Reynolds 2016 Am J Physiol Endocrinol Metab: Difference between revisions
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{{Publication | {{Publication | ||
|title=Reynolds MS, Hancock CR, Ray JD, Kener KB, Draney C, Garland K, Hardman J, Bikman BT, Tessem JS (2016) ฮฒ-cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion. Am J Physiol Endocrinol Metab [Epub ahead of print]. ย | |title=Reynolds MS, Hancock CR, Ray JD, Kener KB, Draney C, Garland K, Hardman J, Bikman BT, Tessem JS (2016) ฮฒ-cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion. Am J Physiol Endocrinol Metab [Epub ahead of print]. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/27221116 PMID: 27221116] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/27221116 PMID: 27221116] | ||
|authors=Reynolds MS, Hancock CR, Ray JD, Kener KB, Draney C, Garland K, Hardman J, Bikman BT, Tessem JS | |authors=Reynolds MS, Hancock CR, Ray JD, Kener KB, Draney C, Garland K, Hardman J, Bikman BT, Tessem JS | ||
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Copyright ยฉ 2016, American Journal of Physiology - Endocrinology and Metabolism. | Copyright ยฉ 2016, American Journal of Physiology - Endocrinology and Metabolism. | ||
|keywords=Beta cell, Nr4a1, Nr4a3, Insulin secretion, Mitochondrial respiration | |keywords=Beta cell, Nr4a1, Nr4a3, Insulin secretion, Mitochondrial respiration | ||
|mipnetlab=US UT Provo Hancock CR | |mipnetlab=US UT Provo Hancock CR, SG Singapore Hausenloy DJ, US UT Provo Bikman BT | ||
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Revision as of 10:45, 27 June 2016
Reynolds MS, Hancock CR, Ray JD, Kener KB, Draney C, Garland K, Hardman J, Bikman BT, Tessem JS (2016) ฮฒ-cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion. Am J Physiol Endocrinol Metab [Epub ahead of print]. |
Reynolds MS, Hancock CR, Ray JD, Kener KB, Draney C, Garland K, Hardman J, Bikman BT, Tessem JS (2016) Am J Physiol Endocrinol Metab
Abstract: Iฮฒ-cell insulin secretion is dependent on proper mitochondrial function. Various studies have clearly shown that the Nr4a family of orphan nuclear receptors is essential for fuel utilization and mitochondrial function in liver, muscle and adipose. We have previously demonstrated that overexpression of Nr4a1 or Nr4a3 is sufficient to induce proliferation of pancreatic ฮฒ-cells. In this study we examined whether Nr4a expression impacts pancreatic ฮฒ-cell mitochondrial function. Here we show that ฮฒ-cell mitochondrial respiration is dependent on the nuclear receptors Nr4a1 and Nr4a3. Mitochondrial respiration in permeabilized cells was significantly decreased in ฮฒ-cells lacking Nr4a1 or Nr4a3. Furthermore, respiration rates of intact cells deficient for Nr4a1 or Nr4a3 in the presence of 16mM glucose resulted in decreased glucose mediated oxygen consumption. Consistent with this reduction in respiration, a significant decrease in glucose stimulated insulin secretion rates is observed with deletion of Nr4a1 or Nr4a3. Interestingly, the changes in respiration and insulin secretion occur without a reduction in mitochondrial content, suggesting decreased mitochondrial function. We establish that knockdown of Nr4a1 and Nr4a3 results in decreased expression of the mitochondrial dehydrogenase subunits Idh3g and Sdhb. We demonstrate that loss of Nr4a1 and Nr4a3 impedes production of ATP, and ultimately inhibits glucose stimulated insulin secretion. These data demonstrate for the first time that the orphan nuclear receptors Nr4a1 and Nr4a3 are critical for ฮฒ-cell mitochondrial function and insulin secretion.
Copyright ยฉ 2016, American Journal of Physiology - Endocrinology and Metabolism. โข Keywords: Beta cell, Nr4a1, Nr4a3, Insulin secretion, Mitochondrial respiration
โข O2k-Network Lab: US UT Provo Hancock CR, SG Singapore Hausenloy DJ, US UT Provo Bikman BT
Labels: MiParea: Respiration, Genetic knockout;overexpression
Tissue;cell: Islet cell;pancreas;thymus Preparation: Intact cells, Permeabilized cells
HRR: Oxygraph-2k
Labels, 2016-06