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Gregg 2016 Diabetes
Additional label 2016-08  +
Coupling states LEAK  + , OXPHOS  + , ET  +
Diseases Aging;senescence  +
Has abstract Aging is accompanied by impaired glucose h
Aging is accompanied by impaired glucose homeostasis and an increased risk of type 2 diabetes, culminating in the failure of insulin secretion from pancreatic β cells. To investigate the effects of age on β cell metabolism, we established a novel assay to directly image islet metabolism using NAD(P)H fluorescence lifetime imaging (FLIM). We determined that impaired mitochondrial activity underlies an age-dependent loss of insulin secretion in human islets. NAD(P)H FLIM revealed a comparable decline in mitochondrial function in the pancreatic islets of aged mice (≥ 24 months), resulting from 52% and 57% defects in flux through complex I and II of the electron transport chain. However, insulin secretion and glucose tolerance are preserved in aged mouse islets by the heightened metabolic sensitivity of the β cell triggering pathway, an adaptation clearly encoded in the metabolic and Ca<sub>2+</sub> oscillations that trigger insulin release (Ca<sub>2+</sub> plateau fraction: young, 0.211 ± 0.006; aged, 0.380 ± 0.007, P < 0.0001). This enhanced sensitivity is driven by a reduction in K<sub>ATP</sub> channel conductance (diazoxide: young, 5.1 ± 0.2 nS; aged, 3.5 ± 0.5 nS, P < 0.01), resulting in a ∼2.8 mM left shift in the β cell glucose threshold. Our results demonstrate how mice, but not humans, are able to successfully compensate for age-associated metabolic dysfunction by adjusting their β cell glucose sensitivity, and highlight an essential mechanism for ensuring the maintenance of insulin secretion. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
t for profit, and the work is not altered.  +
Has info [ PMID: 27284112]  +
Has title Gregg T, Poudel C, Schmidt BA, Dhillon RS,
Gregg T, Poudel C, Schmidt BA, Dhillon RS, Sdao SM, Truchan NA, Baar EL, Fernandez LA, Denu JM, Eliceiri KW, Rogers JD, Kimple ME, Lamming DW, Merrins MJ (2016) Pancreatic β cells from mice offset age-associated mitochondrial deficiency with reduced K<sub>ATP</sub> channel activity. Diabetes 65:2700-10.
gt; channel activity. Diabetes 65:2700-10.  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  + , Mouse  +
MiP area Respiration  + , Comparative MiP;environmental MiP  +
Pathways N  + , S  + , NS  + , ROX  +
Preparation Permeabilized tissue  +
Tissue and cell Islet cell;pancreas;thymus  + , Other cell lines  +
Was published by MiPNetLab US WI Madison Denu JM +
Was published in journal Diabetes +
Was published in year 2016  +
Was written by Gregg T + , Poudel C + , Schmidt BA + , Dhillon RS + , Sdao SM + , Truchan NA + , Baar EL + , Fernandez LA + , Denu JM + , Eliceiri KW + , Rogers JD + , Kimple ME + , Lamming DW + , Merrins MJ +
Categories Publications
Modification date
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12:25:26, 13 November 2017  +
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