{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent genetic studies have implicated SLC16A11 as an important factor in type 2 diabetes risk. The gene, which is primarily expressed in the liver and localizes to the endoplasmic reticulum, encodes a proton‐coupled monocarboxylate transporter. Risk haplotypes of SLC16A11—which carry several amino acid substitutions—are associated with altered transporter function that leads to modifications in lipid metabolism, including increased intracellular triacylglycerol levels. These findings, observed in diverse populations, have highlighted a potential mechanism whereby perturbations in monocarboxylate transport contribute to disturbed fatty acid handling and diabetes susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther investigations using both human cohorts and animal models have deepened our understanding of SLC16A11’s role in metabolic regulation. In vivo studies demonstrate that while complete loss of SLC16A11 may not lead to overt metabolic defects, reintroduction of the mutant form can trigger triglyceride accumulation and insulin resistance—potentially via upregulation of lipid regulatory factors such as lipin 1—and impair cell-surface localization through disrupted interactions with accessory proteins like basigin. Population-based analyses have also associated risk variants with altered liver enzymes, adipocyte morphology, and differences in circulating lipid and glucose levels, particularly among individuals of Mexican and Latin American descent; however, variability in genetic effects across other ethnic groups has been noted."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence further suggests that additional layers of regulation—such as epigenetic modifications in gestational diabetes and interactions with immunologic determinants like HLA-DRB1 alleles—may modulate the impact of SLC16A11 variants on metabolic homeostasis. Collectively, these studies underscore a multifaceted role for SLC16A11 in hepatic lipid and monocarboxylate transport, influencing insulin sensitivity and the broader pathophysiology of type 2 diabetes. Such insights pave the way for exploring therapeutic strategies targeting SLC16A11 function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Amy L Williams, Suzanne B R Jacobs, Hortensia Moreno-Macías, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature12828"}], "href": "https://doi.org/10.1038/nature12828"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24390345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24390345"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "J C Lara-Riegos, M G Ortiz-López, B I Peña-Espinoza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diabetes susceptibility in Mayas: Evidence for the involvement of polymorphisms in HHEX, HNF4α, KCNJ11, PPARγ, CDKN2A/2B, SLC30A8, CDC123/CAMK1D, TCF7L2, ABCA1 and SLC16A11 genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2015.03.065"}], "href": "https://doi.org/10.1016/j.gene.2015.03.065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25839936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25839936"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Victor Rusu, Eitan Hoch, Josep M Mercader, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db15-0571"}], "href": "https://doi.org/10.2337/db15-0571"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26487785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26487785"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "América L Miranda-Lora, Miguel Cruz, Mario Molina-Díaz, et al. 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