Antioxidant drugs for treating beta-cell oxidative stress in type 2 diabetes: glucose-centric versus insulin-centric therapy.
Mainstays of therapy for type 2 diabetes involve drugs that are insulin-centric, i.e., they are designed to increase insulin secretion and decrease insulin resistance. The usual clinical course for people so treated is to have initially improved glycemic control but over time a need for intensification of drug-based treatment of hyperglycemia. The mechanism for this unrelenting deterioration of beta-cell function is related to chronic oxidative stress. This suggests that drug discovery should not exclusively focus on insulin-centric targets, but also include glucose-centric strategies, such as antioxidant protection of the beta-cell. This may facilitate repair of beta-cells undergoing damage by oxidative stress secondary to chronic hyperglycemia.
Robertson
R Paul
RP
Department of Medicine, University of Washington, 1959 N.E. Pacific Street, Seattle, Washington 98195, USA. rpr@pnri.org
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000628:therapy*; D005947:Glucose / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D013997:Time Factors
D000975:Antioxidants; D007328:Insulin; D005979:Glutathione Peroxidase; D005947:Glucose