Low doses of hydrogen peroxide impair glucose-stimulated insulin secretion via inhibition of glucose metabolism and intracellular calcium oscillations.
The inhibitory effect of hydrogen peroxide (H(2)O(2)) on glucose-stimulated insulin secretion was previously reported. However, the precise mechanism involved was not systematically investigated. In this study, the effects of low concentrations of H(2)O(2) (5-10 micromol/L) on glucose metabolism, intracellular calcium ([Ca(2+)](i)) oscillations, and dynamic insulin secretion in rat pancreatic islets were investigated. Low concentrations of H(2)O(2) impaired insulin secretion in the presence of high glucose levels (16.7 mmol/L). This phenomenon was observed already after 2 minutes of exposure to H(2)O(2). Glucose oxidation and the amplitude of [Ca(2+)](i) oscillations were dose-dependently suppressed by H(2)O(2). These findings indicate that low concentrations of H(2)O(2) reduce insulin secretion in the presence of high glucose levels via inhibition of glucose metabolism and consequent impairment in [Ca(2+)](i) handling.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP 05508-000, Brazil. rebelato@icb.usp.br
Eduardo
E
Rebelato
Fernando
F
Abdulkader
Rui
R
Curi
Angelo R
AR
Carpinelli
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats
D007202:Indicators and Reagents; D007328:Insulin; D016877:Oxidants; D006861:Hydrogen Peroxide; D005947:Glucose; D002118:Calcium