The Ancient Drug Salicylate Indirectly Targets Fructose-1,6-Bisphosphatase to Suppress Liver Glucose Production in Diet-Induced Obese Mice.

ABSTRACT:

Aims

The benefit of salicylate in the treatment of diabetes has been recognized for over a century; however, challenging side effects have prevented widespread use. A better understanding of the relevant enzyme targets mediating its anti-hyperglycaemic effect may lead to the development of novel therapies for diabetes. Here, we investigated the contribution of 5'-adenosine monophosphate (AMP)-dependent inhibition of fructose-1,6-bisphosphatase 1 (FBP1) to the anti-hyperglycaemic action of salicylate.

Methods

We studied AMP-insensitive FBP1 G27P knockin (KI) mice through a variety of cellular approaches, including proteomics, Seahorse metabolic analysis, glucose production, and other assays, in addition to a detailed assessment of metabolic responses in vivo.

Results

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SUBMITTER: Nisr RB 

PROVIDER: S-EPMC12096142 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature