Type 2 diabetes mellitus (T2DM) primarily occurs due to insulin resistance and dysfunction of pancreatic beta cells, leading to insufficient insulin secretion. Patients typically exhibit the classic symptoms of 'polydipsia, polyphagia, polyuria, and emaciation' ('three polys and one deficit') as they cannot effectively utilize insulin. On the other hand, type 1 diabetes mellitus (T1DM) is characterized by an absolute deficiency of insulin caused by the destruction of pancreatic islet beta cells. This destruction results in diabetes, usually diagnosed during childhood or adolescence, although it can also occur in adulthood. It's worth noting that diabetes resulting from specific causes of beta cell destruction is not classified as type 1 diabetes.
According to the International Diabetes Federation (IDF) 2021's 'Global Diabetes Atlas (10th edition),' global spending on diabetes and related treatments reached a staggering $996 billion in 2021, with over 50% of this expenditure allocated to treating diabetes-related complications. Moreover, the economic losses due to diabetes globally are even higher, with a 35% increase in annual global healthcare expenditure related to diabetes, stemming from premature mortality, loss of productivity, or disability—generating 'indirect costs.' Since 1990, the cost of insulin globally has increased by over tenfold.
In mainland China, the estimated total number of diabetes patients exceeds 130 million, representing approximately one-third of the global population of diabetes patients. The overall healthcare expenditure for the treatment of diabetes and related conditions in China has surpassed 758.2 billion RMB annually, averaging nearly 6000 RMB per year per diabetes patient.
Whether it's type 1 or type 2 diabetes, both are chronic diseases that significantly impact people's health and quality of life. While existing treatment methods can to some extent control the condition, their therapeutic strategies still pose significant challenges to people's normal lives.
In recent decades, pancreatic transplantation has emerged as a potential treatment for type 1 diabetes. However, researchers have found that even in successful pancreatic transplants, the immune system may still reject the new pancreatic cells. On January 17, 2022, a research team from Northwestern University in the United States discovered that using a nano-carrier redesigned version of 'rapamycin' can make immune regulation more effective. However, the cost and risks associated with this treatment strategy remain high. Firstly, it requires a type 1 diabetes patient to find a pancreas organ that matches successfully. Secondly, it necessitates the use of quantified anti-rejection medications. Only under these conditions can the nano-carrier redesigned 'rapamycin' unleash its immune-regulating effects.
In other research directions, scientists are exploring the development of drugs targeting glucagon secretion to lower blood sugar levels in the body, with glucagon receptor GCGR as the target. Known DDP-4 inhibitors, GLP-1R agonists, GIP, starch mimetics, among others, can also inhibit glucagon secretion. Currently, drug development targeting glucagon inhibition primarily focuses on GLP-1R. GLP-1 is a gut hormone released by L cells after nutrient consumption. It is present in multiple areas such as pancreatic beta cells, heart, kidneys, lungs, gastrointestinal tract, central nervous system, and peripheral nerves [2-3]. It can induce pancreatic beta cells to secrete insulin, reduce glucagon secretion, and thereby regulate blood sugar levels. Approved drugs in this category include semaglutide, liraglutide, and exenatide.
In another research direction, scientists are attempting to treat diabetes by activating pancreatic beta cells, which is typically associated with immune responses and the adaptive immune system. Current research suggests that nanobodies may activate these cells by interacting with specific receptors or molecules on the surface of pancreatic beta cells. This interaction may trigger intracellular signal transduction pathways, activate the function of pancreatic beta cells, and restore cellular states. Alternatively, it may enhance insulin utilization by inhibiting the secretion of islet amyloid polypeptide (IAPP) while reducing its aggregation into amyloid fibrils deposited in the pancreas to prevent damage to alpha cells[4].
In conclusion, nanobodies have demonstrated immense potential in diabetes treatment research with their precise targeting capabilities, showcasing their versatility in modern medicine. They can deliver drugs to relevant pancreatic cells, stimulating or regulating their functions such as blood sugar-regulating proteins, insulin receptors, etc., thereby achieving precise therapeutic and monitoring functions through binding with drugs, imaging agents, or other therapeutic substances [5].
Traditional drug delivery methods have various limitations at different levels. It is worth considering whether redesigning nanobodies for drug delivery could enhance drug efficacy, reduce the frequency of drug administration, and mitigate drug toxicity. This approach holds promise and is currently garnering widespread attention and research globally in the development of nanobody-based drugs for diabetes treatment. As an innovative therapeutic modality, the complete treatment of diabetes using nanobody drugs in the future is a possibility worth exploring. The application prospects of nanobodies in this field are promising and may provide more effective and personalized treatment options for diabetic patients, further improving their quality of life.
As the Lunar New Year approaches, it is crucial to be mindful of the pancreatic damage caused by overeating. NBLST wishes all readers good health and a happy New Year!