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.

journal_name

Diabetes

journal_title

Diabetes

authors

Edgerton DS,Cherrington AD,Williams P,Neal DW,Scott M,Bowen L,Wilson W,Hobbs CH,Leach C,Kuo MC,Strack TR

doi

10.2337/db06-0718

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

3604-10

issue

12

eissn

0012-1797

issn

1939-327X

pii

55/12/3604

journal_volume

55

pub_type

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