Antihypertensive agent moxonidine enhances muscle glucose transport in insulin-resistant rats

Erik J Henriksen, Stephan Jacob, Donovan L. Fogt, Erik B. Youngblood, Jochen Gödicke

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The sympatholytic antihypertensive agent moxonidine, a centrally acting selective I1-imidazoline receptor modulator (putative agonist), may be beneficial in hypertensive patients with insulin resistance. In the present study, the effects of chronic in vivo moxonidine treatment of obese Zucker rats-a model of severe glucose intolerance, hyperinsulinemia and insulin resistance, and dyslipidemia-on whole-body glucose tolerance, plasma lipids, and insulin-stimulated skeletal muscle glucose transport activity (2- deoxyglucose uptake) were investigated. Moxonidine was administered by gavage for 21 consecutive days at 2, 6, or 10 mg/kg body weight. Body weights in control and moxonidine-treated groups were matched, except at the highest dose, at which final body weight was 17% lower in the moxonidine-treated animals compared with controls. The moxonidine-treated (6 and 10 mg/kg) obese animals had significantly lower fasting plasma levels of insulin (17% and 19%, respectively) and free fatty acids (36% and 28%, respectively), whereas plasma glucose was not altered. During an oral glucose tolerance test, the glucose response (area under the curve) was 47% and 67% lower, respectively, in the two highest moxonidine-treated obese groups. Moreover, glucose transport activity in the isolated epitrochlearis muscle stimulated by a maximally effective insulin dose (13.3 nmol/L) was 39% and 70% greater in the 6 and 10 mg/kg moxonidine-treated groups, respectively (P<.05 for all effects). No significant alterations in muscle glucose transport were elicited by 2 mg/kg moxonidine. These findings indicate that in the severely insulin-resistant and dyslipidemic obese Zucker rat, chronic in vivo treatment with moxonidine can significantly improve, in a dose-dependent manner, whole-body glucose tolerance, possibly as a result of enhanced insulin-stimulated skeletal muscle glucose transport activity and reduced circulating free fatty acids.

Original languageEnglish (US)
Pages (from-to)1560-1565
Number of pages6
JournalHypertension
Volume30
Issue number6
StatePublished - Dec 1997

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moxonidine
Antihypertensive Agents
Insulin
Glucose
Muscles
Zucker Rats
Body Weight
Nonesterified Fatty Acids
Insulin Resistance
Skeletal Muscle
Sympatholytics

Keywords

  • Glucose tolerance test
  • Imidazoline receptor modulation
  • Sympatholytics

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Henriksen, E. J., Jacob, S., Fogt, D. L., Youngblood, E. B., & Gödicke, J. (1997). Antihypertensive agent moxonidine enhances muscle glucose transport in insulin-resistant rats. Hypertension, 30(6), 1560-1565.

Antihypertensive agent moxonidine enhances muscle glucose transport in insulin-resistant rats. / Henriksen, Erik J; Jacob, Stephan; Fogt, Donovan L.; Youngblood, Erik B.; Gödicke, Jochen.

In: Hypertension, Vol. 30, No. 6, 12.1997, p. 1560-1565.

Research output: Contribution to journalArticle

Henriksen, EJ, Jacob, S, Fogt, DL, Youngblood, EB & Gödicke, J 1997, 'Antihypertensive agent moxonidine enhances muscle glucose transport in insulin-resistant rats', Hypertension, vol. 30, no. 6, pp. 1560-1565.
Henriksen, Erik J ; Jacob, Stephan ; Fogt, Donovan L. ; Youngblood, Erik B. ; Gödicke, Jochen. / Antihypertensive agent moxonidine enhances muscle glucose transport in insulin-resistant rats. In: Hypertension. 1997 ; Vol. 30, No. 6. pp. 1560-1565.
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