Increased tissue kallikrein levels in type 2 diabetes

Diabetologia. 2010 Apr;53(4):779-85. doi: 10.1007/s00125-009-1645-8. Epub 2010 Jan 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Cardiotonic Agents / blood
  • Coronary Artery Bypass
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / surgery
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Immunohistochemistry
  • RNA, Messenger / genetics
  • Tissue Kallikreins / blood*
  • Tissue Kallikreins / genetics


  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiotonic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • RNA, Messenger
  • Tissue Kallikreins