 249 (2) ◽  
pp. 345-350 ◽  
Author(s):  
S P Watson ◽  
J McNally ◽  
L J Shipman ◽  
P P Godfrey
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phosphatidic Acid ◽  
Phorbol Esters ◽  
Inositol Phosphates ◽  
Protein A ◽  
Polymyxin B ◽  
Human Platelets ◽  
Phosphoinositide Metabolism ◽  
Kinase C

The ability of several putative inhibitors of protein kinase C (PKC) to block dioctanoylglycerol (DC8)-induced phosphorylation of a 47 kDa protein (a recognized substrate for PKC) in human platelets was investigated. Staurosporine (1 microM) caused complete inhibition of phosphorylation, whereas the other reagents were either inactive (polymyxin B) or gave only partial inhibition (C-1, H-7, tamoxifen). Staurosporine (1 microM) fully inhibited the phosphorylation of the 47 kDa protein in platelets challenged with thrombin, but also inhibited the phosphorylation of a 20 kDa protein which is a substrate for myosin light-chain kinase. The inhibition of both kinases by staurosporine was associated with the inhibition of thrombin-induced secretion of ATP and 5-hydroxytryptamine and a slowing of the aggregation response; staurosporine, however, had no effect on the formation of phosphatidic acid and inositol phosphates induced by thrombin. Staurosporine also reversed the inhibitory action of phorbol esters on thrombin-induced formation of phosphatidic acid. These data are consistent with a role for these two kinases in secretion and aggregation (although there must be additional control signals, since aggregation was only slowed, not inhibited), but suggest that neither kinase is involved in the regulation of phosphoinositide metabolism. This latter conclusion contradicts previous observations that the activation of PKC by phorbol esters or membrane-permeable diacylglycerols alters the apparent activity of both phospholipase C and inositol trisphosphatase. Possible explanations for this discrepancy are discussed.

scholarly journals Enzymes of myo-inositol and inositol lipid metabolism in rats with streptozotocin-induced diabetes

1979 ◽  
Vol 179 (3) ◽  
pp. 549-553 ◽  
Author(s):  
P H Whiting ◽  
K P Palmano ◽  
J N Hawthorne
Keyword(s):  
Glucuronic Acid ◽  
Single Injection ◽  
Diabetic Rats ◽  
Male Rats ◽  
Inositol 1 ◽  
Phosphatidylinositol Kinase ◽  
Inositol Lipids ◽  
Streptozotocin Induced Diabetes ◽  
Specific Activities ◽  
Phosphatidylinositol 4

Diabetes, with only mild ketosis, was induced in male rats by a single injection of streptozotocin. After 12 weeks the specific activities of enzymes concerned with the metabolism of inositol and of inositol lipids were measured in various tissues. Inositol 1-phosphate synthase (EC 5.5.1.4) was most active in testis and the activity was significantly less in diabetic rats than in controls on a similar diet. Inositol oxygenase (EC 1.13.99.1), which converts myo-inositol into glucuronic acid, was also less active in kidney from diabetic animals. CDP-diacylglycerol-inositol phosphatidyltransferase (EC 2.7.8.11) and phosphatidylinositol 4-phosphate kinase (EC 2.7.1.68) showed decreased specific activities in brain and sciatic nerve of diabetic rats. By contrast the diabetic state did not affect the specific activities of phosphatidylinositol kinase (EC 2.7.1.67) or phosphatidylinositol 4,5-bisphosphate phosphatase (EC 3.1.3.36) in these tissues. The results are discussed in relation to diabetic neuropathy.

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