Ricerc@Sapienza

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 Drosophila GCK orthologs Hex-A and Hex-C results in
a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin

In eukaryotes, pyridoxal kinase (PDXK) acts in vitamin B-6 salvage pathway to produce pyridoxal 5'-phosphate (PLP), the active form of the vitamin, which is implicated in numerous crucial metabolic reactions. In Drosophila, mutations in the dPdxk gene cause chromosome aberrations (CABs) and increase glucose content in larval hemolymph. Both phenotypes are rescued by the expression of the wild type human PDXK counterpart.

Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, works as cofactor in numerous enzymatic reactions and it behaves as antioxidant molecule. PLP deficiency has been associated to many human pathologies including cancer and diabetes and the mechanism behind this connection is now becoming clearer. Inadequate intake of this vitamin increases the risk of many cancers; furthermore, PLP deprivation impairs insulin secretion in rats, whereas PLP supplementation prevents diabetic complications and improves gestational diabetes.

Pyridoxine/pyridoxamine 5′‐phosphate oxidase (PNPO) and pyridoxal kinase (PDXK)
cooperate to produce pyridoxal 5′‐phosphate (PLP), the active form of vitamin B6. PDXK
phosphorylates pyridoxine, pyridoxamine, and pyridoxal by producing PNP, PMP, and PLP,
whereas PNPO oxidizes PNP, PMP, into PLP. We previously demonstrated that PDXK
depletion in Drosophila and human cells impacts on glucose metabolism and DNA integrity.
Here we characterized sgll, the Drosophila ortholog of PNPO gene, showing that its silencing

The protein phosphatase 2A (PP2A) is a conserved heterotrimeric enzyme that regulates several cellular processes including