ACE inhibition may decrease diabetes risk by boosting the impact of bradykinin on adipocytes.
The findings of the recent HOPE trial strongly suggest that ACE inhibitor therapy may reduce risk for type 2 diabetes in patients who are non-diabetic at baseline. This finding is readily rationalized by previous evidence that bradykinin, acting via B2 receptors, can potentiate the insulin responsiveness of both adipocytes and muscle fibers; this effect may be mediated by a reduction in the activity of a tyrosine phosphatase that targets the insulin receptor. ACE inhibitors, in turn, increase the availability of bradykinin by suppressing its proteolytic degradation. In light of the fact that the development of insulin resistance in adipocytes is responsible for the excessive free fatty acid flux that gives rise to the diabetic syndrome, a favorable impact of ACE inhibition on adipocyte insulin responsiveness - complemented by a potentiation of the direct action of bradykinin on skeletal muscle - offers a satisfying explanation for the prevention of diabetes observed during ACE inhibitor therapy. Since the population at risk for diabetes is huge and increasing dramatically, the recent development of orally absorbable food-derived peptides with clinically significant ACE inhibitory activity - such as 'Katsuobushi oligopeptides' derived from bonito - may make it more logistically feasible to achieve this protection on a widescale basis, while simultaneously promoting blood pressure control and reducing risk for atherothrombotic disease.
McCarty
M F
MF
Pantox Laboratories, San Diego, California 92109, USA.
D017667:Adipocytes / Q000378:metabolism*; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001920:Bradykinin / Q000187:drug effects / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000517:prevention & control; D004198:Disease Susceptibility / Q000628:therapy; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D018570:Risk Assessment
D000806:Angiotensin-Converting Enzyme Inhibitors; D007328:Insulin; D001920:Bradykinin