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Evidence for time dependent variation of glucagon secretion in mice.

Malmgren, Siri LU and Ahrén, Bo LU (2016) In Peptides 76. p.102-107
Abstract
Glucose metabolism is subjected to diurnal variation, which might be mediated by alterations in the transcription pattern of clock genes and regulated by hormonal factors, as has been demonstrated for insulin. However, whether also glucagon is involved in the diurnal variation of glucose homeostasis is not known. We therefore examined glucagon secretion after meal ingestion (meal tolerance test) and during hypoglycemia (hyperinsulinemic hypoglycemic clamp at 2.5mmol/L glucose) and in vitro from isolated islets at ZT3 versus ZT15 in normal C57BL/6J mice and, furthermore, glucose levels and the insulin response to meal ingestion were also examined at these time points in glucagon receptor knockout mice (GCGR-/-) and their wildtype (wt)... (More)
Glucose metabolism is subjected to diurnal variation, which might be mediated by alterations in the transcription pattern of clock genes and regulated by hormonal factors, as has been demonstrated for insulin. However, whether also glucagon is involved in the diurnal variation of glucose homeostasis is not known. We therefore examined glucagon secretion after meal ingestion (meal tolerance test) and during hypoglycemia (hyperinsulinemic hypoglycemic clamp at 2.5mmol/L glucose) and in vitro from isolated islets at ZT3 versus ZT15 in normal C57BL/6J mice and, furthermore, glucose levels and the insulin response to meal ingestion were also examined at these time points in glucagon receptor knockout mice (GCGR-/-) and their wildtype (wt) littermates. We found in normal mice that whereas the glucagon response to meal ingestion was not different between ZT3 and ZT15, the glucagon response to hypoglycemia was lower at ZT3 than at ZT15 and glucagon secretion from isolated islets was higher at ZT3 than at ZT15. GCGR-/- mice displayed lower basal glucose, a lower insulin response to meal and a higher insulin sensitivity than wt mice at ZT3 but not at ZT15. We conclude that there is a time dependent variation in glucagon secretion in normal mice, which is dependent both on intraislet and extraislet regulatory mechanisms and that the phenotype characteristics of a lower glucose and reduced insulin response to meal in GCGR-/- mice are evident only during the light phase. These findings suggest that glucagon signaling is a plausible contributor to the diurnal variation in glucose homeostasis which may explain that the phenotype of the GCGR-/- mice is dependent on the time of the day when it is examined. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Peptides
volume
76
pages
102 - 107
publisher
Elsevier
external identifiers
  • pmid:26774585
  • scopus:84955458612
  • wos:000369597900013
ISSN
1873-5169
DOI
10.1016/j.peptides.2016.01.008
language
English
LU publication?
yes
id
0708dc84-b85c-49c7-843c-2d0b015f8a2c (old id 8577472)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26774585?dopt=Abstract
date added to LUP
2016-02-03 17:23:11
date last changed
2017-01-01 07:29:47
@article{0708dc84-b85c-49c7-843c-2d0b015f8a2c,
  abstract     = {Glucose metabolism is subjected to diurnal variation, which might be mediated by alterations in the transcription pattern of clock genes and regulated by hormonal factors, as has been demonstrated for insulin. However, whether also glucagon is involved in the diurnal variation of glucose homeostasis is not known. We therefore examined glucagon secretion after meal ingestion (meal tolerance test) and during hypoglycemia (hyperinsulinemic hypoglycemic clamp at 2.5mmol/L glucose) and in vitro from isolated islets at ZT3 versus ZT15 in normal C57BL/6J mice and, furthermore, glucose levels and the insulin response to meal ingestion were also examined at these time points in glucagon receptor knockout mice (GCGR-/-) and their wildtype (wt) littermates. We found in normal mice that whereas the glucagon response to meal ingestion was not different between ZT3 and ZT15, the glucagon response to hypoglycemia was lower at ZT3 than at ZT15 and glucagon secretion from isolated islets was higher at ZT3 than at ZT15. GCGR-/- mice displayed lower basal glucose, a lower insulin response to meal and a higher insulin sensitivity than wt mice at ZT3 but not at ZT15. We conclude that there is a time dependent variation in glucagon secretion in normal mice, which is dependent both on intraislet and extraislet regulatory mechanisms and that the phenotype characteristics of a lower glucose and reduced insulin response to meal in GCGR-/- mice are evident only during the light phase. These findings suggest that glucagon signaling is a plausible contributor to the diurnal variation in glucose homeostasis which may explain that the phenotype of the GCGR-/- mice is dependent on the time of the day when it is examined.},
  author       = {Malmgren, Siri and Ahrén, Bo},
  issn         = {1873-5169},
  language     = {eng},
  pages        = {102--107},
  publisher    = {Elsevier},
  series       = {Peptides},
  title        = {Evidence for time dependent variation of glucagon secretion in mice.},
  url          = {http://dx.doi.org/10.1016/j.peptides.2016.01.008},
  volume       = {76},
  year         = {2016},
}