Cerebral vascular dysfunction in TallyHo mice: a new model of Type II diabetes

2007 ◽  
Vol 292 (3) ◽  
pp. H1579-H1583 ◽  
Author(s):  
Sean P. Didion ◽  
Cynthia M. Lynch ◽  
Frank M. Faraci
Keyword(s):  
Vascular Function ◽  
Type Ii Diabetes ◽  
Carotid Arteries ◽  
Genetic Model ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Type Ii ◽  
Cranial Window ◽  
Cerebral Arterioles

The purpose of this study was to characterize vascular responses and to examine mechanisms of vascular dysfunction in TallyHo mice, a new polygenic model of Type II diabetes. Responses of cerebral arterioles and carotid arteries were examined in vivo by using a cranial window and in vitro by using tissue baths, respectively. Dilatation of cerebral arterioles (baseline diameter = 33 ± 1 μm) in response to acetylcholine, but not to nitroprusside, was markedly reduced ( P < 0.05) in TallyHo mice. Responses of cerebral arterioles to acetylcholine in TallyHo mice were restored to normal with polyethylene glycol-superoxide dismutase (100 U/ml; a superoxide scavenger). Responses to acetylcholine were also greatly impaired ( P < 0.05) in the carotid arteries from TallyHo mice. Phenylephrine- and serotonin-, but not to KCl- or U46619-, induced contraction was increased two- to fourfold ( P < 0.05) in carotid arteries of TallyHo mice. Responses to phenylephrine and serotonin were reduced to similar levels in the presence of Y-27632 (an inhibitor of Rho kinase; 3 μmol/l). These findings provide the first evidence that vascular dysfunction is present in TallyHo mice and that oxidative stress and enhanced activity of Rho kinase may contribute to altered vascular function in this genetic model of Type II diabetes.

scholarly journals Impaired Endothelium-Dependent Responses and Enhanced Influence of Rho-Kinase in Cerebral Arterioles in Type II Diabetes

Stroke ◽  
2005 ◽  
Vol 36 (2) ◽  
pp. 342-347 ◽  
Author(s):  
Sean P. Didion ◽  
Cynthia M. Lynch ◽  
Gary L. Baumbach ◽  
Frank M. Faraci
Keyword(s):  
Type Ii Diabetes ◽  
Rho Kinase ◽  
Type Ii ◽  
Cerebral Arterioles

Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen

2002 ◽  
Vol 283 (4) ◽  
pp. H1569-H1576 ◽  
Author(s):  
Sean P. Didion ◽  
Michael J. Ryan ◽  
Gary L. Baumbach ◽  
Curt D. Sigmund ◽  
Frank M. Faraci
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Genetic Model ◽  
Vascular Dysfunction ◽  
Enhanced Chemiluminescence ◽  
Human Renin ◽  
Endothelium Dependent Relaxation ◽  
Superoxide Scavenger

This study examined vascular function and the role of superoxide in mice that chronically express human renin (R+) and human angiotensinogen (A+). Responses of aortas from R+/A+ mice and from their normotensive littermates (RA− mice) were examined in vitro. Endothelium-dependent relaxation to acetylcholine was impaired in vessels from R+/A+ mice (e.g., maximal relaxation to 100 μM acetylcholine was 45 ± 5% and 65 ± 3% in R+/A+ and RA− mice, respectively; P < 0.05). Relaxation was also impaired to the endothelium-independent dilators authentic nitric oxide and nitroprusside in vessels from R+/A+ mice. Maximal vasorelaxation to the endothelium-independent, non-nitric oxide dilator papaverine was similar in R+/A+ and RA− mice. Incubation of vessels from R+/A+ mice with Tiron (1 mM), a superoxide scavenger, improved relaxation to acetylcholine, nitric oxide, and nitroprusside. In contrast, incubation with diethyldithiocarbamate (1 mM), an inhibitor of copper-containing SODs, reduced acetylcholine- and nitroprusside-induced relaxation in vessels from both R+/A+ and RA− mice. Basal superoxide levels, measured with lucigenin-enhanced chemiluminescence (5 μM lucigenin) and hydroethidine-based fluorescent confocal microscopy, were higher in vessels from R+/A+ mice and were Tiron and polyethylene glycol-SOD sensitive. These results suggest that increased superoxide contributes to impaired nitric oxide-mediated relaxation in this genetic model of chronic angiotensin II-dependent hypertension.

Reversible impairment of glucose-induced insulin secretion in SHR/N-cp rats. Genetic model of type II diabetes

Diabetes ◽  
1988 ◽  
Vol 37 (4) ◽  
pp. 398-404 ◽  
Author(s):  
N. R. Voyles ◽  
A. M. Powell ◽  
K. I. Timmers ◽  
S. D. Wilkins ◽  
S. J. Bhathena ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Type Ii Diabetes ◽  
Genetic Model ◽  
Type Ii

In vitro and in vivo sustained release of exenatide from vesicular phospholipid gels for type II diabetes

2015 ◽  
Vol 42 (7) ◽  
pp. 1042-1049 ◽  
Author(s):  
Yu Zhang ◽  
Ying Zhong ◽  
Mei Hu ◽  
Nanxi Xiang ◽  
Yao Fu ◽  
...  
Keyword(s):  
Sustained Release ◽  
Type Ii Diabetes ◽  
Type Ii

Formulation and Evaluation of Sustained Release Bilayer Matrix Tablet of Glimepiride and Metformin Hydrochloride

2021 ◽  
pp. 273-279
Author(s):  
Mayuri B. Patil ◽  
Avish D. Maru ◽  
Jayshree S. Bhadane
Keyword(s):  
Sustained Release ◽  
Type Ii Diabetes ◽  
In Vitro Release ◽  
Angle Of Repose ◽  
Metformin Hydrochloride ◽  
Wet Granulation ◽  
Matrix Tablet ◽  
Type Ii ◽  
Weight Variation

The aim of the present study was to design and evaluate bilayer tablets of metformin hydrochloride as sustained release form for the treatment of Type-II diabetes mellitus. The basic aim of any Bi-layer tablet formulation is to separate physically or chemically incompatible ingredients and to produce repeat action or prolonged action of tablet. They are many drugs for treating type-II diabetes. Sulphonyl urea and biguanides are used commonly by a wide section of patients. Melt granulation process was used for the formulation of sustained comprising metformin layer and wet granulation of immediate comprising layer of glimepiride. The precompression studies like bulk density, tapped density, angle of repose, compressible index and post formulation studies includes weight variation, hardness, thickness, friability and dissolution study. The in-vitro release profile of Glimepiride was dissolved within 45 min, and Metformin Hydrochloride was able to release more than 12 hrs. They all the formulation was optimized formula due to its higher rate of dissolution and collate all other parameters with the official specifications.

scholarly journals Potent Natural Inhibitors of Alpha-Glucosidase and Alpha-Amylase against Hyperglycemia in Vitro and in Vivo

2017 ◽  
Author(s):  
Jirawat Riyaphan ◽  
Chien-Hung Jhong ◽  
May-Jwan Tsai ◽  
Der-Nan Lee ◽  
Max K. Leong ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Herbal Medicines ◽  
Alpha Amylase ◽  
Type Ii ◽  
Reference Drug ◽  
Significant Difference ◽  
Natural Inhibitors ◽  
Alpha Glucosidase

The inhibition of alpha-glucosidase and alpha-amylase is one of clinic strategies for remedy the type II diabetes. Herbal medicines are reported to alleviate hyperglycemia. However, the constituents from those sources whether are targeted to the alpha-glucosidase and alpha-amylase still unexplored. This study attempted to select the compounds for efficacy of hypoglycemia via cellular and mouse levels. The results illustrated that the cytotoxicity in all tested compounds at various concentrations except the concentration of 16-hydroxy-cleroda-3,13-dine-16,15-olide (HCD) at 30 &micro;M were not significant difference (p &gt; 0.05) when compared with the untreated control. Acarbose (reference drug), Antroquinonol, Catechin, Quercetin, Actinodaphnine, Curcumin, HCD, Docosanol, Tetracosanol, Berberine, and Rutin could effectively inhibit the alpha-glucosidase activity of Caco-2 cells when compared with the control (maltose). The compounds (Curcumin, HCD, Tetracosanol, Antroquinonol, Berberine, Catechin, Actinodaphnine, and Rutin) could reduce blood sugar level at 30 min in tested mice. The effects of tested compounds on area under curve (AUC) were significant (p &lt; 0.05) among Acarbose, Tetracosanol, Antroquinonol, Catechin, Actinodaphnine, and Rutin along with Berberine and Quercetin. In in vitro (alpha-glucosidase) with in vivo (alpha-amylase) experiments suggest that bioactive compounds can be a potential inhibitor candidate of alpha-glucosidase and alpha-amylase for the alleviation of type II diabetes.

Uncontrolled Hypertension, Uncompensated Type II Diabetes, and Smoking Have Different Patterns of Vascular Dysfunction

CHEST Journal ◽  
2004 ◽  
Vol 125 (3) ◽  
pp. 823-830 ◽  
Author(s):  
Juan Carlos Yugar-Toledo ◽  
Jose Eduardo Tanus-Santos ◽  
Maricene Sabha ◽  
Márcio Gonçalves Sousa ◽  
Máira Cittadino ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Vascular Dysfunction ◽  
Uncontrolled Hypertension ◽  
Type Ii

scholarly journals Glutamine-dependent inhibition of pial arteriolar dilation to acetylcholine with and without hyperammonemia in the rat

2005 ◽  
Vol 288 (6) ◽  
pp. R1612-R1619 ◽  
Author(s):  
Tetsu Kawaguchi ◽  
Saul W. Brusilow ◽  
Richard J. Traystman ◽  
Raymond C. Koehler
Keyword(s):  
Intravenous Infusion ◽  
Ammonium Acetate ◽  
Ammonia Concentration ◽  
Inhibitory Effect ◽  
Glutamine Concentration ◽  
Cranial Window ◽  
Cerebral Arterioles ◽  
Cerebral Glutamine

Glutamine has been shown to influence endothelial-dependent relaxation and nitric oxide production in vitro, possibly by limiting arginine availability, but its effects in vivo have not been well studied. Hyperammonemia is a pathophysiological condition in which glutamine is elevated and contributes to depressed CO2 reactivity of cerebral arterioles. We tested the hypothesis that acute hyperammonemia decreases pial arteriolar dilation to acetylcholine in vivo and that this decrease could be prevented by inhibiting glutamine synthetase with l-methionine- S-sulfoximine (MSO) or by intravenous infusion of l-arginine. Pial arteriolar diameter responses to topical superfusion of acetylcholine were measured in anesthetized rats before and at 6 h of infusion of either sodium or ammonium acetate. Ammonium acetate infusion increased plasma ammonia concentration from ∼30 to ∼600 μM and increased cerebral glutamine concentration fourfold. Arteriolar dilation to acetylcholine was intact after infusion of sodium acetate in groups pretreated with vehicle or with MSO plus methionine, which was coadministered to prevent MSO-induced seizures. In contrast, dilation in response to acetylcholine was completely blocked in hyperammonemic groups pretreated with vehicle or methionine alone. However, MSO plus methionine administration before hyperammonemia, which maintained cerebral glutamine concentration at control values, preserved acetylcholine dilation. Intravenous infusion of l-arginine during the last 2 h of the ammonium acetate infusion partially restored dilation to acetylcholine without reducing cerebral glutamine accumulation. Superfusion of 1 or 2 mM l-glutamine through the cranial window for 1 h in the absence of hyperammonemia attenuated acetylcholine dilation but had no effect on endothelial-independent dilation to nitroprusside. We conclude that 1) hyperammonemia reduces acetylcholine-evoked dilation in cerebral arterioles, 2) this reduction depends on increased glutamine rather than ammonium ions, and 3) increasing arginine partially overcomes the inhibitory effect of glutamine.

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