Abstract
The deposition of aggregated human islet amyloid polypeptide (hIAPP) in the pancreas, that has been associated with β-cell dysfunction, is one of the common pathological features of patients with type 2 diabetes (T2D). Therefore, hIAPP aggregation inhibitors hold a promising therapeutic schedule for T2D. Chitosan oligosaccharides (COS) have been reported to exhibit a potential antidiabetic effect, but the function of COS on hIAPP amyloid formation remains elusive. Here, we show that COS inhibited the aggregation of hIAPP and disassembled preformed hIAPP fibrils in a dose-dependent manner by thioflavin T fluorescence assay, circular dichroism spectroscopy, and transmission electron microscope. Furthermore, COS protected mouse β-cells from cytotoxicity of amyloidogenic hIAPP, as well as apoptosis and cycle arrest. There was no direct binding of COS and hIAPP, as revealed by surface plasmon resonance analysis. In addition, both chitin-oligosaccharide and the acetylated monosaccharide of COS and glucosamine had no inhibition effect on hIAPP amyloid formation. It is presumed that, mechanistically, COS regulate hIAPP amyloid formation relating to the positive charge and degree of polymerization. These findings highlight the potential role of COS as inhibitors of hIAPP amyloid formation and provide a new insight into the mechanism of COS against diabetes.
Highlights
Type 2 diabetes (T2D), known as non-insulin-dependent diabetes, is a widespread chronic disease characterized by insulin resistance, progressive loss of pancreatic β-cell function and mass, impaired insulin release, and hyperglycemia [1,2]
Considering that T2D has comparable pathophysiological features with Alzheimer’s disease, we propose that the antidiabetic function of Chitosan oligosaccharides (COS) owns to the mechanism of anti-amyloid formation of Human islet amyloid polypeptide (hIAPP)
We provide the direct evidence that COS protect β-cells by alleviating the cytotoxicity of amyloidogenic hIAPP
Summary
Type 2 diabetes (T2D), known as non-insulin-dependent diabetes, is a widespread chronic disease characterized by insulin resistance, progressive loss of pancreatic β-cell function and mass, impaired insulin release, and hyperglycemia [1,2]. T2D is an age-related disease prevalent in adults over 40 years old, and accounts for 90–95% of the total number of diabetic patients [3]. A variety of factors, including glycolipid toxicity, inflammation, and cholesterol accumulation have been reported to correlate with β-cell dysfunction and occurrence of T2D [4]. It is suggested that the accumulation of aggregated islet amyloid polypeptides in the islets of Langerhans plays a critical role in pancreatic damage. Human islet amyloid polypeptide (hIAPP), alternate name amylin, is co-secreted with insulin by β-cells in the pancreas. It has been reported that aggregated hIAPP formed amyloid deposits in 70–90% of patients with T2D [5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
