Extranuclear Actions of the Androgen Receptor Enhance Glucose-Stimulated Insulin Secretion in the Male

被引：132

作者：

Navarro, Guadalupe ^{[2
]}

Xu, Weiwei ^{[1
]}

Jacobson, David A. ^{[3
]}

Wicksteed, Barton ^{[4
,5
]}

Allard, Camille ^{[1
]}

Zhang, Guanyi ^{[6
]}

De Gendt, Karel ^{[7
]}

Kim, Sung Hoon ^{[8
]}

Wu, Hongju ^{[1
]}

Zhang, Haitao ^{[6
]}

Verhoeven, Guido ^{[7
]}

Katzenellenbogen, John A. ^{[8
]}

Mauvais-Jarvis, Franck ^{[1
,2
]}

机构：

[1] Tulane Univ, Hlth Sci Ctr, Sect Endocrinol & Metab, Diabet Discovery Res & Gender Med Lab,Dept Med, New Orleans, LA 70112 USA

[2] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60611 USA

[3] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA

[4] Univ Chicago, Sect Endocrinol Diabet & Metab, Kovler Diabet Ctr, Chicago, IL 60637 USA

[5] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[6] Tulane Canc Ctr, Sch Med, Dept Pathol & Lab Med, New Orleans, LA 70112 USA

[7] Catholic Univ Louvain, Dept Clin & Expt Med, Lab Clin & Expt Endocrinol, Gasthuisberg, B-3000 Louvain, Belgium

[8] Univ Illinois, Dept Chem, Urbana, IL 61801 USA

来源：

CELL METABOLISM | 2016年 / 23卷 / 05期

关键词：

PANCREATIC BETA-CELLS; HORMONE-BINDING GLOBULIN; GENE-EXPRESSION; DEPRIVATION THERAPY; ESTROGEN-RECEPTORS; COMPLEMENTARY-DNA; PROSTATE-CANCER; OLDER MEN; IN-VITRO; TESTOSTERONE;

D O I：

10.1016/j.cmet.2016.03.015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Although men with testosterone deficiency are at increased risk for type 2 diabetes (T2D), previous studies have ignored the role of testosterone and the androgen receptor (AR) in pancreatic beta cells. We show that male mice lacking AR in beta cells (beta ARKO) exhibit decreased glucose-stimulated insulin secretion (GSIS), leading to glucose intolerance. The AR agonist dihydrotestosterone (DHT) enhances GSIS in cultured male islets, an effect that is abolished in beta ARKO(-/y) islets and human islets treated with an AR antagonist. In beta cells, DHT-activated AR is predominantly extranuclear and enhances GSIS by increasing islet cAMP and activating the protein kinase A. In mouse and human islets, the insulinotropic effect of DHT depends on activation of the glucagon-like peptide-1 (GLP-1) receptor, and accordingly, DHT amplifies the incretin effect of GLP-1. This study identifies AR as a novel receptor that enhances beta cell function, a finding with implications for the prevention of T2D in aging men.

引用

页码：837 / 851

页数：15

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