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.
Møldrup, A., Lindberg, M. N., Galsgaard, E. D., Henriksen, U., Dalgaard, L. T., & Nielsen, J. H. (2020). Regulation of Integrin α6A by Lactogenic Hormones in Rat Pancreatic β-Cells: Implications for the Physiological Adaptation to Pregnancy. Acta Physiologica, [e13454]. https://doi.org/10.1111/apha.13454