Thyroid Hormone Promotes Postnatal Rat Pancreatic β-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA

被引：117

作者：

Aguayo-Mazzucato, Cristina ^{[1
]}

Zavacki, Ann Marie ^{[2
]}

Marinelarena, Alejandra ^{[1
]}

Hollister-Lock, Jennifer ^{[1
]}

El Khattabi, Ilham ^{[1
]}

Marsili, Alessandro ^{[2
]}

Weir, Gordon C. ^{[1
]}

Sharma, Arun ^{[1
]}

Larsen, P. Reed ^{[2
]}

Bonner-Weir, Susan ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens,Thyroid Sect, Boston, MA USA

来源：

DIABETES | 2013年 / 62卷 / 05期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; RECEPTOR ISOFORM; IN-VIVO; ISLETS; GENE; DEIODINASE; EXPRESSION; DIGESTION; ALPHA; MOUSE;

D O I：

10.2337/db12-0849

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Neonatal beta cells do not secrete glucose-responsive insulin and are considered immature. We previously showed the transcription factor MAFA is key for the functional maturation of beta cells, but the physiological regulators of this process are unknown. Here we show that postnatal rat beta cells express thyroid hormone (TH) receptor isoforms and deiodinases in an age-dependent pattern as glucose responsiveness develops. In vivo neonatal triiodothyronine supplementation and TH inhibition, respectively, accelerated and delayed metabolic development. In vitro exposure of immature islets to triiodothyronine enhanced the expression of Mafa, the secretion of glucose-responsive insulin, and the proportion of responsive cells, all of which are effects that were abolished in the presence of dominant-negative Mafa. Using chromatin immunoprecipitation and electrophoretic mobility shift assay, we show that TH has a direct receptor-ligand interaction with the Mafa promoter and, using a luciferase reporter, that this interaction was functional. Thus, TH can be considered a physiological regulator of functional maturation of beta cells via its induction of Mafa. Diabetes 62:1569-1580, 2013

引用

页码：1569 / 1580

页数：12

共 42 条

[1]

Mafa expression enhances glucose-responsive insulin secretion in neonatal rat beta cells [J].