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Chronic Exposure of Clonal Pancreatic β‐cells (INS‐1 832/13) to Pyruvate Inhibits Glucose‐induced Insulin Secretion
Author(s) -
Burritt Nathan Edward,
Corkey Barbara,
Deeney Jude T.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1010.11
Subject(s) - insulin , medicine , endocrinology , secretion , insulin resistance , extracellular , chemistry , biology , biochemistry
Objective Type 2 diabetes (T2D) occurs when pancreatic β‐cells fail to compensate for insulin resistance. Insulin resistance can be caused by a sustained elevation in insulin secretion, which may develop through a mechanism independent of the well‐established pathway described for fuel‐stimulated secretion. We hypothesize that nutrient availability can alter the redox state (NAD(P)H/NAD(P) ratio) leading to increases in reactive oxygen species (ROS) ultimately affecting insulin secretion.Methods To test this hypothesis we have incubated clonal pancreatic β‐cells (INS‐1 832/13) in increasing concentrations of Pyruvate (Pyr) (1–20 mM) or in varying ratios of Pyr and Lactate (Lac) for18–72 hrs in order to modify the REDOX capacity of the cell. Insulin secretion (HTRF), REDOX (autofluorescence), while insulin secretion and total insulin content where measured for Pyr and Lac. Results Pyr exposure decreased insulin secretion in a concentration dependent manner with a maximal inhibition of ~60% occurring at 5 mM. Conclusion Chronic exposure of INS‐1 cells to extracellular Pyr and Acoc inhibits insulin secretion by changing the REDOX state of the cells, affecting both insulin secretion and insulin content in a dose dependent manner.