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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\u003EGLP-1 is secreted in response to food ingestion, although the action of glucagon-like peptide\u20131 on brain glucose metabolism has been hypothesized but has not yet been established. This article presents results from the Effect of Exenatide on Brain, Adipose Tissue, Pancreas, and Liver Function study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01588418\u0026amp;atom=%2Fspmdc%2F14%2F32%2F19.atom\u0022\u003ENCT01588418\u003C\/a\u003E], a phase 4 clinical trial that aimed to evaluate the effect of a single injection of exenatide (a GLP-1 agonist) on cerebral glucose metabolism during an oral glucose tolerance test.\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\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHyperglycemia\/Hypoglycemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EAmalia Gastaldelli, PhD, Research Director of the Cardiometabolic Risk Unit at the Institute of Clinical Physiology, CNR, Pisa, Italy, and Adjunct Associate Professor at the University of Texas Health Science Center, San Antonio, Texas, USA, presented results from the Effect of Exenatide on Brain, Adipose Tissue, Pancreas, and Liver Function study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01588418\u0026amp;atom=%2Fspmdc%2F14%2F32%2F19.atom\u0022\u003ENCT01588418\u003C\/a\u003E], of which she was the principal investigator. This is a phase 4 clinical trial that aimed to evaluate the effect of a single injection of exenatide (a glucagon-like peptide\u20131 [GLP-1] agonist) on cerebral glucose metabolism during an oral glucose tolerance test (OGTT).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EGLP-1 is secreted in response to food ingestion. The molecule stimulates insulin secretion, suppresses glucagon secretion, and delays gastric emptying [Campbell JE, Drucker DJ. \u003Cem\u003ECell Metab\u003C\/em\u003E 2013; Nauck et al. \u003Cem\u003EDiabetologia\u003C\/em\u003E 2011; Holst JJ. \u003Cem\u003ECurr Opin Pharmacol\u003C\/em\u003E 2013]. GLP-1 also has effects outside the pancreas, including suppression of appetite [Gejl et al. \u003Cem\u003EBasic Clin Pharmacol Toxicol\u003C\/em\u003E 2014]. The action of GLP-1 on brain glucose metabolism has been hypothesized but has not yet been established [Alvarez et al. \u003Cem\u003EJ Neurochem\u003C\/em\u003E 2005]. A few studies have looked for effects of GLP-1 on human brain metabolism [Pannaciulli et al. \u003Cem\u003ENeuroimage\u003C\/em\u003E 2007; Lerche et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2008; Gejl et al. \u003Cem\u003EJ Cereb Blood Flow Metab\u003C\/em\u003E 2012], but none of these examined response to a glucose load.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn this phase 4 clinical trial, a total of 15 men, either without diabetes and with impaired glucose tolerance or with newly diagnosed type 2 diabetes mellitus (T2DM) at screening, each underwent 2 double-blind studies in randomized order consisting of subcutaneous injection of exenatide 5 \u03bcg or placebo 30 minutes before OGTT. Brain imaging was performed by positron emission tomography beginning 60 minutes after intravenous administration of the radioactive glucose analog \u003Csup\u003E18\u003C\/sup\u003EF-FDG simultaneous with oral glucose 75 g and [U- \u003Csup\u003E13\u003C\/sup\u003EC] glucose 1.5 g.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EPatients who received exenatide displayed about 40% more glucose uptake in the brain overall, as well as in the frontal, temporal, parietal, and occipital lobes. On average, glucose was markedly higher in areas of the brain known to be involved in glucose homeostasis, such as the limbic system, insula, and putamen. A similar trend was seen for areas associated with the food-intake reward system, with higher uptake in the orbitofrontal cortex, the thalamus, the anterior and posterior cingulate, and, again, the putamen and limbic system (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E; \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .05). Dr Gastaldelli noted that uptake in the hypothalamus, on the contrary, was distinctly lower.\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\/14\/32\/19\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effect of Exenatide on Glucose Levels in the Brain\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2111684544\u0022 data-figure-caption=\u0022Effect of Exenatide on Glucose Levels in the Brain\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\/14\/32\/19\/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\/14\/32\/19\/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\/14\/32\/19\/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\/12041\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-6\u0022 class=\u0022first-child\u0022\u003EEffect of Exenatide on Glucose Levels in the Brain\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from A Gastaldelli, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EDr Gastaldelli said that the question of whether endogenous glucose production (EGP) is controlled by the brain is still a matter of debate and that the researchers had also looked for clues on the topic of EGP regulation by the brain in the study data. Although a correlation between oral glucose rate of appearance and glucose uptake in areas implicated in glucose homeostasis with exenatide treatment was noted (R\u003Csup\u003E2\u003C\/sup\u003E = 0.642; \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .009), no correlation between suppression of EGP and cerebral glucose uptake in the areas implicated in glucose homeostasis was observed.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EIn conclusion, Dr Gastaldelli stated that, overall, the results of the trial demonstrate the profound effect that exenatide exerts on cerebral glucose metabolism following ingestion of an oral glucose load.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 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\/14\/32\/19.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?nzorq2\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?nzorq2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}