Publication Date:
2013-11-10
Description:
Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as 'glucose effectiveness', account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983910/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwartz, Michael W -- Seeley, Randy J -- Tschop, Matthias H -- Woods, Stephen C -- Morton, Gregory J -- Myers, Martin G -- D'Alessio, David -- DK083042/DK/NIDDK NIH HHS/ -- DK089053/DK/NIDDK NIH HHS/ -- DK093848/DK/NIDDK NIH HHS/ -- P30 DK017047/DK/NIDDK NIH HHS/ -- P30 DK035816/DK/NIDDK NIH HHS/ -- R01 DK083042/DK/NIDDK NIH HHS/ -- R01 DK089056/DK/NIDDK NIH HHS/ -- R01 DK090320/DK/NIDDK NIH HHS/ -- England -- Nature. 2013 Nov 7;503(7474):59-66. doi: 10.1038/nature12709.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24201279" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Blood Glucose/metabolism
;
Brain/*metabolism
;
Diabetes Mellitus/*metabolism
;
Glucose/*metabolism
;
*Homeostasis
;
Humans
;
Insulin/metabolism
;
Islets of Langerhans/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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