HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Edgerton, D. S. Articles by Strack, T. R. Search for Related Content PubMed PubMed Citation Articles by Edgerton, D. S. Articles by Strack, T. R. Social Bookmarking                What's this?

Inhalation of Human Insulin (Exubera) Augments the Efficiency of Muscle Glucose Uptake In Vivo

¹ Vanderbilt University Medical Center, Nashville, Tennessee
² Lovelace Respiratory Research Institute, Albuquerque, New Mexico
³ Nektar Therapeutics, San Carlos, California
⁴ Pfizer, Inc., 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 Building, Nashville, TN. E-mail: dale.edgerton{at}vanderbilt.edu

Abbreviations: ATII, angiotensin II; AUC, area under the curve; BK₂, bradykinin receptor subtype 2; GIR, glucose infusion rate; IVC, inferior vena cava; MAP, mean arterial blood pressure

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 · kg^–1 · 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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. E. Fineberg, T. T. Kawabata, D. Finco-Kent, R. J. Fountaine, G. L. Finch, and A. S. Krasner Immunological Responses to Exogenous Insulin Endocr. Rev., October 1, 2007; 28(6): 625 - 652. [Abstract] [Full Text] [PDF]