AI Article Synopsis
- Patients with type 2 diabetes experience a decline in pancreatic beta cell function, leading to insulin production issues and blood glucose regulation problems.
- The deterioration of these cells is linked to the buildup of toxic forms of islet amyloid polypeptide (IAPP), including both soluble and insoluble aggregates.
- A newly developed human monoclonal antibody targets the harmful IAPP oligomers, demonstrating protective effects on beta cells and improved glucose control in animal models, indicating a potential therapeutic approach for enhancing beta cell function in type 2 diabetes.
Article Abstract
In patients with type 2 diabetes, pancreatic beta cells progressively degenerate and gradually lose their ability to produce insulin and regulate blood glucose. Beta cell dysfunction and loss is associated with an accumulation of aggregated forms of islet amyloid polypeptide (IAPP) consisting of soluble prefibrillar IAPP oligomers as well as insoluble IAPP fibrils in pancreatic islets. Here, we describe a human monoclonal antibody selectively targeting IAPP oligomers and neutralizing IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro. Antibody treatment in male rats and mice transgenic for human IAPP, and human islet-engrafted mouse models of type 2 diabetes triggers clearance of IAPP oligomers resulting in beta cell protection and improved glucose control. These results provide new evidence for the pathological role of IAPP oligomers and suggest that antibody-mediated removal of IAPP oligomers could be a pharmaceutical strategy to support beta cell function in type 2 diabetes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562398 | PMC |
| http://dx.doi.org/10.1038/s41467-023-41986-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!