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Effects of islet neogenesis-associated protein pentadecapeptide on cell mass and insulin secretion of pancreatic β-cells

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Abstract

Objective: To explore the effects of islet neogenesis-associated protein pentadecapeptide (INGAP-PP) on proliferation and secretion function of β-cells. Methods: Islets of adult Sprague Dawley rats were isolated by colla-genase digestion and treated with 10 µg/ml INGAP-PP, after 12, 24, 48 h, glucose-stimulated insulin secretion (GSIS) and acridine orange/propidium iodide (AO/PI) staining were used to detect the secretion function and cell viability. The INS-1 cells were treated with 0, 1, 10, 25, 50, 100, 250, and 500 µg/ml INGAP-PP for 24 or 48 h, MTT cell proliferation assay was adopted to survey the dose-response relationship between INGAP-PP and cell proliferation. The mRNA expression of roliferating cell nuclear antigen (PCNA), Cyclin D1, Cdk4, P27, p38MAPK, and JNK in INS-1 cells were examined by RT-PCR, and the protein expression of PCNA was examined by Western blot. The statistical significance was determined by Student’s t-test or one-way analysis of variance. Results: The insulin secreted by islets and the cell viability were increased by INGAP-PP. MTT indicated a dose-response relationship between INGAP-PP and quantity of INS-1 cells, and treatment for 48 h had a stronger effect on cell proliferation than the 24 h. INGAP-PP up-regulated the mRNA expression of PCNA, Cyclin D1, Cdk4 and down-regulated P27, p38MAPK, and JNK. Moreover, the protein expression of PCNA was up-regulated by 45% after INGAP-PP exposure for 48 h. Conclusions: INGAP-PP increased the insulin secretion, enhanced the proliferation and might reduce apoptosis of β-cells. The mechanism may contribute to the changed expression of some genes related to cell cycle.

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Authors and Affiliations

  1. Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China

    M. Zha, M. Zhang, S. Shan, K.-F. Xu, H. Chen, X.-Y. Xu, L. Qian & T. Yang

  2. Key Laboratory of Human Functional Genomics of Jiangsu Province, Clinical Diabetes Centre of Jiangsu Province, Nanjing Medical University, Nanjing, China

    X. Han

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  1. M. Zha
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  2. M. Zhang
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  3. S. Shan
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  4. K.-F. Xu
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  5. H. Chen
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  6. X.-Y. Xu
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  7. L. Qian
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  9. T. Yang
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Correspondence to T. Yang.

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Zha, M., Zhang, M., Shan, S. et al. Effects of islet neogenesis-associated protein pentadecapeptide on cell mass and insulin secretion of pancreatic β-cells. J Endocrinol Invest 35, 634–639 (2012). https://doi.org/10.3275/7922

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  • DOI: https://doi.org/10.3275/7922

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