Intracrine Testosterone Activation in Human Pancreatic β-Cells Stimulates Insulin Secretion.

Xu, Weiwei, Schiffer, Lina, Qadir, M M Fahd, Zhang, Yanqing, Hawley, James, Mota De Sa, Paula, Keevil, Brian G, Wu, Hongju, Arlt, Wiebke and Mauvais-Jarvis, Franck (2020) Intracrine Testosterone Activation in Human Pancreatic β-Cells Stimulates Insulin Secretion. Diabetes. ISSN 1939-327X. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

Full text not available from this repository.
Official URL: http://diabetes.diabetesjournals.org/

Abstract

Testosterone (T) affects β-cell function in men and women. T is a prohormone that undergoes intracrine conversion in target tissues to the potent androgen dihydrotestosterone (DHT) via the enzyme 5α-reductase (5α-R) or to the active estrogen 17β-estradiol (E2) via the aromatase enzyme. Using male and female human pancreas sections, we show that the 5α-R type 1 isoform (SRD5A1) and aromatase are expressed in male and female β-cells. We show that cultured male and female human islets exposed to T produce DHT and downstream metabolites. In these islets, exposure to the 5α-R inhibitors finasteride and dutasteride inhibited T conversion into DHT. We did not detect T conversion into E2 from female islets. However, we detected T conversion into E2 in islets from two out of four male donors. In these donors, exposure to the aromatase inhibitor anastrozole inhibited E2 production. Notably, in cultured male and female islets, T enhanced glucose-stimulated insulin secretion (GSIS). In these islets, exposure to 5α-R inhibitors or the aromatase inhibitor both inhibited T enhancement of GSIS. In conclusion, male and female human islets convert T into DHT and E2 via the intracrine activities of SRD5A1 and aromatase. This process is necessary for T enhancement of GSIS.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QT Human physiology
QU Biochemistry
WK Endocrine system. Endocrinology
Divisions: Ambulatory Care > Diabetes
Related URLs:
Depositing User: Jamie Edgar
Date Deposited: 16 Sep 2020 09:48
Last Modified: 16 Sep 2020 09:48
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3425

Actions (login required)

View Item View Item