Diagenode

DNA methylation directs functional maturation of pancreatic β cells


Dhawan S, Tschen SI, Zeng C, Guo T, Hebrok M, Matveyenko A, Bhushan A.

Pancreatic β cells secrete insulin in response to postprandial increases in glucose levels to prevent hyperglycemia and inhibit insulin secretion under fasting conditions to protect against hypoglycemia. β cells lack this functional capability at birth and acquire glucose-stimulated insulin secretion (GSIS) during neonatal life. Here, we have shown that during postnatal life, the de novo DNA methyltransferase DNMT3A initiates a metabolic program by repressing key genes, thereby enabling the coupling of insulin secretion to glucose levels. In a murine model, β cell-specific deletion of Dnmt3a prevented the metabolic switch, resulting in loss of GSIS. DNMT3A bound to the promoters of the genes encoding hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) - both of which regulate the metabolic switch - and knockdown of these two key DNMT3A targets restored the GSIS response in islets from animals with β cell-specific Dnmt3a deletion. Furthermore, DNA methylation-mediated repression of glucose-secretion decoupling genes to modulate GSIS was conserved in human β cells. Together, our results reveal a role for DNA methylation to direct the acquisition of pancreatic β cell function.

Tags
Antibody

Share this article

Published
July, 2015

Source

Products used in this publication

  • Mouse IgG
    C15400001-15
    Mouse IgG Antibodies - Chip

活动

  • AACR 2024
    San Diego, California, USA
    Apr 5-Apr 10, 2024
 查看所有活动

新闻

 查看所有新闻


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics