Over half a billion people worldwide suffer from type 2 diabetes, a condition characterized by the body’s inability to use insulin effectively. Despite extensive research, the exact mechanisms behind this breakdown have remained elusive. Recent discoveries by researchers at Case Western Reserve University, however, may shed new light on this complex disease.1
The Role of Nitric Oxide

Nitric oxide (NO) is a molecule produced in nearly all cell types and is vital for various bodily functions, including nervous system operations, immune response, and blood vessel dilation. Jonathan Stamler and his team at Case Western Reserve University have linked NO to the body’s metabolism and type 2 diabetes through a process called S-nitrosylation.
Discovery of the SCAN Enzyme

The researchers identified a novel enzyme, SCAN (SNO-CoA-assisted nitrosylase), which plays a crucial role in S-nitrosylation. SCAN helps attach NO to target proteins like insulin receptors. In individuals with insulin resistance, SCAN activity is heightened, leading to excessive NO attachment to proteins, which disrupts insulin signaling.
Impact of SCAN on Insulin Resistance

In mouse models of diabetes, inhibiting SCAN activity prevented the development of typical diabetic symptoms. This finding suggests that hypernitrosylation, caused by excessive SCAN activity, may be a driving factor in type 2 diabetes. Targeting SCAN could therefore be a promising avenue for new treatments.2
Parallel Research at Johns Hopkins

In related research, scientists at Johns Hopkins All Children’s Hospital identified another factor contributing to type 2 diabetes: a deficiency in the cell trafficking protein PITPNA. This protein is crucial for the formation of insulin granules in pancreatic beta-cells. Restoring PITPNA levels in deficient beta-cells improved insulin production and reversed many diabetes-related deficiencies.3
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Potential for New Therapies

The discoveries at Case Western Reserve University and Johns Hopkins highlight new potential therapeutic targets for type 2 diabetes. By blocking SCAN or increasing PITPNA levels, scientists hope to restore proper insulin functionality and possibly prevent the onset of diabetes.
Future Research Directions

Further research is needed to explore the full potential of these findings. Stamler’s team plans to investigate how inhibiting SCAN can be applied in clinical settings. Meanwhile, researchers at Johns Hopkins are focusing on enhancing the functionality of stem-cell-derived pancreatic beta-cells by increasing PITPNA levels, aiming for a possible cure.
Conclusion

These groundbreaking discoveries open new avenues for understanding and treating type 2 diabetes. By targeting the molecular mechanisms involving SCAN and PITPNA, researchers hope to develop effective therapies that could significantly improve the lives of millions affected by this condition worldwide.
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Sources
- “Scientists Think They’ve Found a New Cause of Type 2 Diabetes.” Science Alert. Carly Casella. December 20, 2023.
- “New Research Sheds Light on Cause of Type 2 Diabetes.” Hopkins Medicine. September 13, 2023.
- “An enzyme that selectively S-nitrosylates proteins to regulate insulin signaling.” Cell.
Hua-Lin Zhou, et al. December 05, 2023