Beta-Cell-Targeted Expression of a Dominant-Negative Mutant of Hepatocyte Nuclear Factor-1{alpha} in Mice: Diabetes Model with {beta}-Cell Dysfunction Partially Rescued by Nonglucose Secretagogues.
(2004) In Diabetes 53(suppl_3). p.92-96- Abstract
- We studied islet function in mice with beta-cell-targeted expression of a dominant-negative mutant of hepatocyte nuclear factor (HNF)-1alpha. At age 2-3 months, anesthetized transgenic and wild-type male mice underwent an intravenous glucose (1 g/kg) tolerance test (IVGTT). It was found that transgenic mice had an abolished insulin response in association with severe glucose intolerance. In other tests, the 5-min insulin response to intravenous arginine was impaired by 79% (P=0.032) and the 15-min insulin response to gastric glucose was suppressed by 97% (P=0.006). In islets incubated for 60 min, the insulin response to glucose (3.3-22.2 mmol/l) was impaired by >80% in transgenic mice. In contrast, insulin responses to nonglucose... (More)
- We studied islet function in mice with beta-cell-targeted expression of a dominant-negative mutant of hepatocyte nuclear factor (HNF)-1alpha. At age 2-3 months, anesthetized transgenic and wild-type male mice underwent an intravenous glucose (1 g/kg) tolerance test (IVGTT). It was found that transgenic mice had an abolished insulin response in association with severe glucose intolerance. In other tests, the 5-min insulin response to intravenous arginine was impaired by 79% (P=0.032) and the 15-min insulin response to gastric glucose was suppressed by 97% (P=0.006). In islets incubated for 60 min, the insulin response to glucose (3.3-22.2 mmol/l) was impaired by >80% in transgenic mice. In contrast, insulin responses to nonglucose secretagogues were only partially suppressed (to GLP-1 [100 nmol/l] by 40%, to carbachol [1 micromol/l] by 20%, and to palmitate [0.5 mmol/l] by 15%), whereas the response to depolarization by KCl (50 mmol/l) was not reduced. Finally, the IVGTT data insulin sensitivity in transgenic mice was not significantly different from that of wild-type mice. Thus, mice with targeted suppression of beta-cell HNF-1alpha represent a good diabetes model exhibiting severely impaired insulin secretion after glucose with marked glucose intolerance. In contrast, the insulin responses to nonglucose stimuli are not suppressed when the islet insulin content is taken into account. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/130676
- author
- Sörhede Winzell, Maria LU ; Ahrén, Bo LU ; Wollheim, Claes B. and Pacini, Giovanni
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 53
- issue
- suppl_3
- pages
- 92 - 96
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- wos:000225460000015
- scopus:9444219603
- ISSN
- 1939-327X
- DOI
- 10.2337/diabetes.53.suppl_3.S92
- language
- English
- LU publication?
- yes
- id
- 09f11490-d165-41ca-a505-4a4dfa3f019c (old id 130676)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15561929&dopt=Abstract
- date added to LUP
- 2016-04-01 16:12:20
- date last changed
- 2024-03-25 05:13:43
@article{09f11490-d165-41ca-a505-4a4dfa3f019c,
abstract = {{We studied islet function in mice with beta-cell-targeted expression of a dominant-negative mutant of hepatocyte nuclear factor (HNF)-1alpha. At age 2-3 months, anesthetized transgenic and wild-type male mice underwent an intravenous glucose (1 g/kg) tolerance test (IVGTT). It was found that transgenic mice had an abolished insulin response in association with severe glucose intolerance. In other tests, the 5-min insulin response to intravenous arginine was impaired by 79% (P=0.032) and the 15-min insulin response to gastric glucose was suppressed by 97% (P=0.006). In islets incubated for 60 min, the insulin response to glucose (3.3-22.2 mmol/l) was impaired by >80% in transgenic mice. In contrast, insulin responses to nonglucose secretagogues were only partially suppressed (to GLP-1 [100 nmol/l] by 40%, to carbachol [1 micromol/l] by 20%, and to palmitate [0.5 mmol/l] by 15%), whereas the response to depolarization by KCl (50 mmol/l) was not reduced. Finally, the IVGTT data insulin sensitivity in transgenic mice was not significantly different from that of wild-type mice. Thus, mice with targeted suppression of beta-cell HNF-1alpha represent a good diabetes model exhibiting severely impaired insulin secretion after glucose with marked glucose intolerance. In contrast, the insulin responses to nonglucose stimuli are not suppressed when the islet insulin content is taken into account.}},
author = {{Sörhede Winzell, Maria and Ahrén, Bo and Wollheim, Claes B. and Pacini, Giovanni}},
issn = {{1939-327X}},
language = {{eng}},
number = {{suppl_3}},
pages = {{92--96}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Beta-Cell-Targeted Expression of a Dominant-Negative Mutant of Hepatocyte Nuclear Factor-1{alpha} in Mice: Diabetes Model with {beta}-Cell Dysfunction Partially Rescued by Nonglucose Secretagogues.}},
url = {{http://dx.doi.org/10.2337/diabetes.53.suppl_3.S92}},
doi = {{10.2337/diabetes.53.suppl_3.S92}},
volume = {{53}},
year = {{2004}},
}