1. Insulin induces a hypercontractile airway smooth muscle phenotype
- Author
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Mechteld M. Grootte Bromhaar, S. Adriaan Nelemans, Herman Meurs, Reinoud Gosens, Johan Zaagsma, Maartje Hiemstra, and Molecular Pharmacology
- Subjects
medicine.medical_specialty ,insulin ,SYMPTOMS ,phenotype ,medicine.medical_treatment ,CHILDREN ,In Vitro Techniques ,Organ culture ,Culture Media, Serum-Free ,Potassium Chloride ,MITOGENESIS ,SERUM ,Contractility ,air-way smooth muscle ,Isometric Contraction ,Diabetes mellitus ,Internal medicine ,KINASE ,Animals ,Medicine ,Insulin-Like Growth Factor I ,M-2 MUSCARINIC RECEPTORS ,Methacholine Chloride ,Pancreatic hormone ,Platelet-Derived Growth Factor ,Pharmacology ,Dose-Response Relationship, Drug ,Epidermal Growth Factor ,diabetes ,TYPE-1 DIABETES-MELLITUS ,business.industry ,Insulin ,TRACHEA ,Drug Synergism ,Muscle, Smooth ,DNA ,asthma ,medicine.disease ,In vitro ,PROOF-OF-CONCEPT ,Endocrinology ,medicine.anatomical_structure ,CELLS ,Cattle ,Methacholine ,business ,Muscle Contraction ,medicine.drug ,Respiratory tract - Abstract
This study aims to investigate the effects of insulin on bovine tracheal smooth muscle phenotype in vitro. Contractility of muscle strips and DNA-synthesis ([3 H]thymidine incorporation) of isolated cells were used as parameters for smooth muscle phenotyping. Insulin (1 muM) 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. (C) 2003 Elsevier B.V. All rights reserved.
- Published
- 2003