Functional Inactivation of DrosophilaGCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2.

ABSTRACT: Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the DrosophilaGCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products

SUBMITTER: Mascolo E 

PROVIDER: S-EPMC7831483 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature