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(Hypertension. 2001;38:1355.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Role of the B₂ Receptor of Bradykinin in Insulin Sensitivity

Irena Duka; Sherene Shenouda; Conrado Johns; Ekaterina Kintsurashvili; Irene Gavras; Haralambos Gavras

From the Hypertension and Atherosclerosis Section of the Department of Medicine, Boston University School of Medicine, Mass.

Correspondence to Haralambos Gavras, MD, FRCP, Hypertension and Atherosclerosis Section, Boston University School of Medicine, 715 Albany St, Boston, MA 02118. E-mail hgavras{at}bu.edu

The biological actions of bradykinin (BK) are attributed to its B₂ type receptor (B₂R), whereas the B₁R is constitutively absent, inducible by inflammation and toxins. Previous studies in B₂R gene knockout mice showed that the B₁R is overexpressed, is further upregulated by hypertensive maneuvers, and assumes some of the hemodynamic functions of the B₂R. The current experiments were designed to further clarify the metabolic function of the B₂R and to explore whether the upregulated B₁R can also assume the metabolic function of the missing B₂R. One group of B₂R-/- mice (n=9) and one of B₂R+/+ controls (n=8) were treated for 3 days with captopril (which produced a similar blood pressure-lowering response in both groups) and studied with the hyperinsulinemic euglycemic clamp. The knockout mice had fasting and steady-state blood glucose levels similar to those of the wild-type mice but a had tendency to higher fasting insulin levels (at 27.8±5.2 versus 18±2.9 mU/L, respectively). However, they had significantly higher steady-state insulin levels (749±127.2 versus 429.1±31.5 mU/L, P<0.05) and a significantly lower glucose uptake rate (31±2.4 versus 41±2.3 mg/kg per minute, P<0.05) and insulin sensitivity index (4.6±0.9 versus 10±0.7 P<0.001). Analysis of B₁R and B₂R gene expression by reverse transcription-polymerase chain reaction in cardiac muscle, skeletal muscle, and adipose tissues revealed significantly higher B₁R mRNA level in the knockouts versus wild-type (P<0.05) at baseline and a further significant upregulation in mRNA by 1.8- to 3.2-fold (P<0.05) after insulin infusion. We conclude that absence of B₂R confers a state of insulin resistance because it results in impaired insulin-dependent glucose transport; this is probably a direct B₂R effect because, unlike the hemodynamic autacoid-mediated effects, it cannot be assumed by the upregulated B₁R.

Key Words: insulin • hyperinsulinism • mice • bradykinin • gene expression

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