Amyloid damage to islet β-cells in type 2 diabetes: hypoxia or pseudo-hypoxia?

Abstract

Aggregation of islet amyloid polypeptide (IAPP) and amyloid deposition in the islets ofLangerhans may significantly contribute to the multifactorial pathogenic mechanisms leading to type 2 diabetes. A direct toxic effect on β-cells of oligomeric IAAP has been demonstrated in in vitro models, but the mechanism operating in vivo is still unclear.Mice models presenting amyloid deposition and glucose intolerance represent a good tool for exploring in vivo a putative mechanism of toxicity directly related to the physical expansion of the extracellular matrix by the amyloid fibrillar aggregates.Based on our hypothesis that deposition of amyloid may influence the oxygen perfusion, we have calculated that the mean distribution of oxygen partial pressure would drop by more than 50 % in the presence of amyloid deposits in the islet. This condition of hypoxia caused by the remodelling of the extracellular space may explain the metabolic abnormalities in the Langerhans islets, otherwise interpreted as pseudo-hypoxic response to IAPP oligomers.

The Potential of Albuminuria as a Biomarker of Diabetic Complications

“…Lack of glucose utilisation by adipose tissue promotes free fatty acid production which has been shown to induce programmed cell death of β-cells [30,31]. Recently, the role of islet amyloid protein in β-cell death has been described [32,33]. This polypeptide is released along with insulin in response to increased blood sugar levels.…”