Enhancement of the SESN2-SHP cascade by melatonin ameliorates hepatic gluconeogenesis by inhibiting the CRBN-BTG2-CREBH signaling pathway

Experimental & Molecular Medicine, Published online: 24 July 2023; doi:10.1038/s12276-023-01040-xThe identification of a fundamental signalling process regulated by melatonin that can prevent excessive liver glucose metabolism during diabetes may offer a novel therapeutic approach. Both fasting and diabetic states trigger the elevation of a particular signalling pathway that significantly increases liver glucose metabolism, or ‘hepatic gluconeogenesis’, resulting in a rise in blood sugar levels. In experiments on mouse models and human patients, Yong Deuk Kim at Kyungpook National University in Daegu, South Korea, and co-workers have demonstrated that the hormone melatonin plays a vital role in suppressing hepatic gluconeogenesis. Melatonin upregulates another signaling cascade involving a stress regulation protein called sestrin-2 and its associated regulatory protein, SHP. The upregulation of SHP by melatonin repressed genes that are involved in gluconeogenesis, both in diabetic mice and in the human liver.
Source: Experimental and Molecular Medicine - Category: Molecular Biology Authors: Source Type: research