AAV8-mediated gene transfer of microRNA-132 improves beta cell function in mice fed a high-fat diet

Niels L. Mulder, Rick Havinga, Joost Kluiver, Albert K. Groen, Janine K. Kruit*

*Corresponding author voor dit werk

    OnderzoeksoutputAcademicpeer review

    14 Citaten (Scopus)
    154 Downloads (Pure)

    Samenvatting

    MicroRNAs have emerged as essential regulators of beta cell function and beta cell proliferation. One of these microRNAs, miR-132, is highly induced in several obesity models and increased expression of miR-132 in vitro modulates glucose-stimulated insulin secretion. The aim of this study was to investigate the therapeutic benefits of miR-132 overexpression on beta cell function in vivo. To overexpress miR-132 specifically in beta cells, we employed adeno-associated virus (AAV8)-mediated gene transfer using the rat insulin promoter in a double-stranded, self-complementary AAV vector to overexpress miR-132. Treatment of mice with dsAAV8-RIP-mir132 increased miR-132 expression in beta cells without impacting expression of miR-212 or miR-375. Surprisingly, overexpression of miR-132 did not impact glucose homeostasis in chow-fed animals. Overexpression of miR-132 did improve insulin secretion and hence glucose homeostasis in high-fat diet-fed mice. Furthermore, miR-132 overexpression increased beta cell proliferation in mice fed a high-fat diet. In conclusion, our data show that AAV8-mediated gene transfer of miR-132 to beta cells improves beta cell function in mice in response to a high-fat diet. This suggests that increased miR-132 expression is beneficial for beta cell function during hyperglycemia and obesity.

    Originele taal-2English
    Pagina's (van-tot)123-132
    Aantal pagina's10
    TijdschriftJournal of endocrinology
    Volume240
    Nummer van het tijdschrift2
    DOI's
    StatusPublished - feb.-2019

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