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"pageLength" : 12, "publishedYear" : 2020, "abstractText" : "Saturated fatty acids such as palmitate contribute to the development of Type 2 Diabetes by reducing insulin sensitivity, increasing inflammation and potentially contributing to anabolic resistance. We hypothesized that palmitate-induced ATP release from skeletal muscle cells may increase inflammatory cytokine production and contribute to insulin/anabolic resistance in an autocrine/paracrine manner. In C2C12 myotubes differentiated at physiological glucose concentrations (5.5 mM), palmitate treatment (16 h) at concentrations greater than 250 μM increased release of ATP and inflammatory cytokines IL-6 and MIF, significantly blunted insulin and amino acid-induced signaling and reduced mitochondrial function. In contrast to our hypothesis, degradation of extracellular ATP using apyrase, did not alter palmitate-induced insulin resistance nor alter release of cytokines. Moreover, treatment with ATPγS (16 h), a non-hydrolysable ATP analog, in the absence of palmitate, did not diminish insulin sensitivity. Acute treatment with ATPγS produced insulin mimetic roles; increased phosphorylation of PKB (aka AKT), S6K1 and ERK and enhanced GLUT4-mediated glucose uptake in the absence of exogenous insulin. The increases in PKB and S6K1 phosphorylation were completely prevented by pre-incubation with broad spectrum purinergic receptor (P2R) blockers PPADs and suramin but not by P2 × 4 or P2 × 7 blockers 5-BDBD or A-438079, respectively. Moreover, ATPγS increased IL-6 yet decreased MIF release, similar to the cytokine profile produced by exercise. Acute and chronic treatment with ATPγS increased glycolytic rate in a manner that was differentially inhibited by PPADs and suramin, suggesting heterogeneous P2R activation in the control of cellular metabolism. In summary, our data suggest that the palmitate-induced increase in ATP does not contribute to insulin/anabolic resistance in a cell autonomous manner.", "keywords" : [ { "otype" : "Keyword", "mtid" : 447, "link" : "/api/keyword/447", "label" : "PALMITATE", "published" : true, "oldId" : 447, "snippet" : true }, { "otype" : "Keyword", "mtid" : 4699, "link" : "/api/keyword/4699", "label" : "INSULIN SENSITIVITY", "published" : true, "oldId" : 4699, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1209830, "link" : "/api/keyword/1209830", "label" : "Mitochondrial function", "published" : true, "oldId" : 1209830, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1567293, "link" : "/api/keyword/1567293", "label" : "Macrophage migration inhibitory factor (MIF)", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1600302, "link" : "/api/keyword/1600302", "label" : "Interleukin 6 (IL-6)", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1856412, "link" : "/api/keyword/1856412", "label" : "adenosine 5'-triphosphate (ATP)", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 2177300, "link" : "/api/keyword/2177300", "label" : "skeletal muscle", "published" : true, "snippet" : true } ], "digital" : true, "printed" : null, "sourceYear" : 2020, "foreignEdition" : true, "foreignLanguage" : true, "fullPublication" : true, "conferencePublication" : false, "nationalOrigin" : false, "missingAuthor" : false, "oaType" : "GOLD", "oaCheckDate" : "2021-01-07", "oaFree" : false, "oaLink" : "http://www.frontiersin.org/physiology", "citationCount" : 0, "citationCountUnpublished" : 0, "citationCountWoOther" : 0, "independentCitCountWoOther" : 0, "doiCitationCount" : 0, "wosCitationCount" : 0, "scopusCitationCount" : 0, "independentCitationCount" : 0, "unhandledCitationCount" : 0, "citingPubCount" : 0, "independentCitingPubCount" : 0, "unhandledCitingPubCount" : 0, "citedPubCount" : 1, "citedCount" : 1, "ratings" : [ { "otype" : "SjrRating", "mtid" : 10879141, "link" : "/api/sjrrating/10879141", "label" : "sjr:Q2 (2020) Scopus - Physiology (medical) FRONTIERS IN PHYSIOLOGY 1664-042X", "listPos" : 31, "rankValue" : 0.49, "type" : "journal", "ratingType" : { "otype" : "RatingType", "mtid" : 10002, "link" : "/api/ratingtype/10002", "label" : "sjr", "code" : "sjr", "published" : true, "snippet" : true }, "subject" : { "otype" : "ClassificationExternal", "mtid" : 2737, "link" : "/api/classificationexternal/2737", "label" : "Scopus - Physiology (medical)", "published" : true, "oldId" : 2737, "snippet" : true }, "ranking" : "Q2", "calculation" : "FROM_LAST_YEAR", "published" : true, "snippet" : true } ], "ratingsForSort" : "Q2", "referenceList" : "Abdelmoez, A. 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