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The aim of this study was to investigate the regulating effect of pericentrin (PCNT) on insulin secretion in the development of insulin resistance and to determine the underlying mechanism. PCNT expression was studied in different tissues of C57/B6 mice by reverse transcriptase-PCR and immunofluorescence. PCNT was highly expressed in organs involved in the regulation of metabolism, while cytoplasmic expression was only enriched in islet cells. PCNT expression was significantly lower in the central regions of insulin resistance (IR) mouse islets than in those of control mouse islets. PCNT expression was further studied in mouse MIN6 cells exposed to glucose stimulation, small interfering RNA (siRNA) against PCNT, and an ERK inhibitor (PD98095). The results revealed that PCNT expression in glucose-stimulated MIN6 cells reduced linearly with cytoplasmic insulin levels. MIN6 cells transfected with PCNT siRNA showed significantly decreased intracellular insulin and F-actin expression. The change in F-actin expression in MIN6 cells during PCNT siRNA interference showed a linear relationship with PCNT expression at different time points. The ERK inhibitor affected PCNT expression and F-actin expression linearly. The abnormal insulin secretion observed both in vivo and in vitro was associated with decreased PCNT expression, and F-actin was found to be the target of PCNT regulation. [ABSTRACT FROM AUTHOR]