Loss of nuclear and membrane estrogen receptor-a differentially impairs insulin secretion and action in Male and female mice

Camille Allard, Jamie J. Morford, Beibei Xu, Benjamin Salwen, Weiwei Xu, Lucie Desmoulins, Andrea Zsombok, Jason K. Kim, Ellis R. Levin, Franck Mauvais-Jarvis

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)490-501
Number of pages12
JournalDiabetes
Volume68
Issue number3
DOIs
StatePublished - Mar 1 2019

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Nuclear Envelope
Estrogen Receptors
Insulin
Glucose
Insulin Resistance
Homeostasis
Glucose Intolerance
Gluconeogenesis
Liver
Hyperinsulinism
Hyperglycemia
Fasting
Estrogens
Membranes
Brain

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Loss of nuclear and membrane estrogen receptor-a differentially impairs insulin secretion and action in Male and female mice. / Allard, Camille; Morford, Jamie J.; Xu, Beibei; Salwen, Benjamin; Xu, Weiwei; Desmoulins, Lucie; Zsombok, Andrea; Kim, Jason K.; Levin, Ellis R.; Mauvais-Jarvis, Franck.

In: Diabetes, Vol. 68, No. 3, 01.03.2019, p. 490-501.

Research output: Contribution to journalArticle

Allard, C, Morford, JJ, Xu, B, Salwen, B, Xu, W, Desmoulins, L, Zsombok, A, Kim, JK, Levin, ER & Mauvais-Jarvis, F 2019, 'Loss of nuclear and membrane estrogen receptor-a differentially impairs insulin secretion and action in Male and female mice', Diabetes, vol. 68, no. 3, pp. 490-501. https://doi.org/10.2337/db18-0293
Allard, Camille ; Morford, Jamie J. ; Xu, Beibei ; Salwen, Benjamin ; Xu, Weiwei ; Desmoulins, Lucie ; Zsombok, Andrea ; Kim, Jason K. ; Levin, Ellis R. ; Mauvais-Jarvis, Franck. / Loss of nuclear and membrane estrogen receptor-a differentially impairs insulin secretion and action in Male and female mice. In: Diabetes. 2019 ; Vol. 68, No. 3. pp. 490-501.
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