期刊
DIABETES OBESITY & METABOLISM
卷 11, 期 11, 页码 1050-1059出版社
WILEY
DOI: 10.1111/j.1463-1326.2009.01096.x
关键词
animal study; diabetes therapy; GLP-1 Technosphere Inhalation Powder; glucagon-like peptide 1; incretin; insulin secretion; pharmacodynamic; pharmacokinetic; pulmonary administration
资金
- MannKind Corporation
Aim The feasibility of administering native glucagon-like peptide 1 (GLP-1) as GLP-1 Technosphere (R) Inhalation Powder for diabetes therapy has been demonstrated in a rat model. Methods GLP-1 Technosphere Inhalation Powders containing 5, 10 and 15% GLP-1 were prepared and administered to healthy female Sprague-Dawley rats and to male Zucker diabetic obese rats. Rats received a single dose of GLP-1 Technosphere Powder by pulmonary insufflation. GLP-1 pharmacokinetic and pharmacodynamic responses were measured. Results Maximum circulating GLP-1 concentrations were achieved at similar to 10 min after dosing with detectable levels at 40 min. In a food consumption study, Sprague-Dawley rats receiving GLP-1 Technosphere Powder once-daily consumed less food than control rats for up to 24 h after dosing. Cumulative food consumption was decreased approximately 10% after 78 h. In an intraperitoneal glucose tolerance test, Zucker diabetic fatty rats receiving 2 mg GLP-1 Technosphere Powder (0.3 mg GLP-1) by pulmonary insufflation exhibited lower glucose concentrations and higher insulin concentrations than control rats. Pancreatic evaluations showed no differences in apoptotic index or cell proliferation of beta-cells. In addition, a dose-related increase in insulin expression within the pancreas was observed. Conclusions These data demonstrate the feasibility of administering native GLP-1 as GLP-1 Technosphere Inhalation Powder for diabetes therapy.
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