Related Experiment Videos
Islet amyloid in type 2 (non-insulin-dependent) diabetes
A Clark1, S B Chargé, M K Badman
1Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK.
Summary
Islet amyloid polypeptide (IAPP) deposits contribute to type 2 diabetes by impairing beta cell function. Research suggests abnormal IAPP production and clearance accelerate amyloid fibril formation, worsening islet dysfunction.
Area of Science:
- Endocrinology
- Molecular Biology
- Diabetology
Background:
- Amyloid deposits in pancreatic islets are prevalent in type 2 diabetes.
- Islet amyloid is derived from islet amyloid polypeptide (IAPP), co-secreted with insulin by beta cells.
Purpose of the Study:
- To investigate the factors contributing to islet amyloid polypeptide (IAPP) fibrillogenesis.
- To understand the role of IAPP deposition in the pathogenesis of type 2 diabetes.
Main Methods:
- Analysis of IAPP sequence and production in relation to fibrillogenesis.
- Comparison of IAPP in human diabetic subjects and rodent models.
- In vitro culture of islets from transgenic mice expressing human IAPP.
Main Results:
- Rodent models lack islet amyloid due to proline substitutions in IAPP's amyloidogenic region.
- Human IAPP forms amyloid fibrils rapidly in cultured islets but not in vivo.
- Amyloid fibrils deposited between beta cells and capillaries may disrupt signaling and insulin release.
Conclusions:
- Abnormal IAPP production and impaired clearance are potential triggers for fibrillogenesis.
- Progressive IAPP deposition and beta cell loss likely contribute to declining islet function in type 2 diabetes.