Targeting GFAT for diabetes management: a therapeutic approach to alleviate hexosamine pathway-induced complications

Year 2025, Volume: 38 Issue: 1, 1 - 8, 29.01.2025

Ishwarya Obilineni Vadivelan Ramachandran , Harshini Magesh

Abstract

Diabetes mellitus (DM) is one of the leading non-communicable metabolic disorders. Over time it may lead to the development of
serious complications. Glutamine fructose-6-phosphate amidotransferase (GFAT), is the first and rate-limiting enzyme that plays an
important role in regulating the hexosamine biosynthesis pathway (HBP). During hyperglycemia, excess glucose that enters the cell
gets diverted into the HBP by this GFAT enzyme. Recent studies have suggested that the overexpression of GFAT is associated with
insulin resistance and diabetic complications and it is mainly seen in patients with diabetes.
Using various sources, an extensive literature survey was conducted to determine the complex role of GFAT enzyme and
their involvement in the modification of various proteins and transcription factors, contributing to the development of diabetes
complications.
The overexpression of GFAT during hyperglycemia increases the flux through the HBP, resulting in insulin resistance, and various
vascular complications such as nephropathy, neuropathy, retinopathy, delayed wound healing, and cardiovascular complications.
Inhibiting GFAT emerges as a potential therapeutic strategy to counteract hexosamine pathway-induced insulin resistance and
alleviate vascular complications in diabetes. The multifaceted role of GFAT in diabetic complications underscores its significance as a
therapeutic target for future advancements in diabetes management.

Keywords

GFAT, Diabetes, Hexosamine pathway, Insulin resistance, Diabetic complications

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