| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Wang, Xiao-Qi Lee, Sarah Wilson, Heather Seeger, Mark Iordanov, Hristo Gatla, Nandita Whittington, Adam Bach, Daniel Lu, Jian-yun Paller, Amy S. |
| Description |
Country affiliation: United States Author Affiliation: Wang XQ ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Lee S ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Wilson H ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Seeger M ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Iordanov H ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Gatla N ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Whittington A ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Bach D ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Lu JY ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.); Paller AS ( Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.) |
| Abstract |
Ganglioside GM3 mediates adipocyte insulin resistance, but the role of GM3 in diabetic wound healing, a major cause of morbidity, is unclear. The purpose of this study was to determine whether GM3 depletion promotes diabetic wound healing and directly activates keratinocyte (KC) insulin pathway signaling. GM3 synthase (GM3S) expression is increased in human diabetic foot skin, ob/ob and diet-induced obese diabetic mouse skin, and in mouse KCs exposed to increased glucose. GM3S knockout in diet-induced obese mice prevents the diabetic wound-healing defect. KC proliferation, migration, and activation of insulin receptor (IR) and insulin growth factor-1 receptor (IGF-1R) are suppressed by excess glucose in wild-type cells, but increased in GM3S (-/-) KCs with supplemental glucose. Co-immunoprecipitation of IR, IR substrate 1 (IRS-1), and IGF-1R, and increased IRS-1 and Akt phosphorylation accompany receptor activation. GM3 supplementation or inhibition of IGF-1R or PI3K reverses the increased migration of GM3S(-/-) KCs, whereas IR knockdown only partially suppresses migration. |
| File Format |
HTM / HTML |
| ISSN |
0022202X |
| e-ISSN |
15231747 |
| DOI |
10.1038/jid.2013.532 |
| Journal |
Journal of Investigative Dermatology |
| Issue Number |
5 |
| Volume Number |
134 |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2014-05-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Dermatology Diabetes Mellitus, Type 2 Metabolism G(m3) Ganglioside Insulin-like Growth Factor I Receptor, Insulin Wound Healing Physiology Animals Cell Movement Deficiency Insulin Receptor Substrate Proteins Keratinocytes Cytology Mice Mice, 129 Strain Mice, Inbred C57bl Mice, Knockout Obesity Phosphatidylinositol 3-kinases Receptor, Igf Type 1 Sialyltransferases Genetics Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology Dermatology |
