Improvement of Glucose Assimilation and Protein Degradation by Bradykinin in Maturity Onset Diabetics and in Surgical Patients

Wickimayr, Matthias; Dietze, G.; Günther, B.; Böttger, I.; Mayer, L.; Janetschek, P.

doi:10.1007/978-1-4757-0926-1_52

Cited by 22 publications

(9 citation statements)

References 11 publications

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“…Exogenous bradykinin infusion has been shown to decrease blood glucose levels in NIDDM probably because of an increase in peripheral blood flow and/or the insulinlike activity of bradykinin, both of which result in the acceleration of peripheral glucose disposal (Wicklmayr et al 1979;Jauch et al 1987). The DD genotype is associated with increased plasma ACE levels, and higher ACE levels may, by increasing the degradation of bradykinin, lead to lower bradykinin levels associated with glucose intolerance, as observed in the present study.…”

Section: Discussionsupporting

confidence: 76%

Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM

et al. 1998

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The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been shown to be associated with cardiovascular and renal diseases in diabetes mellitus, but the mechanism underlying this association is not known. In addition, recent studies of the effect of the ACE gene on blood pressure have yielded conflicting results. Therefore, we studied the association of the ACE gene I/D polymorphism with glucose intolerance and insulin resistance, and the contribution of this locus to genetic susceptibility to hypertension in non-insulin-dependent diabetic mellitus (NIDDM). We analysed the ACE genotype in 84 unrelated NIDDM patients with a known disease duration of less than 1 year and in 115 age- and sex-matched controls. The I/D polymorphism was determined by the polymerase chain reaction. There were no differences in ACE genotype distribution and allele frequencies between patients with NIDDM and nondiabetic controls. The frequencies of the D and I alleles in both groups were identical, viz., 0.65 and 0.35, respectively. The NIDDM patients with the DD genotype had significantly higher blood glucose levels in the oral glucose tolerance test than those with the other genotypes; the incremental glucose area under the curve in the order of II, ID, and DD was 7.2+/-2.4, 9.2+/-4.0, and 10.7+/-2.7 mmol/l x h (II vs ID vs DD, P=0.0066 by ANOVA). No significant difference was found between the ACE genotype and serum insulin values. Similarly, there were no differences in body mass index, blood pressure, or serum lipids between the three genotypes. Among the non-diabetic controls, there was no statistically significant association of the I/D polymorphism with serum lipids, blood glucose levels, serum insulin concentrations, or blood pressure values. In conclusion, NIDDM patients with the DD genotype have higher blood glucose levels and are more glucose intolerant; this may help to explain the reported association between the D allele and vascular complications in NIDDM.

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Section: Discussionsupporting

confidence: 76%

Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM

et al. 1998

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“…kg-1. min-1 had a positive effect on insulin sensitivity in insulin-resistant post-operative and NIDDM patients without any systemic haemodynamic changes [30]. Therefore, plasma bradykinin concentrations after captopril administration might have a significant role in the improvement of insulin sensitivity.…”

Section: Discussionmentioning

confidence: 92%

Effect on insulin sensitivity of angiotensin converting enzyme inhibitors with or without a sulphydryl group: bradykinin may improve insulin resistance in dogs and humans

et al. 1994

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SummaryThe present study compared the effect on insulin sensitivity of ACE inhibitors with a sulphydryl group (captopril) or those without a sulphydryl group (delapril and enalapril) during the hyperinsulinaemic euglycaemic clamp test in both animal and clinical experiments. A possible contribution of bradykinin to the improvement of insulin sensitivity by ACE-inhibition was also studied. In healthy control and depancreatized dog experiments, administration of captopril either intravenously (3.0 mmol. kg-1) or orally (5.0 mmolkg-1) increased insulin sensitivity indices and plasma bradykinin concentrations. In comparison, intravenous administration of an active metabolite of delapril (3.0 mmol. kg -1) and oral administration of either delapril or enalapril (5.0 mmol.kg -1) showed slight, but not significant increases in insulin sensitivity indices and plasma bradykinin concentrations. Infusion of a bradykinin antagonist (N-a-adamantaneacetyl-DArg-[Hyp3,ThiJ.8,D-Phe 7]-bradykinin) (0.5 nmol. kg-1. min -1) abolished the effect of captopril on insulin sensitivity. Furthermore, intravenous administration of bradykinin (0.1 nmol. kg-1. min-1) increased insulin sensitivity indices. In clinical experiments, insulin sensitivity indices decreased in the following order: normotensive healthy subjects, hypertensive non-diabetic patients, normotensive NIDDM patients and hypertensive NIDDM patients. In these four groups, oral administration of captopril (2.0 mmol. kg-1) significantly increased insulin sensitivity indices, and a concomitant increase in plasma bradykinin concentrations was observed. By contrast, oral administration of enalapril or delapril showed slight, but not significant effects on insulin sensitivity indices and plasma bradykinin concentrations. From these studies, it is concluded that ACE inhibitors with a sulphydryl group have more potent action on the improvement in insulin sensitivity than those without a sulphydryl group. Bradykinin may also possibly be involved in the mechanism underlying the improvement in insulin sensitivity associated with ACE-inhibition. [Diabetologia (1994) 37: 300-307]

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“…1 It is also known to play an important role in glucose metabolism. 2,3 Indeed, it was shown in vitro and in vivo that administration of bradykinin increases the glucose uptake in cultured adipocytes 4 as well as in long-term rat experiments 5 and in skeletal muscle of human forearm. 6 ACE inhibitors were shown to improve glucose utilization, 7 an action that is attributed to bradykinin.…”

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confidence: 99%

Role of the B ₂ Receptor of Bradykinin in Insulin Sensitivity

et al. 2001

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Abstract-The biological actions of bradykinin (BK) are attributed to its B 2 type receptor (B 2 R), whereas the B 1 R is constitutively absent, inducible by inflammation and toxins. Previous studies in B 2 R gene knockout mice showed that the B 1 R is overexpressed, is further upregulated by hypertensive maneuvers, and assumes some of the hemodynamic functions of the B 2 R. The current experiments were designed to further clarify the metabolic function of the B 2 R and to explore whether the upregulated B 1 R can also assume the metabolic function of the missing B 2 R. One group of B 2 RϪ/Ϫ mice (nϭ9) and one of B 2 Rϩ/ϩ controls (nϭ8) 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 27.8Ϯ5.2 versus 18Ϯ2.9 mU/L, respectively). However, they had significantly higher steady-state insulin levels (749Ϯ127. radykinin mediates a variety of biological effects such as vasodilation, vascular permeability, inflammation, pain, and edema. 1 It is also known to play an important role in glucose metabolism. 2,3 Indeed, it was shown in vitro and in vivo that administration of bradykinin increases the glucose uptake in cultured adipocytes 4 as well as in long-term rat experiments 5 and in skeletal muscle of human forearm. 6 ACE inhibitors were shown to improve glucose utilization, 7 an action that is attributed to bradykinin. 8,9 In keeping with these data, kininogen-deficient rats were found to be resistant to insulin. 10 The effects of bradykinin are mediated by the B 1 -or B 2 -type receptor (B 1 R or B 2 R). It has been accepted that almost all of the physiologically significant effects of bradykinin, including the metabolic ones, are exerted by activation of the B 2 R. Indeed, inhibition of the B 2 R by various antagonists was shown to reverse the amelioration of insulindependent glucose transport by ACE inhibitors, 11,12 whereas blockade of downstream mediators, such as prostaglandins and NO, had no effect on insulin sensitivity. 12 Several studies have shown that the B 2 R is expressed in tissues dependent on insulin for glucose uptake, such as skeletal muscle and adipocytes. 4,13,14 On the contrary, the B 1 R is not expressed under normal conditions; it has long been known that its expression is induced by toxins or inflammatory mediators and it contributes to endotoxic shock, 15 but it has not been associated with metabolic functions.In a recent series of studies, investigators have used genetically engineered mice with deleted B 2 R 16 to further explore the physiological actions of bradykinin. Using these mice, we observed that the B 1 R is highly expressed in B 2 R knockout mice and appears to take over some of the hemodynamic properties of the B 2 R. 17 The present experiments were designed to further explore the metabolic function of t...

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Improvement of Glucose Assimilation and Protein Degradation by Bradykinin in Maturity Onset Diabetics and in Surgical Patients

Cited by 22 publications

References 11 publications

Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM

Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM

Effect on insulin sensitivity of angiotensin converting enzyme inhibitors with or without a sulphydryl group: bradykinin may improve insulin resistance in dogs and humans

Role of the B ₂ Receptor of Bradykinin in Insulin Sensitivity

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Improvement of Glucose Assimilation and Protein Degradation by Bradykinin in Maturity Onset Diabetics and in Surgical Patients

Cited by 22 publications

References 11 publications

Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM

Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM

Effect on insulin sensitivity of angiotensin converting enzyme inhibitors with or without a sulphydryl group: bradykinin may improve insulin resistance in dogs and humans

Role of the B 2 Receptor of Bradykinin in Insulin Sensitivity

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Role of the B ₂ Receptor of Bradykinin in Insulin Sensitivity