Down-Regulation of Vasopressin VlA Receptor mRNA in Diabetes Mellitus in the Rat

1995 ◽  
Vol 88 (6) ◽  
pp. 671-674 ◽  
Author(s):  
Paddy A. Phillips ◽  
John Risvanis ◽  
Anne-Marie Hutchins ◽  
Louise M. Burrell ◽  
Duncan MacGregor ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Radioligand Binding ◽  
Inositol Phosphates ◽  
Density Ratio ◽  
Northern Blotting ◽  
Diabetic Rats ◽  
Down Regulation ◽  
Receptor Mrna ◽  
V1a Receptor ◽  
Streptozotocin Induced Diabetes

1. To investigate the mechanism of hepatic V1a vasopressin receptor down-regulation in streptozotocin-induced diabetes mellitus in the rat, we measured hepatic V1a receptor mRNA by in situ hybridization histochemistry using oligonucleotide probes to the V1a receptor and Northern blotting. 2. Diabetes mellitus caused hyperglycaemia, hyperosmolality and increased plasma vasopressin concentrations (P < 0.01). Hepatoycte V1a receptor mRNA was reduced by 76% in diabetic rats (P < 0.01) and by 53% in insulin-treated diabetic rats (P < 0.01) versus control rats, in parallel with reduced V1a radioligand binding and vasopressin-stimulated inositol phosphates production. There was a similar decrease in hepatic V1a/18S mRNA density ratio in the diabetic and diabetic + insulin groups (both P < 0.05 versus control). 3. These findings suggest that altered V1a mRNA transcription is responsible for the reduced hepatic V1a receptor density in diabetes mellitus.

Vasopressin V1 and V2 receptors in diabetes mellitus

1994 ◽  
Vol 266 (2) ◽  
pp. E217-E223 ◽  
Author(s):  
D. Trinder ◽  
P. A. Phillips ◽  
J. M. Stephenson ◽  
J. Risvanis ◽  
A. Aminian ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Inositol Phosphate ◽  
Free Water ◽  
Diabetic Rats ◽  
Biological Responses ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes ◽  
V2 Receptor ◽  
Plasma Arginine ◽  
Long Acting

Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may contribute to the polyuria through diminished V2 receptor-mediated free water retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc, daily) partially lowered these values (P < 0.01). There was a reduction in the number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The receptor affinity remained unchanged. In parallel, there was a reduction in maximum AVP-activated total inositol phosphate production in the liver and kidney of the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The density and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic monophosphate production in the diabetic and diabetic+insulin animals were unchanged compared with the sham. These results demonstrate differential regulation of AVP receptors and suggest that downregulation of renal V2 receptors does not contribute to the polyuria of diabetes. In contrast, downregulation of V1 receptors might contribute to diminished V1 receptor-mediated biological responses to AVP seen in diabetes mellitus.

scholarly journals The acute effects of different spironolactone doses on cardiac function in streptozotocin-induced diabetic rats

2017 ◽  
Vol 95 (11) ◽  
pp. 1343-1350
Author(s):  
Aleksandra Vranic ◽  
Stefan Simovic ◽  
Petar Ristic ◽  
Tamara Nikolic ◽  
Isidora Stojic ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systolic Function ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Albino Rats ◽  
Acute Administration ◽  
Rat Hearts ◽  
Patients With Diabetes ◽  
Streptozotocin Induced Diabetes ◽  
Wistar Albino Rats

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μmol/L of spironolactone, diabetic rats treated with 0.1 μmol/L of spironolactone, healthy rats treated with 3 μmol/L of spironolactone, and diabetic rats treated with 3 μmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.

scholarly journals Comparison of the Effects of Glibenclamide on Metabolic Parameters, GLUT1 Expression, and Liver Injury in Rats With Severe and Mild Streptozotocin-Induced Diabetes Mellitus

Medicina ◽  
2012 ◽  
Vol 48 (10) ◽  
pp. 78 ◽  
Author(s):  
Jelizaveta Sokolovska ◽  
Sergejs Isajevs ◽  
Olga Sugoka ◽  
Jelena Sharipova ◽  
Natalia Paramonova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Protein Expression ◽  
Diabetic Rats ◽  
Metabolic Parameters ◽  
Gene And Protein Expression ◽  
Glut1 Expression ◽  
Mild Diabetes ◽  
Streptozotocin Induced Diabetes ◽  
Glut1 Gene

Background and Objective. Glucose transport via GLUT1 protein could be one of additional mechanisms of the antidiabetic action of sulfonylureas. Here, the GLUT1 gene and the protein expression was studied in rats in the course of severe and mild streptozotocin-induced diabetes mellitus and under glibenclamide treatment. Material and Methods. Severe and mild diabetes mellitus was induced using different streptozotocin doses and standard or high fat chow. Rats were treated with glibenclamide (2 mg/kg daily, per os for 6 weeks). The therapeutic effect of glibenclamide was monitored by measuring several metabolic parameters. The GLUT1 mRNA and the protein expression in the kidneys, heart, and liver was studied by means of real-time R T-PCR and immunohistochemistry. Results. The glibenclamide treatment decreased the blood glucose concentration and increased the insulin level in both models of severe and mild diabetes mellitus. Severe diabetes mellitus provoked an increase in both GLUT1 gene and protein expression in the kidneys and the heart, which was nearly normalized by glibenclamide. In the kidneys of mildly diabetic rats, an increase in the GLUT1 gene expression was neither confirmed on the protein level nor influenced by the glibenclamide treatment. In the liver of severely diabetic rats, the heart and the liver of mildly diabetic rats, the GLUT1 gene and the protein expression was changed independently of each other, which might be explained by abortive transcription, and pre- and posttranslational modifications of gene expression. Conclusions. The GLUT1 expression was found to be affected by the glucose and insulin levels and can be modulated by glibenclamide in severely and mildly diabetic rats. Glibenclamide can prevent the liver damage caused by severe hyperglycemia.

Effect of pancreas transplantation on decreased levels of circulating bone γ-carboxyglutamic acid-containing protein and osteopenia in rats with streptozotocin-induced diabetes

1992 ◽  
Vol 127 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Hitoshi Ishida ◽  
Yutaka Seino ◽  
Noritaka Takeshita ◽  
Takeshi Kurose ◽  
Kazuo Tsuji ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Bone Turnover ◽  
Pancreas Transplantation ◽  
Diabetic Rats ◽  
Chronic Complications ◽  
Carboxyglutamic Acid ◽  
Low Bone Turnover ◽  
Streptozotocin Induced Diabetes ◽  
Diabetic Osteopenia

Diabetic osteopenia has been known as one of the chronic complications of diabetes mellitus, and a decrease in bone turnover has been thought to be one of the pathophysiological characteristics of this complication. In order to investigate the effect of long-term insulin therapy on low bone turnover in diabetes, pancreas transplantation was performed on streptozotocin-induced diabetic rats. Plasma levels of bone γ-carboxyglutamic acid-containing protein(osteocalcin) in untreated diabetic rats were 0.9±0.1 (mean±sem) nmol/l, significantly lower than the value of 4.2±0.6 nmol/l in control rats (p<0.01). Pancreas transplantation reversed this decrease to 6.3±1.1 nmol/l, which was not significantly different from the value in control rats. The circulating levels of calcitriol were significantly decreased in the untreated diabetic group (p<0.01), and the decrease was fully reversed by pancreas transplantation. In addition, the decreases in bone length, strength and weight were also improved by the transplantation. This evidence clearly shows that the improvement of metabolic derangements in diabetes by insulin is essential for the prevention of deterioration in diabetic osteopenia. It is possible, therefore, that insulin exerts an indirect beneficial influence through the metabolic amelioration on the decreases in bone turnover and circulating osteocalcin in diabetes mellitus, or has a direct stimulatory effect on the osteoblasts via the insulin receptor since its presence has been shown recently in osteoblastic cells.

Effects of streptozotocin-induced diabetes mellitus on some bone turnover markers in the vertebrae of ovary-intact and ovariectomized adult rats

2006 ◽  
Vol 84 (5) ◽  
pp. 728-736 ◽  
Author(s):  
V. Gopalakrishnan ◽  
J. Arunakaran ◽  
M. M. Aruldhas ◽  
N. Srinivasan
Keyword(s):  
Diabetes Mellitus ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Diabetic Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Adult Rats ◽  
Trap Activity ◽  
Female Wistar Rats ◽  
Streptozotocin Induced Diabetes ◽  
Turnover Markers

Diabetes mellitus and estrogen deficit are known causes of osteopenia in animal models as well as in humans. In the present work, the combined effect of ovariectomy and diabetes was investigated. Diabetes was induced in ovary-intact and ovariectomized female Wistar rats with a single injection (50 mg/kg body weight, i.p.) of streptozotocin. The rats were administered insulin (I) daily or 17-β estradiol (E2) on alternate days for a period of 35 days and sacrificed. Serum calcium (Ca2+), phosphorus (P), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), vertebral ALP, collagen, and glycosaminoglycans were estimated. The levels of serum Ca2+and P increased in diabetic rats, but decreased after I or E2treatments. Serum ALP and TRAP activity increased in the ovary-intact and ovariectomized diabetic rats. Vertebral ALP activity increased in ovariectomized diabetic rats, but decreased in diabetic rats, which were treated with I or E2. In the vertebrae, TRAP activity was elevated as a result of diabetes, but this was prevented by insulin or estradiol. Diabetes induced a decrease in total collagen in the vertebrae, while I or E2treatment induced an increase. The levels of chondroitin sulphate and heparan sulphate decreased significantly in the vertebrae of both ovary-intact and ovariectomized diabetic rats, while hyaluronic acid increased. In conclusion, diabetes and ovariectomy each seem to affect the process of matrix formation and mineralization in the bone, and this is aggravated by the combination of diabetes and ovariectomy. The effects of I and E2were similar, and both hormones reversed the changes brought about by diabetes.

scholarly journals Evaluation of Antidiabetic Activity of Gymnema sylvestre and Andrographis paniculata in Streptozotocin Induced Diabetic Rats

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Prem Kumar ◽  
Sudha Rani ◽  
B Arunjyothi ◽  
P. Chakrapani ◽  
A Rojarani
Keyword(s):  
Diabetes Mellitus ◽  
Medicinal Plants ◽  
Low Cost ◽  
Diabetic Rats ◽  
Andrographis Paniculata ◽  
Antidiabetic Activity ◽  
Gymnema Sylvestre ◽  
Streptozotocin Induced Diabetes ◽  
Oxidative Effect

Diabetes mellitus is a difficult metabolic disorder that has seriously impact the human health and quality of life. Medicinal plants are being used to control diabetes However, they are not entirely effective and no one has ever been reported to have fully recovered from diabetes. Many plants have been used for the management of diabetes mellitus in various traditional systems of medicine worldwide as they are a great source of biological constituents and many of them are known to be effective against diabetes. Medicinal plants with antihyperglycemic activities are being more desired, owing to lesser sideeffects and low cost. Streptozotocin was induced to all groups of rats at dosage of 35 -55mg/kg except for the normal. Streptozotocin induced diabetes in sprague dawly rats were used to study antidiabetic activity of methonolic extract of two medicinal plants Gymnema sylvestre,Andrographis paniculata methanolic leaf extract was administered orally in graded doses of 30 mg/kg,50mg /kg sprague dawly rats Gymnema sylvestre at a dose of 30mg/kg and Andrographis paniculata at a dose of 50mg/kg showed significant anti-hyperglycemic and anti-oxidative effect which was evident from the 1st week of treatment.

The effect of Syzygium cumini (L.) skeels on post-prandial blood glucose levels in non-diabetic rats and rats with streptozotocin-induced diabetes mellitus

1997 ◽  
Vol 56 (3) ◽  
pp. 209-213 ◽  
Author(s):  
Claudio Coimbra Teixeira ◽  
Luciano Pilla Pinto ◽  
Felix Henrique Paim Kessler ◽  
Lia Knijnik ◽  
Cristiano Pilla Pinto ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Diabetic Rats ◽  
Syzygium Cumini ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Streptozotocin Induced Diabetes

scholarly journals Pharmacokinetics of Itraconazole in Diabetic Rats

2009 ◽  
Vol 54 (2) ◽  
pp. 931-933 ◽  
Author(s):  
Unji Lee ◽  
Young H. Choi ◽  
So H. Kim ◽  
Byung K. Lee
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Concentration ◽  
Oral Administration ◽  
Intrinsic Clearance ◽  
Diabetic Rats ◽  
Clearance Rates ◽  
Time Curve ◽  
Concentration Time ◽  
Streptozotocin Induced Diabetes ◽  
Plasma Concentration Time Curve

ABSTRACT After intravenous or oral administration of 10 mg/kg itraconazole to rats with streptozotocin-induced diabetes mellitus and to control rats, the total area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24) for itraconazole and that for its metabolite, 7-hydroxyitraconazole, were similar between the two groups of rats. This may be explained by the comparable hepatic and intestinal intrinsic clearance rates for the disappearance of itraconazole and the formation of 7-hydroxyitraconazole in both groups of rats.

scholarly journals Impact of Momordica charantia (karela) on serum aspartate aminotransferase level in streptozotocin induced diabetic rats

Mediscope ◽  
2015 ◽  
Vol 2 (1) ◽  
pp. 18-21
Author(s):  
S Mohal ◽  
DK Mondal ◽  
PK Chowdhury ◽  
H Biswas ◽  
A Khanom ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Aspartate Aminotransferase ◽  
Diabetic Rats ◽  
High Serum ◽  
Momordica Charantia ◽  
Significant Difference ◽  
Vehicle Injection ◽  
Serum Aspartate Aminotransferase ◽  
Streptozotocin Induced Diabetes ◽  
The Mean

The  present  experimental  study  was  conducted  to  investigate  whether  Momordica  charantia  (karela)  has  got  any  impact  on  serum  aspartate  aminotransferase  (AST)  level  in  the  streptozotocin induced diabetic rats. Sixty healthy young Long Evans rats of male sex weighing  150 to 280 gm aged between 10 to 12 weeks were used in this study. The rats were divided into  4 equal groups depending on their different sorts of dietary feedings and drug treatment. Serum  AST level was estimated in all rats up to day 51 from the day of streptozotocin/ vehicle injection.  The mean ± SD of final serum AST level as percentage of corresponding initial level (value on  51st day  to  the  value  on  7th day) was  95.1  ±  13.4  u/L  in  healthy  rats,  110.0  ±  7.6  u/L  in  the  untreated diabetic rats, 39.4 ± 10.1 u/L in the insulin-treated diabetic rats and 109.5 ± 23.8 u/L  in  the  karela-treated  diabetic  rats. The AST percentage  change  value  of  diabetic  rats  on  51st  day  corresponding  to  the  initial  on  7th day was  significantly  higher  than  that  healthy  rats  (p  <  0.01).  The  value  in  the  insulin-treated  diabetic  rats  was  significantly  lower  than  that  of  the  untreated diabetic rats (p < 0.001) and the karela-treated diabetic rats (p < 0.001). There was no  significant  difference  between  the  values  of  the  untreated  diabetic  rats  and  the  karela-treated  diabetic  rats  (p  >  0.05).  Karela showed  a  tendency  of  acting  against hyperglycemic  effects  of  streptozotocin  induced  diabetes  mellitus  and  also  acting  against  high  serum  aspartate  aminotransferase  (AST)  level  in  streptozotocin  induced  diabetes  mellitus.  However,  further  investigations  are  recommended  for  establishing  karela  as  a  safe  and  useful  effective  anti-hyperglycemic  agent  as  well  as  an  agent  acting  against  the  rise  in  serum  AST  level  in  streptozotocin induced diabetic rats.Mediscope Vol. 2, No. 1: 2015, Pages 18-21

Role of vasopressin in diabetes mellitus-induced changes in medullary transport proteins involved in urine concentration in Brattleboro rats

2004 ◽  
Vol 286 (4) ◽  
pp. F760-F766 ◽  
Author(s):  
Dongun Kim ◽  
Jeff M. Sands ◽  
Janet D. Klein
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Rats ◽  
Urine Concentration ◽  
Transport Proteins ◽  
Protein Abundance ◽  
Brattleboro Rats ◽  
Urea Transporter ◽  
Streptozotocin Induced Diabetes ◽  
Induced Changes

In rats with streptozotocin-induced diabetes mellitus for 10–20 days, we showed that the abundance of the major medullary transport proteins involved in the urinary concentrating mechanism, urea transporter (UT-A1), aquaporin-2 (AQP2), and the Na+-K+-2Cl- cotransporter (NKCC2/BSC1), is increased, despite the ongoing osmotic diuresis. To test whether vasopressin is necessary for these diabetes mellitus-induced changes in UT-A1, AQP2, or NKCC2/BSC1, we studied Brattleboro rats because they lack vasopressin. Brattleboro rats were given vasopressin (2.4 μg/day via osmotic minipump) for 5 or 12 days. At 5 days, vasopressin increased AQP2 protein abundance but decreased UT-A1 abundance compared with untreated Brattleboro rats. At 12 days, vasopressin increased the abundance of both UT-A1 and AQP2 proteins but did not alter NKCC2/BSC1. Next, untreated Brattleboro rats were made diabetic for 10 days by injecting them with streptozotocin (40 mg/kg). Diabetes mellitus increased the abundance of AQP2 and NKCC2/BSC1 proteins, but UT-A1 protein abundance did not increase. Third, vasopressin-treated Brattleboro rats were made diabetic with streptozotocin for 10 days. In vasopressin-treated Brattleboro rats, diabetes mellitus increased UT-A1, AQP2, and NKCC2/BSC1 protein abundances. Vasopressin significantly increased UT-A1 phosphorylation in vasopressin-treated diabetic Brattleboro rats but not in the other groups of Brattleboro rats. We conclude that 1) administering vasopressin to Brattleboro rats for 12 days, but not for 5 days, increases UT-A1 protein abundance and 2) vasopressin is necessary for the increase in UT-A1 protein in diabetic rats but is not necessary for the increase in AQP2 or NKCC2 proteins.

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