Inhalation of human insulin (exubera) augments the efficiency of muscle glucose uptake in vivo.
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.
Edgerton
Dale S
DS
Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 710 Robinson Research Building, Nashville, TN, USA. dale.edgerton@vanderbilt.edu
Cherrington
Alan D
AD
Williams
Phillip
P
Neal
Doss W
DW
Scott
Melanie
M
Bowen
Larry
L
Wilson
Warren
W
Hobbs
Charles H
CH
Leach
Chet
C
Kuo
Mei-Chang
MC
Strack
Thomas R
TR
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
C473734:Exubera; D007328:Insulin; D005947:Glucose