{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js?nzn96p\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js?nzn96p\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;12\\\/16\\\/26\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;12\\\/16\\\/26\u0022}],\u0022ac\u0022:{\u0022spmdc;12\\\/16\\\/26\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;12\\\/16\\\/26\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EIn 2011, 366 million people had diabetes; by 2030, that figure is projected to rise to 552 million [International Diabetes Federation. \u003Cem\u003EIDF Diabetes Atlas\u003C\/em\u003E. 5th ed. 2009]. The search for novel oral antidiabetic drugs has taken on a growing sense of urgency. This article discusses efforts underway to develop glucagon-based incretin hybrids.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin Diabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EIn 2011, 366 million people had diabetes; by 2030, that figure is projected to rise to 552 million [International Diabetes Federation. \u003Cem\u003EIDF Diabetes Atlas.\u003C\/em\u003E 5th ed. 2009]. The search for novel oral antidiabetic drugs (OADs) has taken on a growing sense of urgency. Richard D. DiMarchi, PhD, Indiana University, Bloomington, Indiana, USA, discussed efforts underway to develop glucagon-based incretin hybrids.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EDr. DiMarchi focused his discussion on 2 glucagon-based single molecule coagonists: glucagon\/glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP)\/GLP-1. The clinical benefits of each are shown in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E. The glucagon\/GLP-1 coagonist hypothesis is that chronic glucagon action decreases fat mass by increasing energy expenditure via the glucagon receptor, GLP-1 decreases fat mass by reducing food intake via the GLP-1 receptor, a GLP-1\/glucagon coagonist might decrease fat mass by synergistically affecting both components via 2 receptors, and a GLP-1\/glucagon coagonist should minimize the diabetogenic risk of a pure glucagon analogue.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/13066\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/13066\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13066\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003ESummary of Glucagon-Based Single Molecule Coagonists.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-6\u0022\u003ESeveral parts of the hypothesis have been proven in preclinical and clinical studies. Day et al. [\u003Cem\u003ENat Chem Biol\u003C\/em\u003E 2009] reported a new peptide with agonism at the glucagon and GLP-1 receptors that has potent, sustained satiation-inducing and lipolytic effects. Two coagonist peptides that differ from each other only in their levels of glucagon receptor agonism were studied in rodent obesity models. Administration of PEGylated peptides once per week normalized adiposity and glucose tolerance in diet-induced obese (DIO) mice.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EPreclinical evidence also indicates that high-activity, long-acting leptin analogues are additively efficacious when used with other weight-lowering agents, ie, extendin-4 or fibroblast growth factor 21 (FGF21; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Muller TD et al. \u003Cem\u003EJ Pept Sci\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/26\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022High-Activity, Long-Acting Leptin Analogues May Be Additively Efficacious When Used with Other Weight-Lowering Agents.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-263818592\u0022 data-figure-caption=\u0022High-Activity, Long-Acting Leptin Analogues May Be Additively Efficacious When Used with Other Weight-Lowering Agents.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/26\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/26\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/16\/26\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13064\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EHigh-Activity, Long-Acting Leptin Analogues May Be Additively Efficacious When Used with Other Weight-Lowering Agents.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from RD DiMarchi, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EWhile Schelshorn et al. [\u003Cem\u003EMol Pharmacol\u003C\/em\u003E 2012] demonstrated that GLP-1 induces G-protein-coupled receptor heteromer formation, Christensen et al. [\u003Cem\u003EDiabetes\u003C\/em\u003E 2011] found that GIP appears to be a physiological bifunctional blood glucose stabilizer with diverging glucose-dependent effects on the 2 main pancreatic glucoregulatory hormones in healthy human subjects.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EBased on the data, Dr. DiMarchi concluded that GLP-1 agonists provide significant clinical benefits, yet glucagon\/GLP-1 and GIP\/GLP-1 coagonists deliver significantly greater activity than GLP-1 in animals. The addition of leptin provides additional efficacy in DIO mice.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ETargeting the Glucocorticoid Pathway\u003C\/h2\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EAndr\u00e9 J. Scheen, MD, PhD, University of Li\u00e8ge, Li\u00e8ge, Belgium, addressed the question of whether there is any role of cortisol in the prevention of hyperglycemia in type 2 diabetes mellitus (T2DM). He discussed similarities between T2DM, metabolic syndrome, and Cushing syndrome; the role of cortisol on activation of the hypothalamic-pituitary-adrenal \u003Cem\u003Eaxis\u003C\/em\u003E and local tissue regulation; the role of 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1) in adipose tissue and the liver; the effects of 11\u03b2-HSD1 inhibition (knockout models and chemical inhibitors) in rodents; the effects of selective 11\u03b2-HSD1 inhibitors in humans with T2DM (and metabolic syndrome); and limitations and perspectives.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EHollis and Huber [\u003Cem\u003EDiabetes Obes Metab\u003C\/em\u003E 2011] reported that 11\u03b2-HSD1 catalyzes the intracellular conversion of inert cortisone to physiologically active cortisol, enhancing local cortisol action beyond what would be predicted based on simple plasma exposures.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EResults of a 12-week, placebo-controlled dose-ranging efficacy study by Rosenstock et al. [\u003Cem\u003EDiabetes Care\u003C\/em\u003E 2010] provided the first evidence that decreasing local cortisol exposure through selective 11\u03b2-HSD1 inhibition can improve hyperglycemia in T2DM. Treatment with INCB13739 showed statistically significant reductions in HbA1C in the 100-mg (\u22120.47%; p\u0026lt;0.05) and 200-mg (\u22120.56%; p\u0026lt;0.01) groups. The 200-mg group also achieved significant reductions relative to placebo in fasting plasma glucose (\u221224 mg\/dL) and homeostasis model assessment-insulin resistance (\u221224%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EIn obese men with T2DM, liver 11\u03b2-HSD1 is increased, whereas liver 11\u03b2-HSD1 is sustained in obese euglycemic men. This supports the concept that inhibitors of 11\u03b2-HSD1 are likely to be most effective in obese T2DM subjects [Stimson RH et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EIn addition to 11\u03b2-HSD1 inhibitors, which reduce the glucocorticoid effects in liver and fat, other novel approaches to glycemic regulation include the use of sodium-glucose cotransporter 2 inhibitors, which increase renal glucose elimination. Insulin glucokinase activators and pancreatic-G-protein-coupled fatty-acid receptor agonists, glucagon receptor antagonists, and metabolic inhibitors of hepatic glucose output are being assessed. Early proof of principle has been shown for compounds that enhance and partly mimic insulin action and replicate some effects of bariatric surgery [Tahrani AA et al. \u003Cem\u003ELancet\u003C\/em\u003E 2011].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EEnhancing the Action of Insulin\u003C\/h2\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EStefano Del Prato, MD, University of Pisa, Pisa, Italy, discussed new routes to enhancing the action of insulin.\u003C\/p\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EMa et al. [\u003Cem\u003EMol Cell Biochem\u003C\/em\u003E 2011] have investigated the effects of compound CCF06240, a PTP1B inhibitor, on insulin sensitivity and lipid abnormalities \u003Cem\u003Ein vivo\u003C\/em\u003E and \u003Cem\u003Ein vitro.\u003C\/em\u003E PTP1B is a negative regulator of the insulin signaling pathway. Results demonstrate that CCF06240 could increase insulin sensitivity through the regulation of the insulin signaling pathway, and decrease free fatty acid-insulin-induced hepatocytes lipid accumulation by reducing fatty acid synthesis.\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003EConti et al. [\u003Cem\u003EDiabetes\u003C\/em\u003E 2011] developed teglicar, a new form of antihyperglycemic agent, through the selective and reversible inhibition of the liver isoform of carnitine palmitoyl-transferase 1. Investigation of glucose production took place in isolated hepatocytes and during pancreatic clamps in healthy rats. The researchers performed chronic treatments on C57BL\/6J, db\/db, high-fat fed mice, and rats to understand glucose metabolism and insulin sensitivity.\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EIn isolated hepatocytes, teglicar concentration dependently reduced ketone bodies and glucose production up to 72% and 50%, respectively. Antidiabetic activity in hepatocytes and rats was associated with improved insulin sensitivity assessed by the insulin tolerance test. In high-fat fed C57BL\/6J mice, long-term teglicar administration normalized glycemia (\u221219%) and insulinemia (\u221253%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003EMembers of the fibroblast growth factor family stimulate glucose uptake and update mitochondrial function in key metabolic tissues [Cant\u00f3 C, Auwerx J. \u003Cem\u003EScience\u003C\/em\u003E 2012]. FGF21 has become particularly interesting as exongenous administration to animal models of diabetes and obesity is generally associated with weight loss [Muise ES et al. \u003Cem\u003EMol Pharmacol\u003C\/em\u003E 2008; Kharitonenkov A et al. \u003Cem\u003EEndocrinology\u003C\/em\u003E 2007]. The understanding of FGF21 biology is still evolving.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/16\/26.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzn96p\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn96p\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzn96p\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}