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Enhanced Insulin Sensitivity by Adipose Tissue Browning Alters Islet Morphology and Hormone Secretion in Response to Autonomic Nervous Activation in Female Mice.

Omar, Bilal LU ; Kvist Reimer, Martina LU ; Enerback, Sven and Ahrén, Bo LU (2016) In American Journal of Physiology: Endocrinology and Metabolism 310(1). p.81-90
Abstract
Insulin resistance results in compensatory increase in insulin secretion to maintain normoglycemia. Conversely, high insulin sensitivity results in reduced insulin secretion to prevent hypoglycemia. The mechanisms for this inverse adaptation are not well understood. We utilized highly insulin sensitive mice, due to adipocyte specific overexpression of the FOXC2 transcription factor, to study mechanisms of the reversed islet adaptation to increased insulin sensitivity. We found that Foxc2TG mice responded to mild hyperglycemia with reduced insulin secretion compared to wild type mice, however when severe hyperglycemia was induced, Foxc2TG mice demonstrated insulin secretion equal to or greater than that of wild type mice. In response to... (More)
Insulin resistance results in compensatory increase in insulin secretion to maintain normoglycemia. Conversely, high insulin sensitivity results in reduced insulin secretion to prevent hypoglycemia. The mechanisms for this inverse adaptation are not well understood. We utilized highly insulin sensitive mice, due to adipocyte specific overexpression of the FOXC2 transcription factor, to study mechanisms of the reversed islet adaptation to increased insulin sensitivity. We found that Foxc2TG mice responded to mild hyperglycemia with reduced insulin secretion compared to wild type mice, however when severe hyperglycemia was induced, Foxc2TG mice demonstrated insulin secretion equal to or greater than that of wild type mice. In response to autonomic nervous activation the acute suppression of insulin seen in wild-type mice was absent in Foxc2TG mice suggesting impaired adrenergic signaling in the islet. Basal glucagon was increased in Foxc2TG mice but they displayed severely impaired glucagon responses to cholinergic and autonomic nervous stimuli. These data suggest that the autonomic nerves contribute to the islet adaptation to high insulin sensitivity which is compatible with a neuro-adipo regulation of islet function being instrumental for maintaining glucose regulation. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Endocrinology and Metabolism
volume
310
issue
1
pages
81 - 90
publisher
American Physiological Society
external identifiers
  • pmid:26530152
  • wos:000366597200009
  • scopus:84949564058
ISSN
1522-1555
DOI
10.1152/ajpendo.00296.2015
language
English
LU publication?
yes
id
b8f323d5-c886-4ba2-a3c9-18613c8242b3 (old id 8243431)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26530152?dopt=Abstract
date added to LUP
2015-12-02 18:08:38
date last changed
2017-01-01 03:27:54
@article{b8f323d5-c886-4ba2-a3c9-18613c8242b3,
  abstract     = {Insulin resistance results in compensatory increase in insulin secretion to maintain normoglycemia. Conversely, high insulin sensitivity results in reduced insulin secretion to prevent hypoglycemia. The mechanisms for this inverse adaptation are not well understood. We utilized highly insulin sensitive mice, due to adipocyte specific overexpression of the FOXC2 transcription factor, to study mechanisms of the reversed islet adaptation to increased insulin sensitivity. We found that Foxc2TG mice responded to mild hyperglycemia with reduced insulin secretion compared to wild type mice, however when severe hyperglycemia was induced, Foxc2TG mice demonstrated insulin secretion equal to or greater than that of wild type mice. In response to autonomic nervous activation the acute suppression of insulin seen in wild-type mice was absent in Foxc2TG mice suggesting impaired adrenergic signaling in the islet. Basal glucagon was increased in Foxc2TG mice but they displayed severely impaired glucagon responses to cholinergic and autonomic nervous stimuli. These data suggest that the autonomic nerves contribute to the islet adaptation to high insulin sensitivity which is compatible with a neuro-adipo regulation of islet function being instrumental for maintaining glucose regulation.},
  author       = {Omar, Bilal and Kvist Reimer, Martina and Enerback, Sven and Ahrén, Bo},
  issn         = {1522-1555},
  language     = {eng},
  number       = {1},
  pages        = {81--90},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Endocrinology and Metabolism},
  title        = {Enhanced Insulin Sensitivity by Adipose Tissue Browning Alters Islet Morphology and Hormone Secretion in Response to Autonomic Nervous Activation in Female Mice.},
  url          = {http://dx.doi.org/10.1152/ajpendo.00296.2015},
  volume       = {310},
  year         = {2016},
}