Islet redox stress: the manifold toxicities of insulin resistance, metabolic syndrome and amylin derived islet amyloid in type 2 diabetes mellitus

Abstract

Context: Redox stress, reactive oxygen species, reactive nitrogen species, and oxygen free radicals ("toxic oxygen") are increasingly being reported as important cellular signaling mechanisms. It has been known for over a hundred years that type 2 diabetes mellitus is a manifold disease, not only in its etiology, but also in its associated manifold toxicities and multiple complications of the diabetic opathies. The presence of islet amyloid has also been described in association with type 2 diabetes mellitus for a century.

Objective: This review will attempt to remain focused on the relationship between redox stress, the reactive oxygen species and the reactive nitrogen species in the islet, and how these interact with the multiplicative effect of the toxicities of insulin resistance, metabolic syndrome, amylin (hyperamylinemia), amylin derived islet amyloid and type 2 diabetes mellitus.

Conclusions: Redox sensitive cellular signaling systems play an important role in the development, progressive nature (remodeling) and damaging effects on the beta cell within the islet of the pancreas. Furthermore, redox stress may play an important role in the remodeling and development of islet amyloid creating a space-occupying lesion with a resultant secretory and absorptive defect within the islet. The presence of manifold toxicities necessitates an approach of global risk reduction in the prevention and treatment of type 2 diabetes mellitus. An improved understanding of the dynamic relationship between these toxicities and redox stress within the islet will aid both the researcher and the clinician.