Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin
Autor: | Philip J. Bilan, Amira Klip, Javier R. Jaldin-Fincati, Rafaela Vaz Sousa Pereira |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment government.form_of_government Adipose tissue Endocytosis 03 medical and health sciences Physiology (medical) Internal medicine medicine Humans Hypoglycemic Agents Insulin Receptor Cells Cultured Lymphatic Vessels Skin biology Chemistry Autophosphorylation Endothelial Cells Receptor Insulin Lymphatic Endothelium Insulin receptor 030104 developmental biology Endocrinology Lymphatic system Adipose Tissue Microvessels government biology.protein Blood Vessels Endothelium Vascular |
Zdroj: | American journal of physiology. Endocrinology and metabolism. 315(2) |
ISSN: | 1522-1555 |
Popis: | Whereas the blood microvasculature constitutes a biological barrier to the action of blood-borne insulin on target tissues, the lymphatic microvasculature might act as a barrier to subcutaneously administrated insulin reaching the circulation. Here, we evaluate the interaction of insulin with primary microvascular endothelial cells of lymphatic [human dermal lymphatic endothelial cells (HDLEC)] and blood [human adipose microvascular endothelial cells (HAMEC)] origin, derived from human dermal and adipose tissues, respectively. HDLEC express higher levels of insulin receptor and signal in response to insulin as low as 2.5 nM, while HAMEC only activate signaling at 100 nM (a dose that blood vessels do not normally encounter). Low insulin acts specifically through the insulin receptor, while supraphysiological insulin acts through both the IR and insulin growth factor-1 receptor. At supraphysiological or injection site-compatible doses pertinent to lymphatic microvessels, insulin enters HAMEC and HDLEC via fluid-phase endocytosis. Conversely, at physiologically circulating doses (0.2 nM) pertinent to blood microvessels, insulin enters HAMEC through a receptor-mediated process requiring IR autophosphorylation but not downstream insulin signaling. At physiological doses, internalized insulin is barely degraded and is instead released intact to the extracellular medium. In conclusion, we document for the first time the mechanism of interaction of insulin with lymphatic endothelial cells, which may be relevant to insulin absorption during therapeutic injections. Furthermore, we describe distinct action and uptake routes for insulin at physiological and supraphysiological doses in blood microvascular endothelial cells, providing a potential explanation for previously conflicting studies on endothelial insulin uptake. |
Databáze: | OpenAIRE |
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