Dataset Information

Phosphoproteome of mouse pancreatic beta cell

ABSTRACT: TMT-labeled phosphoproteome data of mouse pancreatic beta cell

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Yoshiko Matsumoto Ikushima

PROVIDER: PXD022745 | JPOST Repository | Tue May 11 00:00:00 BST 2021

REPOSITORIES: jPOST

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			Action	DRS
	191016_Ikushima_TMT_set1_fr1.raw	Raw
	191016_Ikushima_TMT_set1_fr2.raw	Raw
	191016_Ikushima_TMT_set1_fr3.raw	Raw
	191016_Ikushima_TMT_set1_fr4.raw	Raw
	191016_Ikushima_TMT_set1_fr5.raw	Raw

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Publications

MEK/ERK Signaling in β-Cells Bifunctionally Regulates β-Cell Mass and Glucose-Stimulated Insulin Secretion Response to Maintain Glucose Homeostasis.

Ikushima Yoshiko Matsumoto YM Awazawa Motoharu M Kobayashi Naoki N Osonoi Sho S Takemiya Seiichi S Kobayashi Hiroshi H Suwanai Hirotsugu H Morimoto Yuichi Y Soeda Kotaro K Adachi Jun J Muratani Masafumi M Charron Jean J Mizukami Hiroki H Takahashi Noriko N Ueki Kohjiro K

Diabetes 20210427 7

In diabetic pathology, insufficiency in β-cell mass, unable to meet peripheral insulin demand, and functional defects of individual β-cells in production of insulin are often concurrently observed, collectively causing hyperglycemia. Here we show that the phosphorylation of ERK1/2 is significantly decreased in the islets of <i>db/db</i> mice as well as in those of a cohort of subjects with type 2 diabetes. In mice with abrogation of ERK signaling in pancreatic β-cells through deletion of <i>Mek1 ...[more]

PMID: 33906910

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Project description:Pancreatic β-cells have the key homeostatic function of releasing insulin to keep blood glucose in the normal range. It is not fully understood how β-cell mass is determined. Ablation of a nuclear receptor, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), in mouse pancreatic β-cells results in glucose intolerance and 50% fewer β-cells during the postnatal period. By testing islets isolated from these mice and cultured β-cells with loss and gain of COUP-TFII function, we found that COUP-TFII induces β-catenin thus upregulating target genes like cyclin D1. Beta-cell expansion triggered by glucagon-like peptide 1 (GLP-1) is known to be mediated by β-catenin controlling cyclin D1. We show that in the absence of COUP-TFII, exendin-4, an agonist of the GLP-1 receptor, does not fully induce cyclin D1 expression, while overexpression of β-catenin induces cyclin D1. A marked decrease in cyclin D1 expression is detected in islets isolated from transgenic mice lacking both GLP-1 receptor and gastric inhibitory peptide receptor. COUP-TFII is therefore required for GLP-1 activation of the β-catenin-dependent pathway in pancreatic β-cells to increase β-cell number. To understand the molecular mechanisms by which COUP-TFII controls β-cell mass, we determined the RNA profile of COUP-TFII knockdown β-cells using Affymetrix oligonucleotide microarrays. Computational analysis identified clusters of genes shared by different gene regulatory Networks that are up or down regulated namely genes involved in Wnt/β-catenin signaling, insulin signaling and lipid/carbohydrate metabolism. We determined the RNA profile of COUP-TFII knockdown β-cells (832/13 INS-1 cells transfected with COUP-TFII specific siRNA) with respect to control cells (832/13 INS-1 cells transfected with scrambled siRNA) using Affymetrix expression analysis technical manual 701025Rev.5 (Affymetrix, Santa Clara, California, USA). Briefly, 1 mg of total cellular mRNA was reverse transcribed into cDNA (SuperScript Choice System Invitrogen, Carlsbad, CA) using oligo-dT primers and a T7 RNA polymerase promoter site. The cDNA was in vitro transcribed and biotin-labeled for microarray analysis using the Affymetrix IVT labeling kit. The concentration of labelled cRNA was measured using a NanoDrop ND-1000 spectrophotometer. Labeled cRNA was fragmented in a fragmentation buffer for 35 min at 94°C. The quality of labeled and fragmented cRNA was analyzed using the Agilent bioanalyzer 2100 (Van Lommel et al, 2006). Fragmented cRNA was hybridized to the rat 230 2.0 array (Affymetrix) during 16h at 45°C. Arrays were washed and stained in a fluidics station (Affymetrix) and scanned using the Affymetrix 3000 GeneScanner.