CA8 emerges as a possible two-organ ‘brake’ on type 2 diabetes

Mouse studies suggest the inactive carbonic anhydrase protein helps coordinate glucose production in the liver and insulin release in the pancreas, although human research is still needed.

Researchers at Kyoto University have identified carbonic anhydrase VIII, or CA8, as a potential new target in type 2 diabetes after finding that the protein appears to help coordinate glucose control in both the liver and the pancreas. The work, reported in a study summary from News Medical, builds on the idea that high blood sugar in diabetes reflects a breakdown in two linked processes: the liver produces too much glucose, while pancreatic beta cells release too little insulin after meals. CA8 is unusual because, although it belongs to the carbonic anhydrase family, databases from the National Center for Biotechnology Information and UniProt note that it lacks the enzyme activity typical of that group.

In experiments on mice lacking functional CA8, the Kyoto team examined insulin secretion, glucose production, calcium responses and gene activity in isolated pancreatic islets and liver cells. The researchers found that the protein was enriched in islets and hepatocytes, suggesting it may act as a shared molecular brake in both tissues. When CA8 was missing, glucose output from the liver rose and insulin secretion in response to glucose also increased, pointing to a complex, tissue-specific role rather than a simple on-off switch. UniProt describes CA8 as a broadly expressed protein with notable activity in the liver, while NCBI gene records link the CA8 gene to several other biological and clinical associations.

The study also suggests a possible explanation for part of the growing interest in glucagon-based diabetes therapies. According to the Kyoto researchers, prolonged exposure to glucagon increased CA8 expression, which then reduced the response to further glucagon stimulation. In other words, CA8 may help desensitise cells to the very hormone that drives the liver to release glucose. That finding could matter because it points to a shared intracellular pathway that links hepatic glucose production with pancreatic hormone release, rather than treating them as separate problems.

The findings are promising, but they remain early-stage. Much of the evidence comes from mouse experiments, and the researchers said work in human tissues and cells will be needed before CA8 can be considered a viable therapeutic target. Still, the study highlights a broader shift in diabetes research towards coordinated, multi-organ treatment strategies. As first author Muhammad Fauzi put it, “We were intrigued that a single intracellular regulator could act as a common ‘brake’ in two organs but produce very different physiological outcomes.” Corresponding author Takaaki Murakami added, “Our findings may help explain part of the complexity of this disease.”