Inhalation of Insulin (Exubera) Is Associated With Augmented Disposal of Portally Infused Glucose in Dogs

Inhalation of Insulin (Exubera) Is Associated With Augmented Disposal of Portally Infused Glucose in Dogs Dale S. Edgerton 1 , Doss W. Neal 1 , Melanie Scott 1 , Larry Bowen 2 , Warren Wilson 2 , Charles H. Hobbs 2 , Chet Leach 2 , Shantha Sivakumaran 3 , Thomas R. Strack 4 and Alan D. Cherrington 1 1 Vanderbilt University Medical Center, Nashville, Tennessee 2 Lovelace Respiratory Research Institute, Albuquerque, New Mexico 3 Aventis Pharmaceuticals, Bridgewater, New Jersey 4 Pfizer, New York, New York Address correspondence and reprint requests to Dale S. Edgerton, PhD, Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 710 Robinson Research Bldg., Nashville, TN 37232-0615. E-mail: dale.edgerton{at}vanderbilt.edu Abstract The results of the present study, using the conscious beagle dog, demonstrate that inhaled insulin (INH; Exubera) provides better glycemic control during an intraportal glucose load than identical insulin levels induced by insulin (Humulin) infusion into the inferior vena cava (IVC). In the INH group ( n = 13), portal glucose infusion caused arterial plasma glucose to rise transiently (152 ± 9 mg/dl), before it returned to baseline (65 min) for the next 2 h. Net hepatic glucose uptake was minimal, whereas nonhepatic uptake rose to 12.5 ± 0.5 mg · kg −1 · min −1 (65 min). In the IVC group ( n = 9), arterial glucose rose rapidly (172 ± 6 mg/dl) and transiently fell to 135 ± 13 mg/dl (65 min) before returning to 165 ± 15 mg/dl (125 min). Plasma glucose excursions and hepatic glucose uptake were much greater in the IVC group, whereas nonhepatic uptake was markedly less (8.6 ± 0.9 mg · kg −1 · min −1 ; 65 min). Insulin kinetics and areas under the curve were identical in both groups. These data suggest that inhalation of Exubera results in a unique action on nonhepatic glucose clearance. IVC, inferior vena cava NHB, net hepatic balance Footnotes Accepted January 12, 2005. Received October 27, 2004. DIABETES