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| Status |
Public on Mar 21, 2019 |
| Title |
Toll-like receptors 2 and 4 control adaptive β-cell expansion in diet-induced obesity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Adult pancreatic β cells are refractory to proliferation, a roadblock for the treatment of insulin-deficient diabetes. Consumption of energy-dense Western or high-fat diet (HFD) triggers mild adaptive β cell mass expansion to compensate for peripheral insulin resistance; however, the underlying molecular mechanism remains unclear. Here we show that Toll-like receptors (TLR) 2/TLR4 act as molecular “brakes” for diet-induced β cell replication in both mice and humans. The combined loss of TLR2/TLR4, but not individually, dramatically increases facultative β, not α, cell replication, leading to progressively enlarged islet mass and hyperinsulinemia in diet-induced obesity. Mechanistically, loss of TLR2/TLR4 increases β cell proliferation and nuclear abundance of Cyclin D2 and CDK4 in an extracellular signal-regulated kinase (ERK)-dependent manner. These data reveal a novel mechanism governing adaptive β cell mass expansion in diet-induced obesity and suggest that selective targeting of TLR2/TLR4 pathways may hold promise for reversing β cell failure in diabetic patients.
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| Overall design |
Pancreatic islets were isolated from wild type and Tlr2/Tlr4 double knockout mice after high-fat diet intervention for 5 wks or 7 months and subjected to genome wide expression profiling.
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| Contributor(s) |
Ji Y, Shengyi S, Shrestha N, Darragh L, Shirakawa J, Xing Y, He Y, Carboneau B, Kim G, Kim H, Xin S, An D, Ma M, Oberhozler J, Soleimanpour S, Gannon M, Liu C, Naji A, Kulkarni R, Wang Y, Kersten S, Qi L |
| Citation(s) |
31110312 |
| Submission date |
Jul 13, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (14)
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| GSM2701883 |
pancreatic islets, wild type, 5 wks HFD intervention, replicate 1 |
| GSM2701884 |
pancreatic islets, wild type, 5 wks HFD intervention, replicate 2 |
| GSM2701885 |
pancreatic islets, wild type, 5 wks HFD intervention, replicate 3 |
| GSM2701886 |
pancreatic islets, wild type, 5 wks HFD intervention, replicate 4 |
| GSM2701887 |
pancreatic islets, Tlr2/Tlr4 DKO, 5 wks HFD intervention, replicate 1 |
| GSM2701888 |
pancreatic islets, Tlr2/Tlr4 DKO, 5 wks HFD intervention, replicate 2 |
| GSM2701889 |
pancreatic islets, wild type, 7 months HFD intervention, replicate 1 |
| GSM2701890 |
pancreatic islets, wild type, 7 months HFD intervention, replicate 2 |
| GSM2701891 |
pancreatic islets, wild type, 7 months HFD intervention, replicate 3 |
| GSM2701892 |
pancreatic islets, wild type, 7 months HFD intervention, replicate 4 |
| GSM2701893 |
pancreatic islets, Tlr2/Tlr4 DKO, 7 months HFD intervention, replicate 1 |
| GSM2701894 |
pancreatic islets, Tlr2/Tlr4 DKO, 7 months HFD intervention, replicate 2 |
| GSM2701895 |
pancreatic islets, Tlr2/Tlr4 DKO, 7 months HFD intervention, replicate 3 |
| GSM2701896 |
pancreatic islets, Tlr2/Tlr4 DKO, 7 months HFD intervention, replicate 4 |
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| Relations |
| BioProject |
PRJNA394076 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE101392_RAW.tar |
58.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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