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Impact of glucose dosing regimens on modeling of glucose tolerance and β-cell function by intravenous glucose tolerance test in diet-induced obese mice.

Omar, Bilal LU ; Pacini, Giovanni and Ahrén, Bo LU (2014) In Physiological Reports 2(5).
Abstract
Insulin sensitivity declines in overweight and obese individuals and, under normal conditions, insulin secretion adaptively increases which in healthy non-diabetic subjects maintains normal glycemia. This adaptation is best described by the disposition index derived from modeling of insulin and glucose data from an intravenous glucose tolerance testing (IVGTT). One caveat of the IVGTT is that basing the glucose dose on the individual total body weight can result in large differences in the amount of glucose given to lean and obese individuals. The effect this has on determination of insulin sensitivity and β-cell function is unknown. In this study, we therefore evaluated alternative glucose dosing regimens for determination of the impact... (More)
Insulin sensitivity declines in overweight and obese individuals and, under normal conditions, insulin secretion adaptively increases which in healthy non-diabetic subjects maintains normal glycemia. This adaptation is best described by the disposition index derived from modeling of insulin and glucose data from an intravenous glucose tolerance testing (IVGTT). One caveat of the IVGTT is that basing the glucose dose on the individual total body weight can result in large differences in the amount of glucose given to lean and obese individuals. The effect this has on determination of insulin sensitivity and β-cell function is unknown. In this study, we therefore evaluated alternative glucose dosing regimens for determination of the impact of glucose dosing on measures of β-cell function in normal and diet-induced obese (DIO) mice. The glucose dosing regimens used for the IVGTT were 0.35 mg per kg total body weight (BW) or per kg lean BW or a fixed glucose dose based on the average BW for all experimental mice. Each regimen detected a similar decrease in insulin sensitivity in DIO mice. The different glucose dosing regimens gave, however, diverging results in regard to glucose elimination and the acute insulin response. Thus, the fixed-dose regimen was the only that revealed impairment of glucose elimination, whereas dosing according to total BW was the only regimen which showed significant increases in acute insulin response in DIO mice. The fixed-dose glucose dosing regimen was the only that revealed a significant decline in the disposition index value in DIO mice, which is characteristic of type 2 diabetes in humans. Our results therefore show that using different glucose dosing regimens during IVGTT in DIO mice one can model different aspects of physiology which are similar to prediabetes and type 2 diabetes in humans, with the fixed-dose regimen producing a phenotype that most closely resembles human type 2 diabetes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physiological Reports
volume
2
issue
5
publisher
John Wiley & Sons
external identifiers
  • pmid:24843074
  • scopus:85002791386
ISSN
2051-817X
DOI
10.14814/phy2.12011
language
English
LU publication?
yes
id
763d2f18-bf28-434b-9700-7902172b2570 (old id 4454110)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24843074?dopt=Abstract
date added to LUP
2014-06-04 22:02:49
date last changed
2017-06-18 03:58:46
@article{763d2f18-bf28-434b-9700-7902172b2570,
  abstract     = {Insulin sensitivity declines in overweight and obese individuals and, under normal conditions, insulin secretion adaptively increases which in healthy non-diabetic subjects maintains normal glycemia. This adaptation is best described by the disposition index derived from modeling of insulin and glucose data from an intravenous glucose tolerance testing (IVGTT). One caveat of the IVGTT is that basing the glucose dose on the individual total body weight can result in large differences in the amount of glucose given to lean and obese individuals. The effect this has on determination of insulin sensitivity and β-cell function is unknown. In this study, we therefore evaluated alternative glucose dosing regimens for determination of the impact of glucose dosing on measures of β-cell function in normal and diet-induced obese (DIO) mice. The glucose dosing regimens used for the IVGTT were 0.35 mg per kg total body weight (BW) or per kg lean BW or a fixed glucose dose based on the average BW for all experimental mice. Each regimen detected a similar decrease in insulin sensitivity in DIO mice. The different glucose dosing regimens gave, however, diverging results in regard to glucose elimination and the acute insulin response. Thus, the fixed-dose regimen was the only that revealed impairment of glucose elimination, whereas dosing according to total BW was the only regimen which showed significant increases in acute insulin response in DIO mice. The fixed-dose glucose dosing regimen was the only that revealed a significant decline in the disposition index value in DIO mice, which is characteristic of type 2 diabetes in humans. Our results therefore show that using different glucose dosing regimens during IVGTT in DIO mice one can model different aspects of physiology which are similar to prediabetes and type 2 diabetes in humans, with the fixed-dose regimen producing a phenotype that most closely resembles human type 2 diabetes.},
  author       = {Omar, Bilal and Pacini, Giovanni and Ahrén, Bo},
  issn         = {2051-817X},
  language     = {eng},
  number       = {5},
  publisher    = {John Wiley & Sons},
  series       = {Physiological Reports},
  title        = {Impact of glucose dosing regimens on modeling of glucose tolerance and β-cell function by intravenous glucose tolerance test in diet-induced obese mice.},
  url          = {http://dx.doi.org/10.14814/phy2.12011},
  volume       = {2},
  year         = {2014},
}