Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation
| Autor: | Dorit Daphna-Iken, Barbara B. Kahn, Erwin C. Puente, Adam J. Bree, Vanessa H. Routh, Zhenyu Sheng, Simon J. Fisher, Candace M. Reno |
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| Rok vydání: | 2016 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine endocrine system diseases Endocrinology Diabetes and Metabolism Glucose uptake Indinavir Rats Sprague-Dawley Impaired glucose tolerance Mice 0302 clinical medicine Homeostasis Medicine Glucose homeostasis Mice Knockout Neurons Glucose tolerance test Glucose Transporter Type 4 medicine.diagnostic_test biology Brain Glucose clamp technique Proto-Oncogene Proteins c-fos hormones hormone substitutes and hormone antagonists medicine.medical_specialty Epinephrine Blotting Western Hypothalamus In Vitro Techniques Diet High-Fat Glucagon 03 medical and health sciences Insulin resistance Internal medicine Glucose Intolerance Internal Medicine Animals business.industry nutritional and metabolic diseases Glucose Tolerance Test medicine.disease Hypoglycemia Rats Glucose Metabolism 030104 developmental biology Endocrinology Glucose Clamp Technique biology.protein Insulin Resistance business 030217 neurology & neurosurgery GLUT4 Paraventricular Hypothalamic Nucleus |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db16-0917 |
| Popis: | GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. |
| Databáze: | OpenAIRE |
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