Adrenomedullin and its receptors are expressed in mouse pancreatic β-cells and suppresses insulin synthesis and secretion.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2022
2022
Historique:
received:
13
01
2022
accepted:
09
03
2022
entrez:
24
3
2022
pubmed:
25
3
2022
medline:
6
5
2022
Statut:
epublish
Résumé
Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, RAMPs are present in mouse pancreatic islets and co-localized with insulin. The expressions of ADM, CRLR and RAMP2 in islets from pregnant mice are reduced compared to that of non-pregnant mice. NIT-1-β cells express ADM and its receptor mRNA, and glucose dose-dependently stimulates expressions. Furthermore, ADM inhibits NIT-1-β cell growth, and this inhibition is reversed by ADM antagonist, ADM22-52. The glucose-induced insulin secretion was suppressed by ADM in NIT-1-β cells and isolated pancreatic islets from pregnant mice. These inhibitory effects are accompanied by upregulation of endoplasmic reticulum (ER) stress biomarker genes in NIT-1-β cells. This study unveils that reduced ADM and its receptors may play a role in β-cell adaptation during pregnancy, while increased plasma ADM in GDM may contribute to the β-cells dysfunction, and blockade of ADM may reverse β-cell insulin production.
Identifiants
pubmed: 35324977
doi: 10.1371/journal.pone.0265890
pii: PONE-D-22-01233
pmc: PMC8947024
doi:
Substances chimiques
Insulin
0
Insulin, Regular, Human
0
Receptors, Adrenomedullin
0
Adrenomedullin
148498-78-6
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0265890Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL058144
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Peptides. 1999 Dec;20(12):1471-8
pubmed: 10698123
Biochem Biophys Res Commun. 1993 Apr 30;192(2):553-60
pubmed: 8387282
Biol Reprod. 2017 Feb 1;96(2):435-445
pubmed: 28203773
Annu Rev Biochem. 2005;74:739-89
pubmed: 15952902
J Biol Chem. 2003 Aug 29;278(35):32969-77
pubmed: 12810726
Diabetes. 2002 Feb;51 Suppl 1:S37-42
pubmed: 11815456
Biol Reprod. 2002 Sep;67(3):1025-31
pubmed: 12193417
J Proteome Res. 2009 Jun;8(6):2851-62
pubmed: 19351151
Am J Obstet Gynecol. 1975 Aug 1;122(7):829-33
pubmed: 1146934
Diabetologia. 2007 Apr;50(4):752-63
pubmed: 17268797
J Clin Endocrinol Metab. 2017 Sep 1;102(9):3425-3436
pubmed: 28666334
Trends Endocrinol Metab. 2012 Jun;23(6):278-85
pubmed: 22537825
Endocrinology. 2000 Jan;141(1):406-11
pubmed: 10614663
J Biol Chem. 2007 Nov 2;282(44):32084-92
pubmed: 17761679
Nature. 1998 May 28;393(6683):333-9
pubmed: 9620797
Endocrinology. 1996 Jun;137(6):2626-32
pubmed: 8641217
Endocrinology. 1998 Aug;139(8):3432-41
pubmed: 9681493
Hypertens Res. 2002 Nov;25(6):887-92
pubmed: 12484513
Cell Tissue Res. 1998 Jul;293(1):95-100
pubmed: 9634601
Diabetes. 2000 Dec;49(12):2208-11
pubmed: 11118027
Diabetes Metab. 2014 Nov;40(5):323-30
pubmed: 24948417
Am J Physiol Endocrinol Metab. 2006 Jul;291(1):E9-E14
pubmed: 16760337
Nat Rev Endocrinol. 2014 Mar;10(3):129-30
pubmed: 24393784
J Clin Invest. 2002 Feb;109(4):525-32
pubmed: 11854325
Curr Vasc Pharmacol. 2013 Sep;11(5):641-54
pubmed: 24063381
Biol Reprod. 2015 Dec;93(6):134
pubmed: 26510864
Diabetes. 1991 Jan;40(1):1-6
pubmed: 1901807
Nat Cell Biol. 2000 Jun;2(6):326-32
pubmed: 10854322
J Clin Endocrinol Metab. 2019 Mar 1;104(3):697-706
pubmed: 30383252
Endocrinology. 2012 Sep;153(9):4556-67
pubmed: 22778222
J Vis Exp. 2014 Jun 25;(88):e50374
pubmed: 24998772
Endocrinology. 2016 Jul;157(7):2636-48
pubmed: 27145007
Lancet. 1997 Nov 15;350(9089):1449-50
pubmed: 9371176
Gen Comp Endocrinol. 1999 Sep;115(3):309-22
pubmed: 10480982
Microsc Res Tech. 2002 Apr 1;57(1):28-39
pubmed: 11921354
Apoptosis. 2002 Aug;7(4):335-45
pubmed: 12101393
Endocr Rev. 2008 May;29(3):317-33
pubmed: 18436705
Regul Pept. 1996 Apr 23;62(2-3):107-12
pubmed: 8795072
Regul Pept. 2003 Apr 15;112(1-3):121-30
pubmed: 12667633
Acta Obstet Gynecol Scand. 2008;87(12):1266-70
pubmed: 18846453
Peptides. 1997;18(7):1079-89
pubmed: 9357070
Diabetes Care. 2007 Jul;30 Suppl 2:S141-6
pubmed: 17596462
Endocrinology. 1992 Mar;130(3):1459-66
pubmed: 1537300