A study co-led by IDIBGI reveals a new biological pathway related to insulin resistance

An international study co-led by the Institute for Biomedical Research of Girona Dr. Josep Trueta (IDIBGI) has identified a new biological pathway involved in insulin resistance, one of the central mechanisms in diabetes. The work has been published in the prestigious scientific journal Proceedings of the National Academy of Sciences (PNAS), and focuses on the role of circulating ATG7 protein in the regulation of glucose metabolism and inter-organ communication.

The research was driven by a team from China Medical University, the University of Cambridge, and the Nutrition, Eumetabolism, and Health group at IDIBGI and CIBERObn. One of the corresponding authors is the leader of this research group, Dr. José Manuel Fernández-Real, and Dr. José María Moreno-Navarrete, a senior researcher from the same IDIBGI and CIBERObn group, also participated in the study.

Diabetes and insulin resistance remain a global public health challenge, closely related to the rise in obesity and other metabolic disorders. Insulin is an essential hormone that helps maintain blood glucose levels within normal ranges.

Insulin resistance occurs when cells in the muscle, adipose tissue, and liver do not respond adequately to this hormone. This hinders glucose uptake and can lead to the development of type 2 diabetes. This study shows that the ATG7 protein, traditionally associated with cellular autophagy or “internal recycling” processes, also has another key function that influences the body’s response to insulin and glucose regulation.

“This would be a completely novel mechanism, previously undetected,” highlights Dr. Moreno-Navarrete. “This study helps us understand in greater detail some of the biological processes that are altered in insulin resistance, inherent both to type 2 diabetes mellitus and to other metabolic disorders,” notes Dr. Fernández-Real.

Specifically, the research demonstrates that the ATG7 protein participates in communication between organs that play a key role in controlling blood glucose concentrations, such as the liver and muscle, two main actors in glucose utilization and storage.

The team also observed that when insulin resistance is present, the transport and function of the ATG7 protein are altered. The research detected a relationship between ATG7 levels and obesity, as higher concentrations of this protein have been identified in people with obesity, whereas physical exercise reduces these levels. This finding reinforces the role of muscle as the source of this protein and its influence on hepatic carbohydrate metabolism.

Additionally, the study identifies an ATG7-derived peptide, named Aap2, which in animal models of type 1 and type 2 diabetes reproduces the effects of the ATG7 protein on glucose metabolism. The authors emphasize that these findings provide new knowledge about diabetes biology and open future therapeutic and research avenues focused on modulating this biological pathway to improve insulin response. “What is truly unusual is that both type 1 and type 2 diabetes patients could benefit,” concludes Dr. Fernández-Real.

Dr. José Manuel Fernández-Real, head of the Nutrition, Eumetabolism, and Health research group at IDIBGI and CIBERObn, is also head of the Endocrinology Section at the Dr. Josep Trueta University Hospital, as well as professor and dean of the Faculty of Medicine at the University of Girona, and an ICREA Academia researcher.

Reference article: Guan Y, Yu Y, Fu M, Xu H, Lee E, Wang H, Moreno-Navarrete JM, Deng C, Li Y, Song K, Guo Q, Jiang X, Song X, Guo W, Feng Y, Yi F, Bai N, Li J, Chen J, Shen W, Yu W, Wang D, Hou S, Tan J, Fernández-Real JM, Vidal-Puig A, Cao L. Enhanced insulin signaling via circulating ATG7: A potential therapeutic strategy for diabetes. Proc Natl Acad Sci U S A. 2026 Jan 6;123(1):e2503783123. doi: 10.1073/pnas.2503783123. Epub 2025 Dec 29. PMID: 41461029; PMCID: PMC12773708