title: 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 versus peripheral insulin administration with subcutaneous 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 two other groups, glucose was infused portally, whereas insulin was administered peripherally by inhalation (n = 13) or s.c. injection (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 s.c. insulin action, glucose excursions were smaller and shorter, and insulin action was at least twice as great after 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 s.c. delivery.
authors.affiliation: Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 710 Robinson Research Building, Nashville, TN 37232-0615, USA. dale.edgerton@vanderbilt.edu
authors.forename: Dale S
authors.initials: DS
authors.lastname: Edgerton
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Stettler
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: Thomas R
authors.initials: TR
authors.lastname: Strack
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004285:Dogs; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin