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Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation.

Citation
Reno, C. M., et al. “Brain Glut4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, And Impaired Hypoglycemic Counterregulation.”. Diabetes, pp. 587-597.
Center Washington University in St Louis
Author Candace M Reno, Erwin C Puente, Zhenyu Sheng, Dorit Daphna-Iken, Adam J Bree, Vanessa H Routh, Barbara B Kahn, Simon J Fisher
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 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.

Year of Publication
2017
Journal
Diabetes
Volume
66
Issue
3
Number of Pages
587-597
Date Published
12/2017
ISSN Number
1939-327X
DOI
10.2337/db16-0917
Alternate Journal
Diabetes
PMID
27797912
PMCID
PMC5319720
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