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- Title
Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation.
- Authors
Reno, Candace M.; Puente, Erwin C.; Zhenyu Sheng; Daphna-Iken, Dorit; Bree, Adam J.; Routh, Vanessa H.; Kahn, Barbara B.; Fisher, Simon J.; Sheng, Zhenyu
- Abstract
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.
- Subjects
PROTEINS; ADIPOSE tissues; GLUCOSE; INSULIN; HYPOGLYCEMIA; PROTEIN metabolism; BRAIN metabolism; GLUCOSE metabolism; ADRENALINE; ANIMAL experimentation; BIOLOGICAL models; BLOOD sugar; CARRIER proteins; DIET; GLUCAGON; GLUCOSE tolerance tests; HOMEOSTASIS; HYPOTHALAMUS; INSULIN resistance; MICE; NEURONS; RATS; RESEARCH funding; WESTERN immunoblotting; GLUCOSE intolerance; INDINAVIR; IN vitro studies; GLUCOSE clamp technique; PHARMACODYNAMICS
- Publication
Diabetes, 2017, Vol 66, Issue 3, p587
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-0917