Microarray analysis of somatostatin receptor 5-regulated gene expression profiles in murine pancreas.
BACKGROUND
We previously demonstrated that somatostatin receptor type 5 (SSTR5) gene ablation results in alterations in insulin secretion and glucose metabolism, accompanied by morphologic alterations in the islets of Langerhans. The underlying mechanism(s) by which SSTR5 exerts its cellular functions remain(s) unknown. We hypothesized that SSTR5 mediates the inhibitory effect of somatostatin (SST) on insulin secretion and islet proliferation by regulating a specific set of pancreatic genes.


METHODS
To identify SSTR5-regulated pancreatic genes, gene expression microarray analysis was performed on the whole pancreas of 1- and 3-month-old wild-type (WT) and SSTR5 knockout (SSTR5-/-) male mice. Real-time RT-PCR and immunofluorescence were performed to validate selected differentially expressed genes.


RESULTS
A set of 143 probes were identified to be differentially expressed in the pancreas of 1-month-old SSTR5-/- mice, 72 of which were downregulated and 71 upregulated. At 3 months of age, SSTR5 gene ablation resulted in downregulation of a set of 30 probes and upregulation of a set of 37 probes. Among these differentially expressed genes, there were 15 and 5 genes that were upregulated and downregulated, respectively, in mice at both 1 and 3 months of age. Three genes, PAP/INGAP, ANG, and TDE1, were selected to be validated by real-time RT-PCR and immunofluorescence.


CONCLUSIONS
A specific set of genes linked to a wide range of cellular functions such as islet proliferation, apoptosis, angiogenesis, and tumorigenesis were either upregulated or downregulated in SSTR5-deficient male mice compared with their expression in wild-type mice. Therefore, these genes are potential SSTR5-regulated genes during normal pancreatic development and functional maintenance.
Patel
Sanjeet G
SG
The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 1709 Dryden Street, Suite 1500, Houston, TX 77030, USA.
Zhou
Guisheng
G
Liu
Shi-He
SH
Li
Min
M
Jeong
Jae-Wook
JW
DeMayo
Francesco J
FJ
Gingras
Marie-Claude
MC
Gibbs
Richard A
RA
Fisher
William E
WE
Brunicardi
F Charles
FC
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D007515:Islets of Langerhans / Q000166:cytology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000196:embryology / Q000502:physiology; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic; D015854:Up-Regulation / Q000235:genetics; D008562:Membrane Glycoproteins
D009363:Neoplasm Proteins; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D017481:Receptors, Somatostatin; D012259:Ribonuclease, Pancreatic; C000612141:REG3A protein, human; C490253:Reg3b protein, mouse; C094573:somatostatin receptor 5; C046366:angiogenin; C470380:Serinc3 protein, mouse; D008562:Membrane Glycoproteins