Regulation of Integrin α6A by Lactogenic Hormones in Rat Pancreatic β-Cells: Implications for the Physiological Adaptation to Pregnancy

Annette Møldrup, Martin Nerup Lindberg, Elisabeth D. Galsgaard, Ulrik Henriksen, Louise Torp Dalgaard, Jens H. Nielsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

Aim: During pregnancy the maternal β-cell mass is increased in order to adapt to the physiological changes in insulin demand. Lactogenic hormones stimulate rodent β-cell attachment and proliferation in vitro. The aim of the study was to identify adhesion molecules involved in expansion of the β-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 and prolactin treatment. Double-immunofluorescence staining of rat pancreas was used to localize the expression of integrin α6β1. β-cell proliferation was evaluated by incorporation of bromodeoxyuridine. The role of STAT5 phosphorylation was tested by addition of STAT5 mutants. Results: We found that the mRNA level of integrin-α6A, was upregulated 2.5-fold by prolactin or growth hormone. During pregnancy a bi-phasic 3.4-4.5-fold increase of integrin-α6A and B mRNA levels was detected. A disintegrin peptide reduced the hormone-stimulated mitotic activity in neonatal rat β-cells from 2.9 ± 0.4-fold to 1.3 ± 0.3-fold. The hormone-induced expression of α6β1 integrin was shown to be mediated via STAT5 as a dominant negative mutant prevented and a constitutive active mutant augmented the hGH stimulated expression. The disintegrin peptide 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-α6 in β-cells is upregulated by lactogenic hormones and is required but not sufficient for the expansion of the β-cell mass in pregnancy in the rat, which may have implications for the understanding and treatment of gestational diabetes.
OriginalsprogEngelsk
Artikelnummere13454
TidsskriftActa Physiologica
ISSN1748-1708
DOI
StatusUdgivet - 2020

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