Received for publication May 25, 2006.
Revised August 31, 2006.
Accepted for publication September 6, 2006.

Inhalation of human insulin is associated with improved insulin action compared with subcutaneous injection and endogenous secretion in dogs

Abstract

This study compared the effects of endogenous (portal) insulin secretion vs. peripheral insulin administration with subcutaneous (SC) or inhaled human insulin (INH; Exubera^® (insulin human [rDNA origin]) Inhalation Powder) on glucose disposal in fasted dogs. In the control group, glucose was infused into the portal vein (Endo; n = 6). In 2 other groups, glucose was infused portally, while insulin was administered peripherally by inhalation (INH; n = 13) or SC injection (SC; n = 6) with somatostatin and basal glucagon. In the Endo group, over the first 3 h, the arterial insulin concentration was twice that of the peripheral groups, whereas hepatic sinusoidal insulin levels were half as much. Although net hepatic glucose uptake was greatest in the Endo group, the peripheral groups demonstrated larger increases in nonhepatic glucose uptake so that total glucose disposal was greater in the latter groups. Compared with SC insulin action, glucose excursions were smaller and briefer and insulin action was at least twice as great following INH. Thus, at the glucose dose and insulin levels chosen, peripheral insulin delivery was associated with greater whole body glucose disposal than endogenous (portal) insulin secretion; INH administration resulted in increased insulin sensitivity in nonhepatic, but not in hepatic tissues compared with SC delivery.

Key words: diabetes, dogs, glucose disposal, glucose uptake, hepatic tissue, inhaled human insulin