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Publication
Loss of Nuclear and Membrane Estrogen Receptor-a Differentially Impairs Insulin
Secretion and Action in Male and Female Mice.
Authors Allard C, Morford JJ, Xu B, Salwen B, Xu W, Desmoulins L, Zsombok A, Kim JK,
Levin ER, Mauvais-Jarvis F
Submitted By Submitted Externally on 4/15/2019
Status Published
Journal Diabetes
Year 2019
Date Published 3/1/2019
Volume : Pages 68 : 490 - 501
PubMed Reference 30305367
Abstract Estrogens favor glucose homeostasis primarily through the estrogen receptor-a
(ERa), but the respective importance of nuclear ERa (NOER) and membrane ERa
(MOER) pools to glucose homeostasis are unknown. We studied glucose homeostasis,
insulin secretion, and insulin sensitivity in male and female mice expressing
either the NOER or the MOER. Male and female MOER mice exhibited fasting and fed
hyperglycemia and glucose intolerance. Female MOER mice displayed impaired
central insulin signaling associated with hyperinsulinemia and insulin
resistance due to unrestrained hepatic gluconeogenesis, without alterations in
glucose-stimulated insulin secretion (GSIS). In contrast, male MOER mice did not
exhibit detectable insulin resistance, but showed impaired GSIS associated with
reduced brain glucose sensing. Female NOER mice exhibited milder hepatic insulin
resistance and glucose intolerance. In conclusion, nuclear ERa signaling is
predominant in maintaining glucose homeostasis in mice of both sexes. Lack of
nuclear ERa alters the central control of insulin sensitivity in females and
predominantly impairs the central regulation of insulin secretion in males.





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