Modulation of insulin activity by hydrochloride salts

The influence of hydrochloride salts of various amino acids and other drugs on the activity of exogenously administered insulin was studied in the rat. Insulin activity was assessed in terms of insulin's effects on lowering of blood glucose and nonesterified fatty acids (NEFA), release of adrenaline (epinephrine) from the adrenal medulla, and the elevation of urinary catecholamines. Insulin alone produced a 60-70% fall in blood glucose and NEFA, 70% depletion of adrenal epinephrine, a 10-fold increase in urinary epinephrine, and a 2-fold elevation of adrenal dopamine. Concurrent administration of hydrochloride salts completely abolished all clinical manifestations that usually accompany insulin injection. Serum glucose and NEFA remained unchanged, the fall in adrenal epinephrine was blocked, and the increase in urinary catecholamines was abolished. These data suggest that certain hydrochloride salts possess an anti-insulin property. They decrease tissue responsiveness to insulin, thus rendering its action ineffective. The implication of these findings on the treatment of diabetic subjects requiring insulin therapy is discussed.