1. The problem: where do the proteins localize?
Beta cells in the pancreas produce the hormone insulin, which regulates the blood glucose level in our bodies. In diabetes, the beta cells have lost part or all of their function. Although diabetes type 2 can be kept under control by making small modifications in the lifestyle, it still has no cure. Recent studies have highlighted the involvement of aquaporins (AQPs) in metabolic disorders, such as diabetes, obesity, and liver disease (1).
AQPs comprise a family of 13 members of water channels that facilitate the rapid transport of water across cell membranes. Several AQPs have been identified in the pancreas playing an essential role in the onset of insulin resistance and type 2 diabetes. In particular, AQP9 has been identified as a potential drug target in type 2 diabetes (2).
Specifically, an improved glucose control has been observed in tests on knockout mice, where AQP9 has been removed. So, less AQP9 better glucose control.
Researchers developing a new therapeutic target for patients with type 2 diabetes were looking for information about AQP9 expression in human tissues. They soon realized the information and the data available in the scientific literature were incomplete, confusing, and puzzling.
They came to us with many doubts and questions, such as:
- The majority of the studies were based on rodents.
- The data obtained from the same species was contradicting
- The primary antibodies used were not specific.
- In general, the identified locations of AQP9 expression in rodents and humans were not entirely consistent between studies. While these discrepancies may in part be explained by species differences, it is not without precedence that immunolocalization studies describe inconsistent observations as the result of false-positive identifications based on an incorrect interpretation of antibody reactivity.
- Another problem was that the antibodies against AQP9 used in various studies were not proven to be specific or validated in particular experimental conditions. The lack of specific antibodies resulted in a diffuse AQP9 expression across different tissue with no clear tissue or cell-type localization.
In simple words, the question was: where is the AQP9 protein expressed?