Increased tissue kallikrein levels in type 2 diabetes

Duncan J Campbell, A Kladis, Yuan Zhang, A J Jenkins, D L Prior, Michael Yii, J F Kenny, Mary Jane Black, Darren J Kelly

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: We measured components of the kallikrein-kinin system in human type 2 diabetes mellitus and the effects of statin therapy on the circulating kallikrein-kinin system. METHODS: Circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, as well as plasma and tissue kallikrein, and kallistatin were measured in non-diabetic and diabetic patients before coronary artery bypass graft surgery. Tissue kallikrein levels in atrial tissue were examined by immunohistochemistry and atrial tissue kallikrein mRNA quantified. RESULTS: Plasma levels of tissue kallikrein were approximately 62 higher in diabetic than in non-diabetic patients (p = 0.001), whereas no differences were seen in circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, or in plasma kallikrein or kallistatin. Immunohistochemistry revealed a twofold increase in tissue kallikrein levels in atrial myocytes (p = 0.015), while tissue kallikrein mRNA levels were increased eightfold in atrial tissue of diabetic patients (p = 0.014). Statin therapy did not change any variables of the circulating kallikrein-kinin system. Neither aspirin, calcium antagonists, beta blockers or long-acting nitrate therapies influenced any kallikrein-kinin system variable. CONCLUSIONS/INTERPRETATION: Tissue kallikrein levels are increased in type 2 diabetes, whereas statin therapy does not modify the circulating kallikrein-kinin system. Cardiac tissue kallikrein may play a greater cardioprotective role in type 2 diabetic than in non-diabetic patients and contribute to the benefits of ACE inhibitor therapy in type 2 diabetic patients. However, our findings do not support a role for the kallikrein-kinin system in mediating the effects of statin therapy on endothelial function.
Original languageEnglish
Pages (from-to)779 - 785
Number of pages7
JournalDiabetologia
Volume53
Issue number4
DOIs
Publication statusPublished - 2010

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