Islet amyloid polypeptide: actions and role in the pathogenesis of diabetes

Abstract

IAPP has been postulated to have a role as a modulating factor in glucose homoeostasis and to be involved in the pathophysiology of diabetes. However, the normal physiological functions of the peptide remain obscure: exogenous IAPP acts on many experimental systems to modulate nutrient supply and metabolism but there is no evidence to suggest that circulating IAPP has an aetiological role in the onset of Type-2 diabetes. Amyloid deposits formed from polymerized IAPP progressively accumulate in the islets of Type-2 diabetic patients. These insoluble deposits do not precipitate the onset of hyperglycaemia in Type-2 diabetes, but progressive accumulation of amyloid is associated with islet cell destruction and decreased islet function in the later stages of the disease. Although the causative factors of formation of the first IAPP fibril are unknown, continued high levels of insulin and IAPP secretion as a result of nutrient stimulation or insulin resistance will promote binding to preformed fibrils and extension of the deposits. It is important that methods to identify patients susceptible to amyloid deposition are developed and therapeutic agents are produced that can reduce or prevent polymerizatin of IAPP to form amyloid and minimize severe deterioration of islet function in Type-2 diabetes.

Protective effects of cyanidin-3-rutinoside against monosaccharides-induced protein glycation and oxidation

“…The accumulations of ␤-amyloid cross structure in specific organs or tissues may contribute to amyloidosis which plays a role in the pathological progression. For instance, the islet amyloid polypeptide deteriorated the islet function in type 2 diabetes [41]. Moreover, the accumulation of amyloid plaques represents a major breakthrough in neurodegenerative diseases [42].…”

Inhibition of BACE2 counteracts hIAPP‐induced insulin secretory defects in pancreatic β‐cells

“…It is well known that the progressive loss of β‐cell mass and function are key features of the manifestation of the underlying disease (1). One of the main factors involved in the process of pancreatic β‐cell deterioration is the accumulation of pancreatic amyloid deposits (2), which are considered a hallmark of T2D (3, 4). Because islet amyloid deposits colocalize with areas of β‐cell degeneration, the process of amyloidosis has been strongly associated with a progressive loss of pancreatic β‐cell mass and therefore with the pathology of T2D (5).…”

Aberrant Processing of Human Proislet Amyloid Polypeptide Results in Increased Amyloid Formation

“…The amount of amyloid deposited varies, but it is present to some degree in 40 -95% of the patients (1)(2)(3), and a decrease in the number of ␤-cells follows the accumulation of islet amyloid (4 -6). The main amyloid constituent is the 37-amino acid polypeptide hormone islet amyloid polypeptide (IAPP) (7) or amylin (8).…”