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Thyroid Hormone Coordinates Pancreatic Islet Maturation During the Zebrafish Larval-to-Juvenile Transition to Maintain Glucose Homeostasis


Thyroid hormone (TH) signaling promotes tissue maturation and adult organ formation. Developmental transitions alter an organism's metabolic requirements, and it remains unclear how development and metabolic demands are coordinated. We used the zebrafish as a model to test whether and how TH signaling affects pancreatic islet maturation, and consequently glucose homeostasis, during the larval to juvenile transition. We found that exogenous TH precociously activates the beta-cell differentiation genes pax6b and mnx1 while downregulating arxa, a master regulator of alpha-cell development and function. Together, these effects induced hypoglycemia, at least in part by increasing insulin and decreasing glucagon expression. We visualized TH target tissues using a novel TH-responsive reporter line and found that both alpha- and beta-cells become targets of endogenous TH signaling during the larval-to-juvenile transition. Importantly, endogenous TH is required during this transition for the functional maturation of alpha- and beta-cells in order to maintain glucose homeostasis. Thus, our study sheds new light on the regulation of glucose metabolism during major developmental transitions.

Type Journal
ISBN 1939-327X (Electronic) 0012-1797 (Linking)
Authors Matsuda, H.; Mullapudi, S. T.; Zhang, Y.; Hesselson, D.; Stainier, D. Y. R.
Publisher Name DIABETES
Published Date 2017-10-01
Published Volume 66
Published Issue 10
Published Pages 2623-2635
Status Published in-print
DOI 10.2337/db16-1476
URL link to publisher's version