Messages from the Small Intestine Carried by Extracellular Vesicles in Prediabetes: A Proteomic Portrait.

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In the pathogenesis of type 2 diabetes, inter-organ communication plays an important role in its progress and metabolic surgery leads to its remission. Moreover, gut dysbiosis is emerging as a diabetogenic factor. However, it remains unclear how the gut senses metabolic alterations and whether this is transmitted to other tissues via EVs. Using a diet-induced prediabetic mouse model, we observed that protein packaging in gut-derived EVs (GDE), specifically the small intestine, is altered in prediabetes. Proteins related to lipid metabolism and to oxidative stress management were more abundant in prediabetic GDE compared to healthy controls. On the other hand, proteins related to glycolytic activity, as well as those responsible for the degradation of polyubiquitinated composites, were depleted in prediabetic GDE. Together, our findings show that protein packaging in GDE is markedly modified during prediabetes pathogenesis, thus suggesting that prediabetic alterations in the small intestine are translated into modified GDE proteomes, which are dispersed into the circulation where they can interact with and influence the metabolic status of other tissues. This study highlights the importance of the small intestine as a tissue that propagates prediabetic metabolic dysfunction throughout the body and the importance of GDE as the messengers. Data are available via ProteomeXchange with identifier PXD028338.", "claims": [{"id": "claim-method", "statement": "Difference significance was calculated through unpaired student’s-t tests with Welch’s correction; one-way ANOVA followed by Tukey–Kramer multiple comparison tests.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35263542", "locator": "sections[18] \"Statistical Analysis\" paragraph 2", "quote": "Difference significance was calculated through unpaired student’s-t tests with Welch’s correction; one-way ANOVA followed by Tukey–Kramer multiple comparison tests."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available via ProteomeXchange with identifier PXD028338.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35263542", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Data are available via ProteomeXchange with identifier PXD028338."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Together, our findings show that protein packaging in GDE is markedly modified during prediabetes pathogenesis, thus suggesting that prediabetic alterations in the small intestine are translated into modified GDE proteomes, which are dispersed into the circulation where they can interact with and influence the metabolic status of other tissues.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35263542", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Together, our findings show that protein packaging in GDE is markedly modified during prediabetes pathogenesis, thus suggesting that prediabetic alterations in the small intestine are translated into modified GDE proteomes, which are dispersed into the circulation where they can interact with and influence the metabolic status of other tissues."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Together, our findings show that protein packaging in GDE is markedly modified during prediabetes pathogenesis, thus suggesting that prediabetic alterations in the small intestine are translated into modified GDE proteomes, which are dispersed into the circulation where they can interact with and influence the metabolic status of other tissues.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35263542"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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