Novel studies on Drosophila melanogaster model reveal the roles of JNK-Jak/STAT axis and intestinal microbiota in insulin resistance

Abstract

The JNK pathway play a critical role in insulin resistance induced by a long-term high-sugar diet. However, the roles of up- and downstream molecules of the JNK pathway in insulin resistance are less known in vertebrates and invertebrates. As a classical organism in biological research, Drosophila melanogaster (D. melanogaster) has been widely applied to the studies of mechanism of insulin resistance. Based on previous studies, we found a novel predictive mechanism of the formation of insulin resistance in D. melanogaster. We found that JNK activated by high-sugar diet and dysregulated intestinal microbiota could mediate inflammation, and then the activated JNK released Upd3, which in turn stimulated Jak/STAT pathway to release ImpL2. ImpL2 can compete with Drosophila insulin-like peptides (Dilps) for binding with the insulin receptor and inhibit the activation of insulin pathway. In this study, we reviewed novel studies on the insulin signalling pathway based on the D. melanogaster model. The findings support our hypothesis. We, therefore, described how a long-term high-sugar diet disrupts intestinal microbiota to induce inflammation and the disruption of JNK-Jak/STAT axis. This description may offer some new clues to the formation of insulin resistance.

Keywords:

• Drosophila melanogaster
• Type 2 diabetes mellitus
• Insulin resistance
• JNK pathway
• Intestinal microbiota

Authors’ contributions

Qinghao Meng contributed to conceptualisation, writing-original draft. Yidong Xu and Ying Li contributed to formal analysis. Yiwen Wang contributed to conceptualisation, writing-review and editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Tianjin Research Innovation Project for Postgraduate Students.