Effect of aprotinin on insulin sensitivity in non-insulin-dependent diabetes mellitus.
It has been suggested that kallikrein-kinin system may influence carbohydrate metabolism via a kinin-mediated increment of insulin-mediated glucose uptake. To evaluate the effect of acute inhibition of the kallikrein-kinin system on insulin sensitivity, a randomized, placebo-controlled, double-blind study was performed in 15 male non-insulin-dependent diabetic patients. After basal evaluation of insulin sensitivity with a 2-h euglycaemic hyperinsulinaemic clamp (40 mU m-2 min-1), patients were infused either with aprotinin (200,000 U.I.C. as intravenous bolus injection) or placebo (10 ml isotonic saline) in a cross-over fashion, at 1 week intervals. After both saline and aprotinin infusions, insulin sensitivity was reassessed by continuing the euglycaemic hyperinsulinaemic clamp for a further 1 h. Resulting data showed that aprotinin significantly improved total glucose uptake (from 16.2 +/- 2.9 mumol kg min-1 to 20.6 +/- 4.9 mumol kg min-1 p < 0.01), and decreased metabolic clearance rate of insulin (from 586 +/- 57 ml m-2 min-1 to 442 +/- 155 ml m-2 min-1, p < 0.05). Thus, in spite of the suggested positive effects of kinins on insulin-mediated glucose uptake, acute inhibition of the kallikrein-kinins system resulted in a paradoxical increment of insulin sensitivity, which was probably mediated by the reduced metabolic clearance rate of insulin.
Laurenti
O
O
University La Sapienza, Institute of I Clinica Medica, Roma, Italy.
Piccoli
A
A
Bravi
C
C
Cassone-Faldetta
M
M
Bellini
C
C
Leoni
L
L
Ferri
C
C
De Mattia
G
G
D000328:Adult; D007611:Aprotinin / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004311:Double-Blind Method; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin