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Project acronym:   GlucoAdjust

Project type:   PRISM

Grant agreement No.:   HF-190

Project is funded by:   Science Fund of the Republic of Serbia (Belgrade, Serbia)

Instituions where the research is conducted:

  • Institut za molekularnu genetiku i genetsko inženjerstvo (Belgrade, Serbia) – Coordination
  • University of Belgrade - Faculty of Chemistry (Belgrade, Serbia) – Beneficiary
  • Medicinski fakultet (Belgrade, Serbia) – Beneficiary

Project realization is scheduled from January 1, 2024 till December 31, 2026.

Project staff

Short description of the project

Translocation of glucose-6-phosphate (G6P) by glucose-6-posphate translocase (G6PT) is considered the rate-determining step in glucose release by hepatocytes and other cell types. Therefore, G6PT plays a crucial role in the regulation of blood glucose levels and represents an attractive target for therapeutic intervention for diseases in which blood glucose homeostasis is disturbed. Two extreme human conditions are: naturally occurring hypoglycemia in glycogen storage disease type Ib (GSD Ib) and hyperglycemia in diabetes mellitus type 2 (DM type 2). Although the number of people with rare genetic disease GSD Ib is small, finding specific treatment for a rare disease is a priority recognized by United Nations. In 2040 more than half a billion people will have diabetes (95% of them type 2) and therefore a new successful strategy for their treatment is urgently needed.


To tackle these health challenges, an interdisciplinary team will screen large library of small molecule compounds (SMs) and select those that directly bind to G6PT. SMs able to stabilize G6PT and increase its function are potential drugs for GSD Ib, while those that inhibit G6PT may be used in DM type 2 treatment. The effect of selected SMs will be thoroughly evaluated in human hepatocyte models for GSD Ib and DM type 2 differentiated from GSD Ib patient-specific iPSC and Diabetic Human Adipose Derived Stem Cells respectively. To properly evaluate SM effect, a new knowledge about RNA expression related to molecular processes disturbed due to G6PT deficiency in human hepatocytes (such as ER stress, apoptosis, glycogen formation, glycogen-selective autophagy etc) will be generated and specific RNA markers for reliable preclinical in vitro drug testing will be selected for the first time. Thus, a completely new concept of using GSD Ib as a model of hypoglycemia to better adjust DM type 2 treatment is proposed here.