A new study published in Life Metabolism has uncovered a surprising player in how the body manages blood sugar after meals—an enzyme called hyaluronidase-1 (HYAL1). Researchers from Baylor College of Medicine and the University of Namur found that HYAL1 plays a key role in controlling glucose production in the liver, particularly following food intake. This discovery opens up potential new pathways for treating metabolic conditions such as type 2 diabetes, where the body struggles to maintain normal blood sugar levels.
The study focused on hyaluronan (HA), a sugar-like molecule that naturally increases in the bloodstream after eating. HA is best known for its roles in tissue structure and inflammation. However, this research reveals a new function: HA may be involved in regulating how the liver produces glucose. The liver normally reduces glucose production after meals, but in people with diabetes, this process—called gluconeogenesis—often remains overactive, contributing to high blood sugar levels.
HYAL1 is responsible for breaking down HA in the liver. When the researchers used genetically modified mice that lacked the Hyal1 gene, the animals showed increased glucose production, especially when fed a high-fat diet. In contrast, increasing HYAL1 levels in the liver improved glucose tolerance and significantly reduced gluconeogenesis, even in insulin-resistant mice.
Digging deeper, the researchers discovered how HYAL1 affects this process at the cellular level. When HYAL1 breaks down HA, it reduces the availability of a molecule called UDP-GlcNAc. This, in turn, lowers a modification process called O-GlcNAcylation on mitochondrial proteins, which are important for producing cellular energy (ATP). With reduced ATP, the liver has less fuel to support excess glucose production.
What makes this discovery especially exciting is that HYAL1 continues to function effectively even when insulin signaling is impaired, as in type 2 diabetes. This means that targeting HYAL1 could provide a new treatment strategy that works independently of insulin pathways.
While further research is needed to fully understand the impact of this mechanism, the findings offer a fresh perspective on blood sugar control. By highlighting the role of HA and HYAL1 in post-meal glucose regulation, this study paves the way for innovative approaches to managing diabetes and improving metabolic health.
