E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling
| Autor: | Vijay Hegde, Nikhil V. Dhurandhar, Olga Dubuisson, Ha-Na Na |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Physiology medicine.medical_treatment Glucose uptake lcsh:Medicine Biochemistry Fats Mice Endocrinology 0302 clinical medicine Cell Signaling Medicine and Health Sciences Insulin Small interfering RNAs Pyrophosphatases lcsh:Science 2. Zero hunger Glucose tolerance test Multidisciplinary biology medicine.diagnostic_test Organic Compounds Monosaccharides Flow Cytometry Lipids Insulin oscillation Nucleic acids Chemistry Infectious Diseases Adipose Tissue Physical Sciences Anatomy Rosiglitazone Research Article Signal Transduction medicine.drug medicine.medical_specialty Infectious Disease Control Immunoblotting Carbohydrates 030209 endocrinology & metabolism Carbohydrate metabolism Transfection Glucose Signaling 03 medical and health sciences Insulin resistance Internal medicine Genetics medicine Animals Non-coding RNA Diabetic Endocrinology Endocrine Physiology Phosphoric Diester Hydrolases Insulin Signaling Organic Chemistry lcsh:R Chemical Compounds Biology and Life Sciences Cell Biology Glucose Tolerance Test medicine.disease Hormones Gene regulation Mice Inbred C57BL Insulin receptor Glucose Biological Tissue 030104 developmental biology biology.protein RNA lcsh:Q Gene expression Insulin Resistance Adenovirus E4 Proteins |
| Zdroj: | PLoS ONE, Vol 11, Iss 8, p e0161275 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR), and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown) with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling. |
| Databáze: | OpenAIRE |
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