Regulation of pancreatic islet gene expression in mouse islets by pregnancy.
Pancreatic β cells adapt to pregnancy-induced insulin resistance by unclear mechanisms. This study sought to identify genes involved in β cell adaptation during pregnancy. To examine changes in global RNA expression during pregnancy, murine islets were isolated at a time point of increased β cell proliferation (E13.5), and RNA levels were determined by two different assays (global gene expression array and G-protein-coupled receptor (GPCR) array). Follow-up studies confirmed the findings for select genes. Differential expression of 110 genes was identified and follow-up studies confirmed the changes in select genes at both the RNA and protein level. Surfactant protein D (SP-D) mRNA and protein levels exhibited large increases, which were confirmed in murine islets. Cytokine-induced expression of SP-D in islets was also demonstrated, suggesting a possible role as an anti-inflammatory molecule. Complementing these studies, an expression array was performed to define pregnancy-induced changes in expression of GPCRs that are known to impact islet cell function and proliferation. This assay, the results of which were confirmed using real-time reverse transcription-PCR assays, demonstrated that free fatty acid receptor 2 and cholecystokinin receptor A mRNA levels were increased at E13.5. This study has identified multiple novel targets that may be important for the adaptation of islets to pregnancy.
Layden
B T
BT
Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Tarry 15, Chicago, Illinois 60611, USA.
Durai
V
V
Newman
M V
MV
Marinelarena
A M
AM
Ahn
C W
CW
Feng
G
G
Lin
S
S
Zhang
X
X
Kaufman
D B
DB
Jafari
N
N
Sørensen
G L
GL
Lowe
W L
WL
D000818:Animals; D016207:Cytokines / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D011247:Pregnancy; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D043886:Receptor, Cholecystokinin A / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics
D016207:Cytokines; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C506481:Ffar2 protein, mouse