Antihyperglycemic action of angiotensin II receptor antagonist, valsartan, in streptozotocin-induced diabetic rats

Paul Chan, Kar L. Wong, I. M. Liu, Thing Fong Tzeng, Tzu L. Yang, Juei Tang Cheng

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Objectives: In the present study, we use valsartan, a highly selective antagonist for angiotensin1 (AT1) receptor subtype, to investigate the effect of AT1 receptor on the plasma glucose metabolism in streptozotocin-induced diabetic rats (STZ-diabetic rats). Methods: The plasma glucose concentration was assessed by glucose oxidase method and plasma insulin was measured using enzyme-linked immunosorbent assay. Systolic blood pressure (SBP) was determined by the tail-cuff method. The intravenous glucose challenge test (IVGCT) was carried out to evaluate the effect of valsartan on the glucose utilization in vivo. The mRNA levels of the subtype 4 form of glucose transporter (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver were detected by Northern blotting analysis. Moreover, the protein levels of GLUT4 in isolated soleus muscle and hepatic PEPCK were investigated using Western blotting analysis. Results: A single intravenous injection of valsartan decreased the plasma glucose concentrations in a dose-dependent manner in STZ-diabetic rats. Plasma glucose-lowering action of valsartan also observed in normal rats although in a way not so effective as that in STZ-diabetic rats. Valsartan at the dose of 0.2 mg/kg that produced the maximal plasma glucose-lowering activity in STZ-diabetic rats is also effective to lower the SBP. However, oral treatment with nifedipine or nicorandil in STZ-diabetic rats at the dose sufficient to decrease SBP showed no change of plasma glucose. Otherwise, infusion of saralasin (10 μg/kg per min) into STZ-diabetic rats produced a plasma glucose-lowering activity similar to that by valsartan at 0.2 mg/kg. Moreover, valsartan (0.2 mg/kg) significantly attenuated the raise of plasma glucose induced by IVGCT in normal rats. Repeated intravenous administration of valsartan (0.2 mg/kg) in STZ-diabetic rats resulted in the lowering of plasma glucose after 3 days. The mRNA and protein levels of GLUT4 in the soleus muscle were increased after repeated intravenous administration of valsartan in STZ-diabetic rats for 3 days. Moreover, similar repeated treatment with valsartan reversed the elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. Conclusions: These results suggest that the plasma glucose-lowering activity of AT1 receptor antagonism was associated with an increase in the glucose utilization in peripheral tissue and/or a reduction in hepatic gluconeogenesis in the absence of insulin.

Original languageEnglish
Pages (from-to)761-769
Number of pages9
JournalJournal of Hypertension
Volume21
Issue number4
DOIs
Publication statusPublished - Apr 1 2003

Fingerprint

Valsartan
Angiotensin Receptor Antagonists
Streptozocin
Hypoglycemic Agents
Glucose
Blood Pressure
Phosphoenolpyruvate
Glucose Transporter Type 4
Skeletal Muscle
Liver
Intravenous Administration
Messenger RNA

Keywords

  • Angiotensin
  • Intravenous glucose challenge test
  • Phosphoenolpyruvate carboxykinase
  • Streptozotocin-induced diabetic rats
  • Subtype 4 form of glucose transporter
  • Valsartan

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine

Cite this

Antihyperglycemic action of angiotensin II receptor antagonist, valsartan, in streptozotocin-induced diabetic rats. / Chan, Paul; Wong, Kar L.; Liu, I. M.; Tzeng, Thing Fong; Yang, Tzu L.; Cheng, Juei Tang.

In: Journal of Hypertension, Vol. 21, No. 4, 01.04.2003, p. 761-769.

Research output: Contribution to journalArticle

Chan, Paul ; Wong, Kar L. ; Liu, I. M. ; Tzeng, Thing Fong ; Yang, Tzu L. ; Cheng, Juei Tang. / Antihyperglycemic action of angiotensin II receptor antagonist, valsartan, in streptozotocin-induced diabetic rats. In: Journal of Hypertension. 2003 ; Vol. 21, No. 4. pp. 761-769.
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AU - Wong, Kar L.

AU - Liu, I. M.

AU - Tzeng, Thing Fong

AU - Yang, Tzu L.

AU - Cheng, Juei Tang

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N2 - Objectives: In the present study, we use valsartan, a highly selective antagonist for angiotensin1 (AT1) receptor subtype, to investigate the effect of AT1 receptor on the plasma glucose metabolism in streptozotocin-induced diabetic rats (STZ-diabetic rats). Methods: The plasma glucose concentration was assessed by glucose oxidase method and plasma insulin was measured using enzyme-linked immunosorbent assay. Systolic blood pressure (SBP) was determined by the tail-cuff method. The intravenous glucose challenge test (IVGCT) was carried out to evaluate the effect of valsartan on the glucose utilization in vivo. The mRNA levels of the subtype 4 form of glucose transporter (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver were detected by Northern blotting analysis. Moreover, the protein levels of GLUT4 in isolated soleus muscle and hepatic PEPCK were investigated using Western blotting analysis. Results: A single intravenous injection of valsartan decreased the plasma glucose concentrations in a dose-dependent manner in STZ-diabetic rats. Plasma glucose-lowering action of valsartan also observed in normal rats although in a way not so effective as that in STZ-diabetic rats. Valsartan at the dose of 0.2 mg/kg that produced the maximal plasma glucose-lowering activity in STZ-diabetic rats is also effective to lower the SBP. However, oral treatment with nifedipine or nicorandil in STZ-diabetic rats at the dose sufficient to decrease SBP showed no change of plasma glucose. Otherwise, infusion of saralasin (10 μg/kg per min) into STZ-diabetic rats produced a plasma glucose-lowering activity similar to that by valsartan at 0.2 mg/kg. Moreover, valsartan (0.2 mg/kg) significantly attenuated the raise of plasma glucose induced by IVGCT in normal rats. Repeated intravenous administration of valsartan (0.2 mg/kg) in STZ-diabetic rats resulted in the lowering of plasma glucose after 3 days. The mRNA and protein levels of GLUT4 in the soleus muscle were increased after repeated intravenous administration of valsartan in STZ-diabetic rats for 3 days. Moreover, similar repeated treatment with valsartan reversed the elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. Conclusions: These results suggest that the plasma glucose-lowering activity of AT1 receptor antagonism was associated with an increase in the glucose utilization in peripheral tissue and/or a reduction in hepatic gluconeogenesis in the absence of insulin.

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KW - Streptozotocin-induced diabetic rats

KW - Subtype 4 form of glucose transporter

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