Insulin induces a hypercontractile airway smooth muscle phenotype.
This study aims to investigate the effects of insulin on bovine tracheal smooth muscle phenotype in vitro. Contractility of muscle strips and DNA-synthesis ([3H]thymidine incorporation) of isolated cells were used as parameters for smooth muscle phenotyping. Insulin (1 microM) was mitogenic for bovine tracheal smooth muscle and potentiated DNA-synthesis induced by other growth factors. In contrast, after pretreatment of unpassaged bovine tracheal smooth muscle cells in culture, the mitogenic response induced by growth factors was strongly diminished, with no difference in the basal incorporation. Pretreatment of bovine tracheal smooth muscle strips in organ culture with insulin increased maximal contraction to methacholine and KCl. These results show that insulin acutely augments DNA-synthesis in the presence of other growth factors. In contrast, insulin pretreatment induces a hypercontractile phenotype with a decreased mitogenic capacity. This mechanism may be involved in the putative negative association between asthma and type I diabetes. In addition, these findings may have implications for the use of aerosolized insulin in diabetes mellitus.
Gosens
Reinoud
R
Department of Molecular Pharmacology, University Centre for Pharmacy, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. R.Gosens@farm.rug.nl
Nelemans
S Adriaan
SA
Hiemstra
Maartje
M
Grootte Bromhaar
Mechteld M
MM
Meurs
Herman
H
Zaagsma
Johan
J
D000818:Animals; D002417:Cattle; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D016895:Culture Media, Serum-Free; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D016210:Methacholine Chloride; D004815:Epidermal Growth Factor; D011189:Potassium Chloride; D007334:Insulin-Like Growth Factor I; D004247:DNA