Effect of chronic bradykinin administration on insulin action in an animal model of insulin resistance

Erik J Henriksen, Stephan Jacob, Donovan L. Fogt, Guenther J. Dietze

Research output: Contribution to journalArticle

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Abstract

The nonapeptide bradykinin (BK) has been implicated as the mediator of the beneficial effect of angiotensin-converting enzyme inhibitors on insulin- stimulated glucose transport in insulin-resistant skeletal muscle. In the present study, the effects of chronic in vivo BK treatment of obese Zucker (fa/fa) rats, a model of glucose intolerance and severe insulin resistance, on whole body glucose tolerance and skeletal muscle glucose transport activity stimulated by insulin or contractions were investigated. BK was administered subcutaneously (twice daily at 40 μg/kg body wt) for 14 consecutive days. Compared with a saline-treated obese group, the BK-treated obese animals had significantly (P <0.05) lower fasting plasma levels of insulin (20%) and free fatty acids (26%), whereas plasma glucose was not different. During a 1 g/kg body wt oral glucose tolerance test, the glucose and insulin responses [incremental areas under the curve (AUC)] were 21 and 29% lower, respectively, in the BK-treated obese group. The glucose-insulin index, the product of the glucose and insulin AUCs and an indirect index of in vivo insulin action, was 52% lower in the BK-treated obese group compared with the obese control group. Moreover, 2-deoxyglucose uptake in the isolated epitrochlearis muscle stimulated by a maximally effective dose of insulin (2 mU/ml) was 52% greater in the BK-treated obese group. Contraction-stimulated (10 tetani) 2-deoxyglucose uptake was also enhanced by 35% as a result of the BK treatment. In conclusion, these findings indicate that in the severely insulin-resistant obese Zucker rat, chronic in vivo treatment with BK can significantly improve whole body glucose tolerance, possibly as a result of the enhanced insulin-stimulated skeletal muscle glucose transport activity observed in these animals.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume275
Issue number1 44-1
StatePublished - Jul 1998

Fingerprint

Bradykinin
Insulin Resistance
Animal Models
Insulin
Glucose
Skeletal Muscle
Deoxyglucose
Area Under Curve
Zucker Rats
Glucose Intolerance
Tetanus
Glucose Tolerance Test
Angiotensin-Converting Enzyme Inhibitors
Nonesterified Fatty Acids
Fasting
Muscles
Control Groups

Keywords

  • Contractions
  • Glucose tolerance
  • Kinins
  • Muscle glucose transport activity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Effect of chronic bradykinin administration on insulin action in an animal model of insulin resistance. / Henriksen, Erik J; Jacob, Stephan; Fogt, Donovan L.; Dietze, Guenther J.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 275, No. 1 44-1, 07.1998.

Research output: Contribution to journalArticle

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