1. Regulation of integrin α6A by lactogenic hormones in rat pancreatic β‐cells: Implications for the physiological adaptation to pregnancy
- Author
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Jens Høiriis Nielsen, Ulrik L. Henriksen, Elisabeth D. Galsgaard, Martin N. Lindberg, Louise Torp Dalgaard, and Annette Møldrup
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Physiology ,Integrin ,Integrin alpha6 ,030204 cardiovascular system & hematology ,INSULIN-SECRETION ,GLYCOGEN-SYNTHASE KINASE ,Islets of Langerhans ,03 medical and health sciences ,Transactivation ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,Pregnancy ,Insulin-Secreting Cells ,Internal medicine ,EXTRACELLULAR-MATRIX ,medicine ,Animals ,Receptor ,MOLECULAR-CLONING ,biology ,Chemistry ,lactogenic hormones ,GESTATIONAL DIABETES-MELLITUS ,PROTEIN-KINASE ,PROLACTIN RECEPTOR ,Adaptation, Physiological ,ENDOCRINE PANCREAS ,Prolactin ,Rats ,Signal Transducer and Activator of Transcription 5 (STAT5) ,030104 developmental biology ,Endocrinology ,Growth Hormone ,integrins ,beta-cells ,biology.protein ,Female ,SIGNAL TRANSDUCER ,pregnancy ,islets of Langerhans ,GROWTH-HORMONE ,ITGA6 ,Bromodeoxyuridine ,Hormone - Abstract
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.
- Published
- 2020
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