INSULIN CONCENTRATIONS AND INSULIN SENSITIVITY AFTER SHORT-TERM AMILORIDE IN HEALTHY-SUBJECTS

We have evaluated the short-term effects of amiloride on insulin actio n in vivo, since amiloride is known to impair insulin action in vitro. Seven healthy subjects were treated according to a randomized, double -blind, cross-over protocol. The treatment periods were 3 days each wi th amiloride 15 mg daily and placebo. Insulin action on glucose turnov er was assessed directly after each treatment period with the hyperins ulinaemic euglycaemic glucose clamp technique. At the two insulin conc entrations studied (similar to 30 mU.1(-1) and similar to 200 mU.1(-1) ), the glucose infusion rate required to maintain constant euglycaemia did not differ after either amiloride or placebo. The rates of glucos e production and utilization were also similar whereas the so-called i nsulin sensitivity index at the lower insulin concentration was signif icantly reduced (by about 15%) after amiloride. Moreover, amiloride pr oduced significantly higher fasting insulin and C-peptide concentratio ns, whereas fasting glucose and NEFA concentrations were unaltered. In conclusion, these data suggest that short-term amiloride slightly imp airs insulin sensitivity with respect to glucose uptake. However, over all glucose homoeostasis does not appear to be affected, probably due to a compensatory rise in plasma insulin.