Regulation of integrin alpha 6A by lactogenic hormones in rat pancreatic beta-cells: Implications for the physiological adaptation to pregnancy
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- Regulation of integrin alpha 6A by lactogenic hormones in rat pancreatic beta-cells_Implications for the physiological adaptation to pregnancy_(accepted_version)
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Aim During pregnancy, the maternal beta-cell mass is increased in order to adapt to the physiological changes in insulin demand. Lactogenic hormones stimulate rodent beta-cell attachment and proliferation in vitro. The aim of this study was to identify adhesion molecules involved in expansion of the beta-cell mass during pregnancy in the rat.
Methods Quantitative RT-PCR was used to evaluate the expression of several integrins and laminins in isolated neonatal rat islets in response to growth hormone (GH) and prolactin (PRL) treatment. Double-immunofluorescence staining of rat pancreas was used to localize the expression of integrin alpha 6 beta 1. beta-cell proliferation was evaluated by incorporation of bromodeoxyuridine (BrdU). The role of STAT5 phosphorylation was tested by addition of STAT5 mutants.
Results We found that the mRNA level of integrin-alpha 6A, was upregulated 2.5-fold by PRL or GH. During pregnancy, a biphasic 3.4-4.5-fold increase of integrin-alpha 6A and B mRNA levels was detected. A disintegrin peptide (DP) reduced the hormone-stimulated mitotic activity in neonatal rat beta-cells from 2.9 +/- 0.4-fold to 1.3 +/- 0.3-fold. The hormone-induced expression of alpha 6 beta 1 integrin was shown to be mediated via STAT5 as a dominant negative (DN) mutant prevented and a constitutive active (CA) mutant augmented the hGH-stimulated expression. The DP was found to inhibit hGH-induced transactivation of the PRL receptor promoter 1A and reduce the hGH-induced phosphorylation of STAT5.
Conclusion These results show that integrin-alpha 6 in beta-cells is upregulated by lactogenic hormones and is required but not sufficient for the expansion of the beta-cell mass in pregnancy in the rat, which may have implications for the understanding and treatment of gestational diabetes mellitus.
|Udgivet - 2020