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000165605 0247_ $$2doi$$a10.1016/j.celrep.2022.111698
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000165605 037__ $$aDZNE-2022-01738
000165605 041__ $$aEnglish
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000165605 1001_ $$aBakker, Wineke$$b0
000165605 245__ $$aAcute changes in systemic glycemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis.
000165605 260__ $$a[New York, NY]$$bElsevier$$c2022
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000165605 520__ $$aTherapies based on glucagon-like peptide-1 (GLP-1) long-acting analogs and insulin are often used in the treatment of metabolic diseases. Both insulin and GLP-1 receptors are expressed in metabolically relevant brain regions, suggesting a cooperative action. However, the mechanisms underlying the synergistic actions of insulin and GLP-1R agonists remain elusive. In this study, we show that insulin-induced hypoglycemia enhances GLP-1R agonists entry in hypothalamic and area, leading to enhanced whole-body fat oxidation. Mechanistically, this phenomenon relies on the release of tanycyctic vascular endothelial growth factor A, which is selectively impaired after calorie-rich diet exposure. In humans, low blood glucose also correlates with enhanced blood-to-brain passage of insulin, suggesting that blood glucose gates the passage other energy-related signals in the brain. This study implies that the preventing hyperglycemia is important to harnessing the full benefit of GLP-1R agonist entry in the brain and action onto lipid mobilization and body weight loss.
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000165605 650_7 $$2Other$$aCP: Metabolism
000165605 650_7 $$2Other$$abrain access
000165605 650_7 $$2Other$$adiabetes
000165605 650_7 $$2Other$$aglucagon-like peptide 1 analogs
000165605 650_7 $$2Other$$aglycemic control
000165605 650_7 $$2Other$$ametabolism
000165605 650_7 $$2Other$$anutrient partitioning
000165605 650_7 $$2Other$$aobesity
000165605 650_7 $$2Other$$atanycyte
000165605 650_7 $$2NLM Chemicals$$aBlood Glucose
000165605 650_7 $$2NLM Chemicals$$aVascular Endothelial Growth Factor A
000165605 650_7 $$089750-14-1$$2NLM Chemicals$$aGlucagon-Like Peptide 1
000165605 650_7 $$2NLM Chemicals$$aInsulin
000165605 650_2 $$2MeSH$$aHumans
000165605 650_2 $$2MeSH$$aBlood Glucose: metabolism
000165605 650_2 $$2MeSH$$aVascular Endothelial Growth Factor A: metabolism
000165605 650_2 $$2MeSH$$aGlucagon-Like Peptide 1: metabolism
000165605 650_2 $$2MeSH$$aInsulin: metabolism
000165605 650_2 $$2MeSH$$aHomeostasis
000165605 650_2 $$2MeSH$$aBrain: metabolism
000165605 7001_ $$aImbernon, Monica$$b1
000165605 7001_ $$aSalinas, Casper Gravesen$$b2
000165605 7001_ $$aMoro Chao, Daniela Herrera$$b3
000165605 7001_ $$aHassouna, Rim$$b4
000165605 7001_ $$aMorel, Chloe$$b5
000165605 7001_ $$aMartin, Claire$$b6
000165605 7001_ $$aLeger, Caroline$$b7
000165605 7001_ $$aDenis, Raphael G P$$b8
000165605 7001_ $$aCastel, Julien$$b9
000165605 7001_ $$aPeter, Andreas$$b10
000165605 7001_ $$aHeni, Martin$$b11
000165605 7001_ $$0P:(DE-2719)2810915$$aMaetzler, Walter$$b12$$udzne
000165605 7001_ $$aNielsen, Heidi Solvang$$b13
000165605 7001_ $$aDuquenne, Manon$$b14
000165605 7001_ $$aSchwaninger, Markus$$b15
000165605 7001_ $$aLundh, Sofia$$b16
000165605 7001_ $$aJohan Hogendorf, Wouter Frederic$$b17
000165605 7001_ $$aGangarossa, Giuseppe$$b18
000165605 7001_ $$aSecher, Anna$$b19
000165605 7001_ $$aHecksher-Sørensen, Jacob$$b20
000165605 7001_ $$aPedersen, Thomas Åskov$$b21
000165605 7001_ $$aPrevot, Vincent$$b22
000165605 7001_ $$aLuquet, Serge$$b23
000165605 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2022.111698$$gVol. 41, no. 8, p. 111698 -$$n8$$p111698$$tCell reports$$v41$$x2211-1247$$y2022
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