Proteomics

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Quantitative proteomics of intestinal mucosa from male mice lacking intestinal epithelial insulin receptors


ABSTRACT: The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was deployed on jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon. There was also a significant effect of the WD on the gut proteome. A significant reduction was detected in Paneth cell proteins with anti-microbial activity, including lysozyme C-1, angiogenin-4, cryptdin-related sequence1C-3 and -2, a-defensin 17 and intelectin-1a. The key protein expressed by goblet cells, mucin-2, was also reduced in the IE-irKO mice. Proteins involved in lipid metabolism, including aldose reductase-related protein 1, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], apolipoprotein A-II and pyruvate dehydrogenase kinase isozyme 4, were increased in the mucosa of WD-fed IE-irKO mice as compared to controls. In contrast, expression of the nutrient-responsive gut hormones, glucose-dependent insulinotropic polypeptide and neurotensin, was reduced in the jejunal mucosa of IE-irKO mice, and there was a reduction in proteins of the P-type ATPases and the solute carrier-transporter family in the colon of WD-fed IE-irKO mice. In conclusion, IE-irKO mice display a distinct molecular phenotype, suggesting a biological role of insulin and its receptor in determining differentiated cell-specificity in the intestinal epithelium.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Colon

SUBMITTER: Erwin Schoof  

LAB HEAD: Patricia L. Brubaker

PROVIDER: PXD005932 | Pride | 2017-08-18

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20150804_HF_ES_SIRJ_TMT_MS1_1_I.raw Raw
20150804_HF_ES_SIRJ_TMT_MS1_2_I.raw Raw
20150804_HF_ES_SIRJ_TMT_MS1_3_I.raw Raw
20150804_HF_ES_SIRJ_TMT_MS1_4_I.raw Raw
20150804_HF_ES_SIRJ_TMT_MS1_5_I.raw Raw
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Publications

Quantitative Proteomics of Intestinal Mucosa From Male Mice Lacking Intestinal Epithelial Insulin Receptors.

Jensen Stina Rikke SR   Schoof Erwin M EM   Wheeler Sarah E SE   Hvid Henning H   Ahnfelt-Rønne Jonas J   Hansen Bo Falck BF   Nishimura Erica E   Olsen Grith Skytte GS   Kislinger Thomas T   Brubaker Patricia L PL  

Endocrinology 20170801 8


The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by liquid chromatography mass spectrometry was applied to jejunal and colonic mucosa from mice fed a normal chow diet and mice fed a Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterati  ...[more]

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