{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe study by de Boer et al"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "identified miR‑5190 as one of four circulating microRNAs whose plasma levels are significantly altered in type 1 diabetes. Notably, miR‑5190 levels were negatively correlated with hemoglobin A1c, implying that lower miR‑5190 expression is associated with higher hyperglycemia. In silico pathway analyses further revealed that the target genes of miR‑5190 (along with three other miRNAs) are enriched in multiple signaling cascades, most prominently in the axon guidance pathway, as well as pathways such as Rap1 signaling, focal adhesion, and neurotrophin signaling. These findings suggest that miR‑5190 may play a role in modulating pathways that contribute to diabetes‐related complications.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional insights into the regulation of cellular signaling come from studies examining adhesion G protein‑coupled receptors. For example, research focusing on the brain-specific angiogenesis inhibitor (BAI) subfamily demonstrated that the ELMO/DOCK/Rac pathway is engaged through interactions with the cytoplasmic tails of these receptors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Although miR‑5190 is not directly analyzed in this context, the enrichment of axon guidance and neurotrophin signaling pathways—key processes governed in part by receptor-mediated mechanisms—hints at a broader framework where miR‑5190’s regulatory effects may intersect with receptor signaling networks.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary functional studies involving the knockout of Gpr128 further underscore the importance of receptor-based signaling in maintaining cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " While these investigations primarily address the biological role of GPR128, the mechanistic overlap noted in pathways such as focal adhesion and neurotrophin signaling suggests that miR‑5190’s modulation of its target transcripts might influence similar signaling networks. Together, these studies indicate that dysregulation of miR‑5190 could contribute to the development of complications in diabetes by altering key molecular pathways that are also modulated by receptor-mediated signaling.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eiichiro Satake, Marcus G Pezzolesi, Zaipul I Md Dom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db17-1207"}], "href": "https://doi.org/10.2337/db17-1207"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29453204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29453204"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhuangfeng Weng, Chenghao Situ, Lin Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of BAI1/ELMO2 complex reveals an action mechanism of adhesion GPCRs via ELMO family scaffolds."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-07938-9"}], "href": "https://doi.org/10.1038/s41467-018-07938-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30604775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30604775"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ying-Yin Ni, Yan Chen, Shun-Yuan Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of Gpr128 results in weight loss and increased intestinal contraction frequency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Gastroenterol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3748/wjg.v20.i2.498"}], "href": "https://doi.org/10.3748/wjg.v20.i2.498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24574718"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24574718"}]}]}]}