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*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-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.
Original languageEnglish
Article numbere13454
JournalActa Physiologica
Volume229
Issue number3
ISSN1748-1708
DOIs
Publication statusPublished - 2020

Bibliographical note

Important note from the Publisher regarding the attached version of the article: "This is the peer reviewed version of the following article: Møldrup, A, Lindberg, MN, Galsgaard, ED, Henriksen, U, Dalgaard, LT, Nielsen, JH. Regulation of integrin α6A by lactogenic hormones in rat pancreatic β‐cells: Implications for the physiological adaptation to pregnancy. Acta Physiol. 2020; 229:e13454. , which has been published in final form at https://doi.org/10.1111/apha.13454. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."

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