Platelet Abnormalities in Experimental Diabetes

1979 ◽  
Author(s):  
M. Johnson ◽  
H.E. Harrison ◽  
R. Hawker ◽  
L. Hawker
Keyword(s):  
Platelet Function ◽  
Experimental Diabetes ◽  
Platelet Reactivity ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Thromboxane Synthetase ◽  
Patients With Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
And Control

Many abnormalities of platelet function occur in patients with diabetes mellitus, partioularly those with angiopathy. We have previously demonstrated that prostacyclin (PGI2) is decreased in streptozotocin-diabetic rats, and have now investigated platelet reactivity in these animals. Responsiveness to ADP and arachidonlc acid was increased, and platelet cyclo-oxygenase and thromboxane synthetase activities were significantly elevated (p<0.05) in diabetic animals (5.5±0.7 and 5.9±0.9 arbitrary units/109 platelets) when compared with control animals (J.0±0.4 and 3.9±0.3 arbitrary units/109 platelets). Malondialdehyde synthesis was 1,5 and 0.9 n moles per 108 platelets in diabetic and control rats respectively. Diabetic platelets were also less sensitive to the anti-aggregating effects of PGI2 (IC50: diabetic, 2.3 ng/ml; control, 1.3 ng/ml. Survival of illindium-labelled autologous platelets was significantly reduced, indicating that platelet function is abnormal in vivo, in diabetic animals. Platelet hyper-reactivity, possibly associated with depressed PGI2, could be related to the vascular complications of diabetes.

Abnormal Arachidonic Acid Metabolism In Diabetes: Effect Of Normalisation With Drugs

1981 ◽  
Author(s):  
M Johnson ◽  
A H Reece ◽  
H E Harrison
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Acid Metabolism ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Diabetic Rats ◽  
Arachidonic Acid Metabolism ◽  
Thromboxane Synthetase ◽  
Low Dose Aspirin ◽  
Patients With Diabetes

Patients with diabetes mellitus develop microvascular complications and have an increased susceptibility to both atherosclerosis and arterial thrombosis. We have demonstrated an imbalance in arachidonic acid metabolism in diabetes, vascular prostacyclin (PGI2) being reduced and platelet thromboxane (TxA2) being elevated. Platelet aggregation in response to ADP and arachidonic acid is also increased, and platelet survival is decreased. Treatment of diabetic rats with a specific thromboxane synthetase inhibitor, 1-nonyl-imidazole (50mg/Kg), for 7 days significantly (p<0.05) inhibited platelet aggregation and TxA2 synthesis. Aortic PGI2 production was increased and there was now no difference between treated animals (0.39 ± 0.05ng/mg) and non-diabetic controls (0.4l ± 0.04ng/mg). “Low dose” aspirin (2.5mg/Kg) further decreased PGI2 levels. Chronic treatment of diabetic animals for 3 months with 1-nonyl-imidazole restored both TxA2 and PGI2 production to normal, and significantly reduced the incidence and severity of microvascular lesions. If an imbalance in arachidonic acid metabolism plays a role in the vascular complications of diabetes, then the apparent beneficial effect of some drugs has important implications for therapy.

scholarly journals Adrenoceptor-linked [45Ca2+] uptake in platelets from diabetic rats: a model for human platelets

1994 ◽  
Vol 28 (2) ◽  
pp. 143-147 ◽  
Author(s):  
J. Gill ◽  
C. S. Thompson ◽  
J. Y. Jeremy ◽  
D. P. Mikhailidis
Keyword(s):  
Platelet Function ◽  
Calcium Uptake ◽  
Experimental Diabetes ◽  
Human Platelets ◽  
Diabetic Rats ◽  
Calcium Dynamics ◽  
Beta Adrenoceptors

Adrenoceptor-linked 45calcium uptake was investigated in platelets from diabetic rats (hyperglycaemic, streptozotocin-induced, of 60 days duration). Basal uptake was markedly enhanced in platelets from diabetic rats compared with controls. However, whereas adrenaline-stimulated uptake was unchanged, isoprenaline-stimulated uptake was significantly reduced and noradrenaline-stimulated uptake significantly increased. These latter data indicate that there are differential alterations of adrenoceptor subtypes in diabetes (i.e. an increase in alpha- but decrease in beta-adrenoceptors). These changes in calcium uptake and in adrenoceptor activity may relate to altered platelet function known to occur in experimental diabetes. Furthermore, the similarity of the rat platelet with that of the human (in terms of absolute calcium uptake, responses to agonists and changes in diabetes), renders the rat platelet an appropriate model for studying calcium dynamics and linked adrenoceptors in diabetes.

Parotid Gland Function in Streptozotocin-diabetic Rats

1987 ◽  
Vol 66 (2) ◽  
pp. 425-429 ◽  
Author(s):  
L.C. Anderson
Keyword(s):  
Protein Composition ◽  
Diabetic Rats ◽  
Response Threshold ◽  
Maximal Response ◽  
Parotid Glands ◽  
Threshold Response ◽  
Parotid Acinar Cells ◽  
Streptozotocin Diabetic Rats ◽  
Gland Function

The in vivo response of parotid glands to adrenergic, cholinergic, and peptidergic agonists was studied in control, streptozotocin- (one month's duration), and insulin-treated (three hr) diabetic rats. Neither diabetes nor insulin had an effect on the response to physalaemin. In contrast, physalaemin threshold-dose was lower and maximal response greater in control rats placed on a bulk diet. As previously described, diabetes resulted in nonparallel changes in parotid protein composition, including a reduction in amylase and an increase in peroxidase concentrations (mg/mg protein). In contrast to the results observed with physalaemin, response to methacholine was significantly reduced in diabetic animals, and could be restored to control levels by insulin. Placement of animals on a bulk-diet, however, had no effect on threshold response to methacholine. Finally, response threshold for epinephrine was unaffected by diabetes, insulin, or bulk diet. Thus, insulin appears, directly and specifically, to alter the response of parotid acinar cells to cholinergic stimulation.

Insulin metabolism by liver, muscle, and kidneys from spontaneously diabetic rats

1986 ◽  
Vol 250 (5) ◽  
pp. E530-E537
Author(s):  
R. Rabkin ◽  
G. M. Reaven ◽  
C. E. Mondon
Keyword(s):  
Diabetic Rats ◽  
Insulin Clearance ◽  
Immunoreactive Insulin ◽  
Insulin Metabolism ◽  
Complex Process ◽  
Consistent Manner ◽  
Liver And Kidney ◽  
Spontaneously Diabetic Rats ◽  
And Control

The in vivo metabolism of insulin is a complex process in which liver, kidney, and muscle are major participants. In this study we evaluated the effect of spontaneous hyperglycemic nonketoacidotic diabetes (DH) and ketoacidotic diabetes (DKA) on insulin clearance and degradation by these organs. Livers, hindlimbs, and kidneys from nondiabetic controls and DH and DKA Bio-Breed rats were isolated and perfused with artificial media. Liver clearance of immunoreactive insulin (ml/min) was significantly higher in DH rats, 6.0 +/- 0.2, but significantly lower in DKA rats, 3.4 +/- 0.5, compared with controls, 4.6 +/- 0.2. Acidosis alone induced by ammonium chloride loading, did not impair liver insulin clearance (4.8 +/- 0.4 ml/min). Muscle responded differently to the diabetic state in that insulin clearance was not altered by DH and DKA. Renal (organ) clearance of insulin was significantly depressed in the DKA state when compared with controls (0.52 +/- 0.04 and 0.75 +/- 0.07 ml X min-1 X g-1, respectively). This could largely be explained by a lower glomerular filtration rate. Fractional urinary insulin clearance was increased twofold above control values in DH kidneys and fourfold in DKA kidneys, indicating that tubular luminal absorption of insulin was impaired in both states. By contrast contraluminal uptake (peritubular clearance) did not differ significantly from controls. 125I-insulin degrading activity of the 100,000 g supernate fraction from muscle homogenates was similar in the diabetic and control groups. However in liver and kidney, degrading activity did not correspond to whole organ insulin clearance in a consistent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Sara Rocío Chuguransky ◽  
Ana María Cortizo ◽  
Antonio Desmond McCarthy
Keyword(s):  
Bone Marrow ◽  
Experimental Diabetes ◽  
Bone Microarchitecture ◽  
Bone Matrix ◽  
Diabetic Rats ◽  
Long Bone ◽  
Osteogenic Potential ◽  
Bone Marrow Progenitor

Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs) that impair bone marrow progenitor cell (BMPC) osteogenic potential and decrease bone quality. Here we investigated the in vitro effect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats. We also evaluated the in vivo effect of alendronate (administered orally to rats with insulin-deficient Diabetes) on long-bone microarchitecture and BMPC multilineage potential. In vitro, the osteogenesis (Runx2, alkaline phosphatase, type 1 collagen, and mineralization) and chondrogenesis (glycosaminoglycan production) of BMPC were both decreased by AGEs, while coincubation with alendronate prevented these effects. The adipogenesis of BMPC (PPARγ, intracellular triglycerides, and lipase) was increased by AGEs, and this was prevented by coincubation with alendronate. In vivo, experimental Diabetes (a) decreased femoral trabecular bone area, osteocyte density, and osteoclastic TRAP activity; (b) increased bone marrow adiposity; and (c) deregulated BMPC phenotypic potential (increasing adipogenesis and decreasing osteogenesis and chondrogenesis). Orally administered alendronate prevented all these Diabetes-induced effects on bone. Thus, alendronate could improve bone alterations in diabetic rats by preventing the antiosteogenic, antichondrogenic, and proadipocytic effects of AGEs on BMPC.

scholarly journals The metabolism of l-phenylalanine and l-tyrosine by liver cells isolated from adrenalectomized rats and from streptozotocin-diabetic rats

1985 ◽  
Vol 228 (1) ◽  
pp. 249-255 ◽  
Author(s):  
J C Stanley ◽  
M J Fisher ◽  
C I Pogson
Keyword(s):  
Insulin Treatment ◽  
Maximal Activity ◽  
Liver Cells ◽  
Diabetic Rats ◽  
Steroid Treatment ◽  
Phosphorylation State ◽  
Tyrosine Metabolism ◽  
Streptozotocin Diabetic Rats ◽  
Adrenalectomized Rats

Flux through, and maximal activities of, key enzymes of phenylalanine and tyrosine degradation were measured in liver cells prepared from adrenalectomized rats and from streptozotocin-diabetic rats. Adrenalectomy decreased the phenylalanine hydroxylase flux/activity ratio; this was restored by steroid treatment in vivo. Changes in the phosphorylation state of the hydroxylase may mediate these effects; there was no significant change in the maximal activity of the hydroxylase. Tyrosine metabolism was enhanced by adrenalectomy; this was not related to any change in maximal activity of the aminotransferase. Steroid treatment increased the maximal activity of the aminotransferase. Both acute (3 days) and chronic (10 days) diabetes were associated with increased metabolism of phenylalanine; insulin treatment in vivo did not reverse these changes. Although elevated hydroxylase protein concentration was a major factor, changes in the enzyme phosphorylation state may contribute to differences in phenylalanine degradation in the acute and chronic diabetic states. Tyrosine metabolism, increased by diabetes, was partially restored to normal by insulin treatment in vivo. These changes can, to a large extent, be interpreted in terms of changes in the maximal activity of the aminotransferase.

The effects of diet and duration of diabetes on hypermethioninemia in streptozotocin-diabetic rats

1988 ◽  
Vol 66 (1) ◽  
pp. 95-100 ◽  
Author(s):  
J. R. Dyer ◽  
C. E. Greenwood ◽  
M. I. McBurney
Keyword(s):  
Amino Acid ◽  
Nitrogen Balance ◽  
Diabetic Rats ◽  
Large Neutral Amino Acid ◽  
Duration Of Diabetes ◽  
Amino Acid Availability ◽  
Amino Acid Profiles ◽  
Streptozotocin Diabetic Rats ◽  
The Difference ◽  
And Control

There are conflicting reports concerning the existence of severe hypermethioninemia in rats made diabetic with the pancreotoxin, streptozotocin. To determine whether this discrepancy is due to experimental differences in the severity of diabetes or the diet fed to the animals, streptozotocin-diabetic and control rats were fed either a casein-based semipurified diet or laboratory chow for 2 or 5 weeks. Plasma methionine concentrations were elevated six- to nine-fold after 2 weeks in the casein-fed diabetics compared with both their own controls and the chow-fed diabetics, respectively. Circulating methionine levels had declined sharply by 5 weeks in the casein-fed diabetics but were still more than twice those of the casein-fed control and chow-fed diabetic levels. Since methionine intakes were only 30% greater in the casein-fed diabetics than in the chow-fed diabetics, it is unlikely that this is the sole cause of the large differences in plasma methionine levels. The reason for the difference in circulating Met levels could not be explained on the basis of overall amino acid availability, since growth, nitrogen balance, and plasma large neutral amino acid profiles (excluding Met) were similar within control and diabetic groups fed the two diets.

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