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

Author:

Edgerton Dale S.1,Neal Doss W.1,Scott Melanie1,Bowen Larry2,Wilson Warren2,Hobbs Charles H.2,Leach Chet2,Sivakumaran Shantha3,Strack Thomas R.4,Cherrington Alan D.1

Affiliation:

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

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.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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