| Brain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion. | |
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MedLine Citation:
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PMID: 22210318 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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As patients decline from health to type 2 diabetes, glucose-stimulated insulin secretion (GSIS) typically becomes impaired. Although GSIS is driven predominantly by direct sensing of a rise in blood glucose by pancreatic β-cells, there is growing evidence that hypothalamic neurons control other aspects of peripheral glucose metabolism. Here we investigated the role of the brain in the modulation of GSIS. To examine the effects of increasing or decreasing hypothalamic glucose sensing on glucose tolerance and insulin secretion, glucose or inhibitors of glucokinase, respectively, were infused into the third ventricle during intravenous glucose tolerance tests (IVGTTs). Glucose-infused rats displayed improved glucose handling, particularly within the first few minutes of the IVGTT, with a significantly lower area under the excursion curve within the first 10 min (AUC0-10). This was explained by increased insulin secretion. In contrast, infusion of the glucokinase inhibitors glucosamine or mannoheptulose worsened glucose tolerance and decreased GSIS in the first few minutes of IVGTT. Our data suggest a role for brain glucose sensors in the regulation of GSIS, particularly during the early phase. We propose that pharmacological agents targeting hypothalamic glucose-sensing pathways may represent novel therapeutic strategies for enhancing early phase insulin secretion in type 2 diabetes. |
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Authors:
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Mayowa A Osundiji; Daniel D Lam; Jill Shaw; Chen-Yu Yueh; S Pauliina Markkula; Paul Hurst; Carolina Colliva; Aldo Roda; Lora K Heisler; Mark L Evans |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-12-30 |
Journal Detail:
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Title: Diabetes Volume: 61 ISSN: 1939-327X ISO Abbreviation: Diabetes Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-25 Completed Date: 2012-03-13 Revised Date: 2012-04-02 |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: United States |
Other Details:
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Languages: eng Pagination: 321-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, University of Cambridge Metabolic Research Laboratories, and National Institute for Health Research, Cambridge Biomedical Research Centre, Cambridge, UK |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Glucokinase / physiology Glucose / metabolism*, pharmacology Glucose Tolerance Test Hypothalamus / drug effects, physiology* Injections, Intraventricular Insulin / secretion* Male Mannoheptulose / pharmacology Pancreas / secretion* Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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081713//Wellcome Trust; DK065171/DK/NIDDK NIH HHS; WT081713//Wellcome Trust; //Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Insulin; 50-99-7/Glucose; 654-29-5/Mannoheptulose; EC 2.7.1.2/Glucokinase |
| Comments/Corrections | |
Comment In:
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Diabetes. 2012 Mar;61(3):564-5
[PMID:
22354931
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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