Peng Liu

Biggest medical discoveries

Researchers have developed a novel “smart” insulin called NNC2215 that shows promise in addressing one of the major challenges of insulin therapy for diabetes: the risk of hypoglycemia (dangerously low blood sugar)[1][2].

How NNC2215 Works

NNC2215 is an insulin molecule engineered with a glucose-sensitive switch consisting of two key components:

1. A ring-shaped macrocycle structure
2. A glucoside molecule derived from glucose

This innovative design allows NNC2215 to automatically adjust its activity based on blood glucose levels:

• When glucose is low, the glucoside binds to the ring, keeping insulin inactive
• As glucose rises, it displaces the glucoside, activating the insulin[3]

Key Advantages

Glucose-Responsive Action: NNC2215 can turn its activity on and off in response to changing blood sugar levels, unlike traditional insulin[3].

Hypoglycemia Prevention: In animal studies, NNC2215 demonstrated the ability to lower high blood glucose effectively while preventing the dangerous drops in blood sugar that can occur with regular insulin treatment[1][2].

Reversible Effect: Unlike some previous glucose-sensitive insulin approaches that irreversibly release insulin, NNC2215’s activity can be reined in when glucose levels fall[3].

Research Findings

Studies in pigs and diabetic rats showed that:

• NNC2215 was as effective as human insulin in lowering blood glucose
• It provided protection against hypoglycemia compared to a current long-acting insulin (insulin degludec)
• During a glucose challenge, NNC2215 activation corresponded to the effect of about 30% additional human insulin[1]

In one experiment, when glucose infusion was stopped:

• NNC2215 allowed glucose to drop to about 4.5 mM
• Insulin degludec caused a drop to about 3 mM (hypoglycemic range)[1]

Potential Impact

This glucose-sensitive insulin could significantly improve diabetes management by:

1. Reducing the risk of hypoglycemic events
2. Improving quality of life for people with diabetes
3. Potentially allowing for more aggressive glucose control with less fear of low blood sugar[2][3]

While further research is needed to optimize NNC2215 and assess its safety and efficacy in humans, this development represents a promising step toward more automated and safer insulin therapy for diabetes.

Citations:
[1] https://assets-eu.researchsquare.com/files/rs-2882397/v1/1e7e4dfd-92d3-4b6e-b79d-451074f743b0.pdf?c=1729149088
[2] https://www.nature.com/articles/s41586-024-08042-3
[3] https://www.nature.com/articles/d41586-024-03357-7
[4] https://www.news-medical.net/news/20241018/New-glucose-sensitive-insulin-NNC2215-could-transform-diabetes-care-by-lowering-hypoglycemia-risk.aspx
[5] https://pubmed.ncbi.nlm.nih.gov/39415004/?fc=None&ff=20241018054337&v=2.18.0.post9+e462414
[6] https://www.researchgate.net/publication/370676441_Glucose-sensitive_insulin_with_attenuation_of_hypoglycaemia
[7] https://twitter.com/MoEbrahimkhani/status/1846618934830944543
[8] https://twitter.com/DanielJDrucker/status/1846588322551902458

Recently, one of my dedicated research endeavors, titled “Emergence of Emotion Selectivity in Deep Neural Networks Trained to Recognize Visual Objects,” was published. This milestone has sparked a plethora of thoughts in my mind. Considering my increasingly reflective state, I believe it is valuable to share these insights publicly.

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1. Open Mind: I have a broad interest in various fields. In 2019, as a student focusing on medical imaging analysis, I began to explore the interactions between neuroscience and Artificial Intelligence (AI). Fortunately, I had the opportunity to discuss this with a friend who was studying neuroscience. The fascinating complexity of the human brain intrigued me, leading to thoughts on leveraging AI to understand brain functions. Our inspirational discussions convinced me that this was a path worth exploring. Gradually, a collaboration was formed between two labs (Prof. Mingzhou Ding and Prof. Ruogu Fang), and our mutual interest fueled this collaboration.
2. Efforts Over Outcomes: Starting a new path is always challenging, especially figuring out where or how to begin in a new field. We explored various approaches and directions, investing tremendous effort in this research. Most times, the process was not exciting but filled with struggles to achieve interesting results. However, I enjoyed this journey. Looking back, I appreciate the knowledge gained, the mindset changes, and the growth in strength. The most beautiful aspect is the intricate emotions developed through this challenging journey. The best way to learn and grow is through discomfort. These changes in mindset and behavior have a subtle but nuanced impact on those around you, lasting for decades and generations, which is more important than any immediate outcome (e.g., publication). This perspective suggests we should reconsider the core of learning and teaching, emphasizing effort over outcomes to inspire students to build their world with more joy and interest. It makes me wonder how my mindset changed to value effort over immediate results.
3. Challenges Arise from Simplicity: Our work was seemingly simple – identifying selective neurons for emotion in neural networks. Finding neurons that behaved differently was straightforward, but determining if they were selective for emotions alone was challenging. Could they also be selective for faces or objects? What is emotion, after all? We sought to connect human subjective feelings with artificial neurons in a limited physical space, requiring convincing evidence of these neurons’ functionality. After exploring numerous experimental developments, I finally obtained convincing evidence supporting our claims. However, the simplicity is what initially captures attention in our work.
4. The Art of Scientific Work: Creating scientific work is not always about suffering; it’s about creating art with your efforts. The more effort you put in, the more beautiful it becomes. You learn and understand more about your work, sometimes knowing little about the underlying insights even after publication. It’s ironic but true. I appreciate the changes from the inside out, affecting others who are discovering or building amazing work to address human challenges.
5. No Talent, Just Interest with a Little Perseverance: This work took many years to complete, and I never wanted to give up. We underwent two rounds of revision, and a particularly challenging but critical question arose during the last round—disentangling the effects of object category and emotion categories in selective neurons. Honestly, I wasn’t fully convinced of our discoveries until I achieved the “desired” results. Without love for the truth and perseverance in my exploration, completion would have been impossible. As I recommend to my students, the book “Grit” by Angela Duckworth is a must-read for students, educators, and parents alike.
6. Focus Matters: As mentioned, I have broad interests. However, life is short. If we could live 200 years, I would spend the first 100 exploring everything I could and the next 100 focusing on what interests me the most. Knowing this earlier would have led me to double my efforts on this work. Recently, I advised a young college student on career development and life choices, sharing my experiences and encouraging her to find and focus on what interests her most as early as possible. I explained how focusing on what truly fascinates us can lead to greater happiness and fulfillment in life. This approach counters the temptation to spread our interests too thinly, especially given the constraints of human biology and the finite nature of our existence. In a world where our understanding of others is inherently limited, honing in on our passions not only enhances our own well-being but also allows us to make more meaningful contributions within the limited space and time we have.

Each individual is unique, with their talents, characters, interests, etc. I continue to ponder how these differences impact the development of life/career paths and influence our organizations and the distribution of wealth in the long term.

This journey of exploration, marked by curiosity, challenge, and collaboration, has not only expanded my horizons but also deepened my appreciation for the intricacies of interdisciplinary research. It has taught me the invaluable lessons of perseverance, the importance of an open mind, and the transformative power of dedication. These experiences underscore the belief that the pursuit of knowledge is not solely about the destination but the journey itself. As we continue to navigate the vast and complex landscape of scientific inquiry, let us carry forward the insights gained, not just as individual achievements but as collective contributions to the broader tapestry of human understanding and progress. I am really grateful for the efforts, guidance, and support of Prof. Mingzhou Ding and Prof. Ruogu Fang.

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