title: Inhalation of human insulin (exubera) augments the efficiency of muscle glucose uptake in vivo.
abstract: This study assessed the site of increased glucose uptake resulting from insulin inhalation, quantified its effect under steady-state glucose concentrations, and identified the time to onset of effect. Human insulin was administered to 13 beagles via inhalation (Exubera [insulin human (rDNA origin)] Inhalation Powder; n = 7) or infusion into the inferior vena cava (Humulin R; n = 6) using an algorithm to match plasma insulin levels and kinetics for both groups. Somatostatin and glucagon were infused. Glucose was delivered into the portal vein (4 mg x kg(-1) x min(-1)) and a peripheral vein, as needed, to maintain arterial plasma glucose levels at 180 mg/dl. Hepatic exposure to insulin and glucose and liver glucose uptake were similar in both groups. Despite comparable arterial insulin and glucose levels, hind-limb glucose uptake increased 2.4-fold after inhalation compared with infusion due to increased muscle glucose uptake. Glucose infusion rate, nonhepatic glucose uptake, and tracer-determined glucose disposal were about twice as great compared with intravenous insulin. The effect appeared after 1 h, persisting at least as long as arterial insulin levels remained above basal. Pulmonary administration of insulin increases nonhepatic glucose uptake compared with infusion, and skeletal muscle is the likely site of that effect.
authors.affiliation: Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 710 Robinson Research Building, Nashville, TN, USA. dale.edgerton@vanderbilt.edu
authors.forename: Dale S
authors.initials: DS
authors.lastname: Edgerton
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
authors.forename: Phillip
authors.initials: P
authors.lastname: Williams
authors.forename: Doss W
authors.initials: DW
authors.lastname: Neal
authors.forename: Melanie
authors.initials: M
authors.lastname: Scott
authors.forename: Larry
authors.initials: L
authors.lastname: Bowen
authors.forename: Warren
authors.initials: W
authors.lastname: Wilson
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hobbs
authors.forename: Chet
authors.initials: C
authors.lastname: Leach
authors.forename: Mei-Chang
authors.initials: MC
authors.lastname: Kuo
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Strack
mesh_terms: D000280:Administration, Inhalation; D000465:Algorithms; D005215:Fasting; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
chemical_list: C473734:Exubera; D007328:Insulin; D005947:Glucose