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The Effect C3a Will Have on Future Drug Development

Apr 13, 2021
 
Editor: Steve Freed, R.PH., CDE

Author: Sandra Zaki, PharmD Candidate, Florida A&M University

Researchers studying the effects of protein adispsin in type 2 diabetes find it activates a beta-cell protective peptide called C3a.

According to researchers, protein adipsin is produced in the body’s fat and has a prominent role in maintaining β cell function in patients with type 2 diabetes. Individuals that lack this protein may experience insulinopenia leading to the effect of glucose intolerance. By simply replenishing this protein, glucose levels can be lowered. More recently, the role of pancreatic beta-cell function and the impact beta-cell failure has on insulin production has been closely examined by researchers. It has been shown that some current therapies approved have been linked to rapid loss of beta cells. This study reveals that the protein adipsin can improve beta-cell insulin secretion and limit beta-cell death. This discovery demonstrates how helpful the protein can be in finding treatment for patients with type 2 diabetes.  

 

Cardiologist and assistant professor of medicine and pharmacology at Weill Cornell Medicine, Dr. James C. Lo, and colleagues set out to analyze the potential association between protein adipsin and type 2 diabetes. The study took placeat Harvard Medical School and Massachusetts General Hospital. The research team evaluated 5,570 subjects that were concurrently enrolled in the ongoing Framingham Heart Study, a cardiovascular investigation conducted in Massachusetts.   

Initially, the role of the adipokine adipsin in mice was being examined. In those studies, it was found that adipsin had a longstanding effect on diabetes in general. The protein sought to improve blood glucose levels and increase insulin levels, all while halting cell death. After investigating mice, the team decided to broaden their research. When exploring the relationship between protein adipsin and human beta cells, it was found that adipsin activated a peptide called C3a. Dr. Lo understood that the big issue related to diabetes is that beta cells stop functioning accordingly and dwindle, and C3a could assist with that issue. The molecule C3a protects and supports beta-cell function by disrupting death and damage to beta cells. This would make C3a a potent factor in the mechanism that creates the effects of adipsin. Later in the study, researchers identified that C3a suppresses DUSP26, an enzyme that diminishes beta cells’ health, ultimately resulting in cell death. Researchers dug deeper into the concept and discovered that suppressing DUSP26 activity creates healthier beta cells, subsequently leading to better insulin secretion.  

The examiners concluded that the possibility of developing type 2 diabetes was lower for individuals with elevated levels of adipsin in the blood when compared to individuals with the lowest levels of adipsin in the blood, especially in those individuals with increased levels that are associated with a fifty percent or more significant reduction in the incidence of diabetes. It was noted that collectively, the statistics propose that adipsin/C3a and DUSP26 directed therapies may very well be a unique means of arriving at the treatment of betacell health and preventing type 2 diabetes. In addition to the other findings, this study’s participants seemed to correlate the level of adipsin and the amount of subcutaneous fat.   

It is known that type 2 diabetes is correlated to insulin resistance and progressive loss of pancreatic beta-cell function and mass. With that awareness, researchers formed the theory that adipsin stimulation of beta cells resulting in insulin secretion might be a potential new therapy for patients with type 2 diabetes. In other words, manipulating the molecular pathway of adipsin/C3a may serve purpose in treating type 2 diabetes. The team made note that additional research would be imperative to determine the effects of increased adipsin, especially for future drug development.   

Practice Pearls: 

  • Protein adipsin can improve beta-cell insulin secretion and limit beta-cell death.  
  • C3a suppresses DUSP26, the enzyme that contributes to beta-cell death. 
  • Adipsin/C3a and DUSP26-directed therapies may very well be a unique means of arriving at the treatment of betacell health and the prevention of type 2 diabetes.  

 

Protective Protein Staves Off Diabetes. (2020). US Pharmacist. Retrieved from https://uspharmacist.com/article/protective-protein-staves-off-diabetes 

 

Sandra Zaki, PharmD Candidate, Florida A&M University