scholarly journals Platelet Survival and Platelet Serotonin Release in vivo in Various Animal Models

1977 ◽  
Author(s):  
D.I. Cargill ◽  
R.J. Ryan

Decreased platelet survival is a clinically accepted indicator of increased platelet consumption, and in some cases may reveal “hyperthrombotic” states. Decreased platelet survival has also been demonstrated in the homocystinuric baboon and the hypercholesterolemic rhesus monkey (Ross and Harker). Treatment with antiplatelet drugs does increase platelet survival in patients as well as in experimental animals.We have found platelet survival to be decreased in both uricemic and hypercholesterolemic guinea pigs.However, platelet survival in the atherosclerotic rabbit and the streptozotocin diabetic rat was normal. When atherosclerotic rabbits or diabetic rats were given platelets labelled with 51Cr and 14C-serotonin, they were found, five days after receiving the platelets, to have higher 51Cr/14C ratios than did their corresponding controls. This suggests a higher serotonin release from circulating platelets in these models.The 51Cr/14C ratio in platelets may be a more sensitive measure of platelet activity in vivo than is platelet survival alone.

1984 ◽  
Vol 247 (4) ◽  
pp. E526-E533
Author(s):  
A. S. Jennings

The effect of diabetes on 3,5,3'-triiodothyronine (T3) production was determined in the isolated perfused rat liver. Induction of diabetes with streptozotocin resulted in decreased serum thyroxine (T4) and T3 levels and a progressive decline in hepatic T3 production over 5 days. The decline in T3 production resulted from decreased conversion of T4 to T3, whereas T4 uptake was unchanged. Insulin administration restored serum T4 and T3, hepatic conversion of T4 to T3, and T3 production to normal levels. When serum T4 levels in diabetic rats were maintained by T4 administration, the conversion of T4 to T3 and T3 production returned to control levels. However, restoration of serum T4 levels in fasted rats failed to correct the decrease in hepatic T4 uptake or T3 production. Glucagon, at supraphysiological concentrations in vitro and in vivo, slightly decreased T4 uptake and T3 production without altering the conversion of T4 to T3. These data suggest that the fall in serum T4 levels observed in diabetic rats is important in mediating the decreased hepatic conversion of T4 to T3 and T3 production.


2005 ◽  
Vol 25 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Siska Mortier ◽  
Norbert H. Lameire ◽  
An S. De Vriese

The development of an adequate animal model for peritoneal research remains an object of concern. In vivo peritoneal dialysis (PD) research is hampered by the large variety of available models that make interpretation of results and comparison of studies very difficult. Species and strain of experimental animals, method of peritoneal access, study duration, measures of solute transport and ultrafiltration, and sampling for histology differ substantially among the various research groups. A collective effort to discuss the shortcomings and merits of the different experimental models may lead to a consensus on a standardized animal model of PD.


1983 ◽  
Vol 245 (6) ◽  
pp. E560-E567 ◽  
Author(s):  
D. R. Bielefeld ◽  
C. S. Pace ◽  
B. R. Boshell

An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.


Author(s):  
Didem Yilmaz-Oral ◽  
Ecem Kaya-Sezginer ◽  
Dilan Askin ◽  
Yesim Hamurtekin ◽  
Serap Gur

Abstract Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Dong-Seon Kim ◽  
Hyun Dong Ji ◽  
Man Hee Rhee ◽  
Yoon-Young Sung ◽  
Won-Kyung Yang ◽  
...  

Ethnopharmacological Relevance.Morus albaL. leaves (MAE) have been used in fork medicine for the treatment of beriberi, edema, diabetes, hypertension, and atherosclerosis. However, underlying mechanism of MAE on cardiovascular protection remains to be elucidated. Therefore, we investigated whether MAE affect platelet aggregation and thrombosis.Materials and Methods. The anti-platelet activity of MAE was studied using rat platelets. The extent of anti-platelet activity of MAE was assayed in collagen-induced platelet aggregation. ATP and serotonin release was carried out. The activation of integrinαIIbβ3and phosphorylation of signaling molecules, including MAPK and Akt, were investigated with cytofluorometer and immunoblotting, respectively. The thrombus formationin vivowas also evaluated in arteriovenous shunt model of rats.Results. HPLC chromatographic analysis revealed that MAE contained rutin and isoquercetin. MAE dose-dependently inhibited collagen-induced platelet aggregation. MAE also attenuated serotonin secretion and thromboxane A2formation. In addition, the extractin vivoactivity showed that MAE at 100, 200, and 400 mg/kg significantly and dose-dependently attenuated thrombus formation in rat arterio-venous shunt model by 52.3% (P<0.001), 28.3% (P<0.01), and 19.1% (P<0.05), respectively.Conclusions. MAE inhibit platelet activation, TXB2 formation, serotonin secretion, aggregation, and thrombus formation. The plant extract could be considered as a candidate to anti-platelet and antithrombotic agent.


1985 ◽  
Vol 249 (3) ◽  
pp. E312-E316 ◽  
Author(s):  
E. Dall'Aglio ◽  
H. Chang ◽  
C. B. Hollenbeck ◽  
C. E. Mondon ◽  
C. Sims ◽  
...  

The effect of streptozotocin-induced diabetes mellitus on maximal insulin-stimulated glucose uptake in the rat was studied in isolated adipocyte, perfused hindlimb, and the intact organism. Basal glucose transport per fat cell was reduced by approximately two-thirds (P less than 0.001), being associated with a similar decrease in glucose oxidation per fat cell (P less than 0.001). There was also a significant decrease (P less than 0.001) in basal glucose uptake by perfused hindlimb of diabetic rats of approximately 40%. Furthermore, maximal insulin-stimulated glucose transport and oxidation were approximately 50% lower (P less than 0.001) in fat cells of diabetic as compared with control rats. In contrast, maximal insulin-stimulated glucose disposal by perfused hindlimbs from diabetic and control rats was similar, and this was also true of the ability of insulin to maximally stimulate glucose uptake in the intact normal and diabetic rat. These findings indicate that variation exists in the manner in which insulin-sensitive tissues respond to experimentally induced insulin deficiency and support the view that total body glucose disposal is primarily related to insulin action on muscle.


2019 ◽  
Vol 14 (2) ◽  
pp. 80-86 ◽  
Author(s):  
Rahmat Khan ◽  
Wasim Ahmad ◽  
Mushtaq Ahmed

Abstract The objective of this research work was to assess the hyperglycemic and hyperlipidemiceffects of Stellaria media in alloxan induced diabetic rats using different experimental models. Standard documented protocols were used to concede the in vitro and in vivo activities. Biochemical markers studies were also done. The results of the study showed strong pancreatic α-amylase and β-glucosidase inhibition in-vitroat varying concentrations of the extract which further validated the in-vivo anti-diabetic action of the plant because of the inhibition of the above enzymes.The administration of various concentrations of the extract showedmomentous decrease in fasting blood level when compared to diabetic control. Similarly, remarkably improved hemoglobin (+20.10%), and decreased HbA1c (−48.44%) was observed when compared to diabetic control rats. The extract also caused reduced serum enzyme (ALT, ALP, bilirubin) levels and produced a succeeding recovery toward their normal values.It can be concluded from these investigations that the in-vitro and in-vivo hypoglycemic and hypolipidemic activity offers the methodicaljustification for the use of S. media in herb based anti-diabetic treatment.


1983 ◽  
Vol 245 (5) ◽  
pp. G628-G634 ◽  
Author(s):  
M. Korc

The effects of manganese on [3H]phenylalanine incorporation into protein were studied in pancreatic acini prepared from normal and streptozotocin-induced diabetic rats. In the absence of added Ca2+ manganese exerted a biphasic effect on [3H]phenylalanine incorporation in both groups of acini. Significant stimulation occurred at 3 X 10(-5) M manganese. At higher concentrations manganese inhibited incorporation. The magnitude of stimulation was similar in all acini, whereas the magnitude of inhibition was greater in acini from normal rats. Addition of Ca2+ to incubation media abolished the stimulatory effect of manganese in normal rat acini and greatly enhanced it in diabetic rat acini, significant stimulation now occurring at 10(-5) M manganese. The magnitude of inhibition was again greater in acini from normal rats. Insulin in vivo partially reversed the diabetes-induced alterations in acinar cell responsiveness to manganese. The present findings suggest that streptozotocin-induced diabetes is associated with postreceptor alterations in the pancreatic acinar cells.


1990 ◽  
Vol 268 (1) ◽  
pp. 111-115 ◽  
Author(s):  
R A J Challiss ◽  
M J Blackledge ◽  
G K Radda

Phase-modulated rotating-frame imaging (p.m.r.f.i.), a localization technique for 31P-n.m.r. spectroscopy, has been applied to obtain information on the heterogeneity of phosphorus-containing metabolites and pH in the skeletal muscle of control and streptozotocin-diabetic rats. Using this method, the metabolic changes in four spatially resolved longitudinal slices (where slice I is superficial and slice IV is deep muscle) through the ankle flexor muscles have been investigated at rest and during steady-state isometric twitch-contraction at 2 Hz. At rest, intracellular pH was lower, and phosphocreatine (PCr)/ATP was higher, throughout the muscle mass in diabetic compared with control animals. The change in PCr/ATP in diabetic muscle correlated with a decrease in the chemically determined ATP concentration. During the muscle stimulation period, the decrease in pH observed in diabetic muscle at rest was maintained, but not exacerbated, by the contractile stimulus. Stimulation of muscle contraction caused more marked changes in PCr/(PCr + Pi), PCr/ATP and Pi/ATP in the diabetic group. These changes were most evident in slice III, which contains the greatest proportion of fast glycolytic-oxidative (type IIa) fibres, in which statistically significant differences were observed for all metabolite ratios. The results presented suggest that some degree of heterogeneity occurs in diabetic skeletal muscle in vivo with respect to the extent of metabolic dysfunction caused by the diabetic insult and that regions of the muscle containing high proportions of type IIa fibres appear to be most severely affected.


Author(s):  
Ke Meng ◽  
Huabo Cai ◽  
Simin Cai ◽  
Yucai Hong ◽  
Xiaoming Zhang

Background: Accumulating evidence suggested that bone marrow mesenchymal stem cells (BMSCs) have therapeutic potential for diabetes and heart diseases. However, the effects of BMSC on reducing myocardial fibrosis need to be optimized. This study aimed to investigate the mechanism of adiponectin (APN) modified BMSCs on myocardial fibrosis in diabetic model in vivo and in vitro.Methods: The high-fat diet combined with streptozotocin (STZ) injection were used to induced diabetic rat model. H9c2 cells were cultured under a high glucose medium as in vitro model. The BMSCs were modified by APN plasmid or APN small interfering RNA (siRNA), then transplanted to the diabetic rats by a single tail-vein injection, or co-cultured with H9c2 cells.Results: We demonstrated that diabetic rats showed typical diabetic symptoms, such as decreased cardiac function, accumulation of pathological lesions and collagen expression. However, these impairments were significantly prevented by the APN modified BMSCs treatment while no effects on APN siRNA modified BMSCs treated diabetic rats. Moreover, we confirmed that APN modified BMSCs could attenuate the expression of TGF-beta1/smad to suppress the myocardial fibrosis in the diabetic rats and high glucose induced H9c2 cells.Conclusion: The present results for the first time showed that APN modified BMSCs exerted protection on cardiac fibrosis via inhibiting TGF-beta1/smad signal pathway in diabetic rats. Our findings suggested that APN modified BMSCs might be a novel and optimal therapy for the diabetic cardiomyopathy in future.


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