title: Insulin stimulates integrin-linked kinase in UMR-106 cells: potential role of heparan sulfate on syndecan-1.
abstract: Insulin plays a wide variety of physiological actions in osteoblast cells such as differentiation and gene expression. Integrins are transmembrane heterodimeric proteins consisting of α and β subunits which transduce signals from extracellular matrix into the cell. The integrin-mediated signals regulate gene expression, differentiation and survival of osteoblast. In the present study, we explored to determine if insulin could regulate integrin-linked kinase (ILK) signaling in osteoblast like UMR-106 cells. Insulin rapidly stimulated ILK activity in a time-dependent manner with maximal activity observed at 60 min. The insulin's ability to stimulate ILK was almost completely abolished when the cells were pre-incubated with heparinase III (HepIII), suggesting the heparan sulfates attached to syndecan-1 play an important role in the activation of ILK in response to insulin. Interestingly, insulin also activated Akt activity by phosphorylation, whereas pre-treatment of HepIII failed to interfere Akt activation by insulin. In contrast, HepIII pre-treatment inhibited alkaline phosphatase stimulation and collagen synthesis in response to insulin. These results strongly suggest that heparan sulfates on the syndecan-1 and/or shedding of syndecan-1 play a significant role in regulating ILK by insulin, and thereby regulating alkaline phosphatase and collagen synthesis in osteoblast cells.
authors.affiliation: a Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory , School of Dentistry, Kyung Hee University , Seoul , Republic of Korea.
authors.forename: Sae Hee
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: a Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory , School of Dentistry, Kyung Hee University , Seoul , Republic of Korea.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Ramalingam
authors.affiliation: a Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory , School of Dentistry, Kyung Hee University , Seoul , Republic of Korea.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D006497:Heparan Sulfate / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D053668:Syndecan-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000099200:Scaffold Protein ILK
chemical_list: D006497:Heparan Sulfate; D007004:Hypoglycemic Agents; D007328:Insulin; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D053668:Syndecan-1; D000099200:Scaffold Protein ILK
keywords: Heparinase III; ILK; insulin; osteoblasts; syndecan-1