Exaggerated coronary reactivity to endothelin-1 in diabetes: reversal with bosentan

2002 ◽  
Vol 80 (10) ◽  
pp. 980-986 ◽  
Author(s):  
Subodh Verma ◽  
Emi Arikawa ◽  
Sammy Lee ◽  
Aaron S Dumont ◽  
Linfu Yao ◽  
...  
Keyword(s):  
Heart Function ◽  
Coronary Perfusion Pressure ◽  
Diabetic Rats ◽  
Diabetic Heart ◽  
Coronary Perfusion ◽  
Receptor Blockade ◽  
Endothelin Receptor ◽  
Endothelin 1 ◽  
Streptozotocin Induced Diabetes ◽  
And Control

We previously demonstrated that chronic endothelin receptor blockade (with bosentan) improved functional cardiac performance in streptozotocin-diabetic rats, suggesting a novel role of endothelin-1 (ET-1) in modulating diabetic heart dysfunction. To gain insight into the mechanism(s) underlying this effect, we examined the coronary vascular responses to ET-1 in hearts from diabetic and control rats treated with or without bosentan. Rats were divided into control, control-treated, diabetic, and diabetic-treated groups. The control-treated and diabetic-treated groups received bosentan (100 mg·kg–1·d–1) for 8 weeks. Following treatment, hearts were isolated and perfused, and coronary reactivity to ET-1 was assessed by measuring the changes in coronary perfusion pressure in response to ET-1 (50 and 100 pM). Additionally, maximal coronary blood flow (assessed with 10–5 M adenosine) was measured in isolated perfused hearts. The key observation is that coronary reactivity to ET-1 was significantly higher in the diabetic than the control rats. This effect was normalized in diabetic rats chronically receiving bosentan. Maximal coronary vasodilation did not differ between the four groups. In conclusion, the reactivity of ET-1 is altered in the isolated perfused coronary vascular bed from diabetic rats, and chronic ET receptor blockade restores this reactivity to control values. These observations provide a possible mechanism for the improvement in diabetic heart function observed after chronic bosentan treatment.Key words: endothelin-1, streptozotocin-induced diabetes, bosentan, endothelin receptor antagonist, coronary artery.

Endothelin-1 Receptor Blockade Prevented the Electrophysiological Dysfunction in Cardiac Myocytes of Streptozotocin-Induced Diabetic Rats

Endocrine ◽  
2006 ◽  
Vol 30 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Yanfeng Ding ◽  
Ruijiao Zou ◽  
Robert L. Judd ◽  
Juming Zhong
Keyword(s):  
Cardiac Myocytes ◽  
Diabetic Rats ◽  
Receptor Blockade ◽  
Endothelin 1

Effect of endothelin-1 and endothelin receptor blockade on the release of microparticles

2016 ◽  
Vol 46 (8) ◽  
pp. 707-713 ◽  
Author(s):  
Christian Jung ◽  
Michael Lichtenauer ◽  
Bernhard Wernly ◽  
Marcus Franz ◽  
Bjoern Goebel ◽  
...  
Keyword(s):  
Receptor Blockade ◽  
Endothelin Receptor ◽  
Endothelin 1

Progressive defect in biliary GSH secretion in streptozotocin-induced diabetic rats

1997 ◽  
Vol 272 (2) ◽  
pp. G374-G382 ◽  
Author(s):  
S. C. Lu ◽  
J. Kuhlenkamp ◽  
H. Wu ◽  
W. M. Sun ◽  
L. Stone ◽  
...  
Keyword(s):  
Reduced Glutathione ◽  
Diabetic Rats ◽  
High Dose ◽  
Gamma Glutamyl Transpeptidase ◽  
Irreversible Inhibitor ◽  
Kinase C ◽  
Before And After ◽  
Streptozotocin Induced Diabetes ◽  
And Control ◽  
Glutamyl Transpeptidase

This study examined the effect of streptozotocin-induced diabetes on biliary reduced glutathione (GSH) efflux. Biliary GSH efflux was measured before and after acivicin, an irreversible inhibitor of gamma-glutamyl transpeptidase (GGT). One week after streptozotocin treatment, liver GGT activity doubled in diabetic rats but was inhibited by approximately 90% after acivicin to levels comparable to controls. Despite maximal GGT inhibition, biliary GSH efflux in untreated diabetic rats decreased progressively to approximately 10% of control levels by week 4 and was partially restored by insulin. The mechanism for the decrease in biliary GSH efflux was not increased paracellular permeability. GSH transport kinetics, ATP-stimulated taurocholate, and oxidized glutathione (GSSG) transport in canalicular liver plasma membrane prepared from diabetic and control rats were similar. Inhibition of protein kinase C (PKC) with high-dose H-7 increased biliary GSH efflux in diabetic animals to near control basal levels. In conclusion, streptozotocin-induced diabetic rats exhibit a progressive impairment in biliary GSH transport. One of the responsible mechanisms is heightened PKC tone in diabetic animals.

scholarly journals Activity, distribution and regulation of phosphofructokinase in salivary gland of rats with streptozotocin-induced diabetes

2006 ◽  
Vol 20 (2) ◽  
pp. 108-113 ◽  
Author(s):  
José Nicolau ◽  
Douglas Nesadal Souza ◽  
Fernando Neves Nogueira
Keyword(s):  
Parotid Gland ◽  
Salivary Glands ◽  
Specific Activity ◽  
Active Form ◽  
Diabetic Rats ◽  
Phosphate Content ◽  
Soluble Enzyme ◽  
Parotid Glands ◽  
Streptozotocin Induced Diabetes ◽  
And Control

Although the influence of diabetes on salivary glands is well studied, it still presents conflicting results. In this work, the regulation of the phosphofructokinase-1 enzyme (PFK-1) was studied utilizing the salivary glands of rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/Kg of body weight) in rats (180-200 g). The animals were killed 30 days after the induction of diabetes and the submandibular and parotid salivary glands were used. Hyperglycemia was evaluated by blood sugar determination. The distribution of PFK-1 between the soluble and cytoskeleton fractions, the phosphate content of PFK-1, the content of fructose-2,6-bisphosphate and the activity of the PFK-2 enzyme were determined. The calculated relative glandular weight showed a higher value for the parotid gland in comparison with the control, but not for the submandibular gland. The activity of PFK-1 expressed per gland showed no variation between diabetic and control animals. However, considering the specific activity, the soluble enzyme presented a value 50% higher than that of the control and the cytoskeleton bound form increased by 84% compared to the control. For the parotid gland, no difference in the specific activity between diabetic and control animals was observed. On the other hand, the activity per gland of the soluble enzyme increased in the diabetic animals. The phosphate content of PFK-1 increased in the submandibular and parotid glands of diabetic rats. Both the content of fructose-2,6-bisphosphate and the active form of PFK-2 were reduced in the diabetic glands. In conclusion, the increase in the activity of PFK-1 observed in the salivary glands of rats with streptozotocin-induced diabetes does not seem to be due to its modulator fructose-2,6-bisphosphate.

Exogenous substrate utilization by isolated myocytes from chronically diabetic rats

1983 ◽  
Vol 245 (1) ◽  
pp. C46-C51 ◽  
Author(s):  
V. Chen ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Lactate Oxidation ◽  
Palmitate Oxidation ◽  
Exogenous Substrate ◽  
Streptozotocin Induced Diabetes ◽  
And Control ◽  
Effect Of Glucose ◽  
Substrate Concentrations

The effect of chronic streptozotocin-induced diabetes on the utilization of exogenous substrates by freshly isolated, Ca2+-tolerant nonbeating myocytes was investigated. The rates of glucose (5 or 25 mM) and lactate (1 mM) oxidation were significantly reduced in myocytes of diabetic rats, whereas palmitate (0.4 or 1 mM) oxidation was similar to the controls. Glucose oxidation in diabetic (but not in control) and palmitate oxidation in control (but not in diabetic) myocytes were increased by raising the respective substrate concentrations in the medium to levels found in vivo in diabetic rats. Inhibition of glucose and lactate oxidation in the presence of competing substrates were generally similar between control and diabetic myocytes. However, the inhibitory effect of glucose on lactate oxidation was greater in control cells. The rate of palmitate oxidation was diminished by glucose in the controls, but this was not observed in the diabetic myocytes. Oxygen consumption by the myocytes of diabetic rats was below that of control cells when lactate or palmitate was present in the medium. ATP and phosphocreatine contents were similar in the myocytes of diabetic and control rats. All the observed changes in myocytes prepared from diabetic rats were reversed by in vivo insulin treatment.

scholarly journals Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Mateusz Maciejczyk ◽  
Agnieszka Kossakowska ◽  
Julita Szulimowska ◽  
Anna Klimiuk ◽  
Małgorzata Knaś ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Inverse Correlation ◽  
Salivary Flow ◽  
Diabetic Rats ◽  
Secretory Function ◽  
Submandibular Glands ◽  
Streptozotocin Induced Diabetes ◽  
And Control ◽  
The Relationship

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands—nonstimulated and stimulated salivary flow,α-amylase, total protein—and salivary exoglycosidase activities—N-acetyl-β-hexosaminidase (HEX, HEX A, and HEX B),β-glucuronidase,α-fucosidase,β-galactosidase, andα-mannosidase—was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B,α-amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

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