Enhanced glucose transport, but not phosphorylation capacity, ameliorates lipopolysaccharide-induced impairments in insulin stimulated-muscle glucose uptake
| Autor: | Yolanda F. Otero, Kimberly X. Mulligan, David H. Wasserman, Haihong Zong, Jeffrey E. Pessin, Tammy M. Barnes, Eric A. Ford, Owen P. McGuinness, Carlo M. Malabanan |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Blood Glucose Lipopolysaccharides medicine.medical_specialty medicine.medical_treatment Glucose uptake PDK4 Muscle Proteins 030204 cardiovascular system & hematology Critical Care and Intensive Care Medicine Article 03 medical and health sciences Mice 0302 clinical medicine Insulin resistance Internal medicine Medicine Animals Insulin Glycolysis Phosphorylation Muscle Skeletal Glucose Transporter Type 4 biology business.industry Glucose transporter Skeletal muscle medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Emergency Medicine biology.protein business hormones hormone substitutes and hormone antagonists GLUT4 Glycogen |
| Popis: | Lipopolysaccharide (LPS) is known to impair insulin stimulated muscle glucose uptake. We determined if increased glucose transport (GLUT4) or phosphorylation capacity (hexokinase II; HKII) could overcome the impairment in muscle glucose uptake (MGU). We utilized mice that over-expressed GLUT4 (GLUT4Tg) or HKII (HKTg) in skeletal muscle. Studies were performed in conscious, chronically catheterized (carotid artery and jugular vein) mice. Mice received an intravenous bolus of either LPS (10μg/g body weight) or vehicle (VEH). After 5 h, a hyperinsulinemic-euglycemic clamp was performed. As MGU is also dependent on cardiovascular function that is negatively affected by LPS, cardiac function was assessed using echocardiography. LPS decreased whole body glucose disposal and MGU in WT and HKTg mice. In contrast, the decrease was attenuated in GLUT4Tg mice. While membrane-associated GLUT4 was increased in VEH-treated GLUT4Tg mice, LPS impaired membrane-associated GLUT4in GLUT4Tg mice to the same level as LPS-treated WT mice. This suggested that overexpression of GLUT4 had further benefits beyond preserving transport activity. In fact, GLUT4 overexpression attenuated the LPS-induced decrease in cardiac function. The maintenance of MGU in GLUT4Tg mice following LPS was accompanied by sustained anaerobic glycolytic flux as suggested by increased muscle Pdk4 expression, and elevated lactate availability. Thus, enhanced glucose transport, but not phosphorylation capacity, ameliorates LPS-induced impairments in MGU. This benefit is mediated by long-term adaptations to the overexpression of GLUT4 that sustain muscle anaerobic glycolytic flux and cardiac function in response to LPS. |
| Databáze: | OpenAIRE |
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