Altered beta-Cell Distribution of pdx-1 and GLUT-2 After a Short-Term Challenge With a High-Fat Diet in C57BL/6J Mice.
(2002) In Diabetes 51(Suppl 1). p.138-143- Abstract
- Mechanisms involved in the islet adaptation to insulin resistance were examined in mice of the C57BL/6J strain challenged with a high-fat (58%) diet for 8 weeks. Basal hyperglycemia commenced after 1 week, whereas hyperinsulinemia evolved after 8 weeks. Glucose elimination after an intravenous glucose challenge (1 g/kg) was significantly delayed after 1, 4, and 8 weeks on the high-fat diet compared with normal-diet--fed mice. This result was associated with unchanged insulin responses. However, glucose-stimulated insulin secretion from isolated islets was increased in a compensatory fashion at all glucose levels over a wide range (3.3--22 mmol/l) after 8 weeks on the high-fat diet, whereas no compensatory hypersecretion of insulin was... (More)
- Mechanisms involved in the islet adaptation to insulin resistance were examined in mice of the C57BL/6J strain challenged with a high-fat (58%) diet for 8 weeks. Basal hyperglycemia commenced after 1 week, whereas hyperinsulinemia evolved after 8 weeks. Glucose elimination after an intravenous glucose challenge (1 g/kg) was significantly delayed after 1, 4, and 8 weeks on the high-fat diet compared with normal-diet--fed mice. This result was associated with unchanged insulin responses. However, glucose-stimulated insulin secretion from isolated islets was increased in a compensatory fashion at all glucose levels over a wide range (3.3--22 mmol/l) after 8 weeks on the high-fat diet, whereas no compensatory hypersecretion of insulin was evident after 1 or 4 weeks, except at 22 mmol/l glucose. Immunohistochemistry revealed that the islet architecture of insulin and glucagon cells remained intact in islets from mice fed a high-fat diet. However, the nuclear translocation of the homeobox transcription factor, pdx-1, and the plasma membrane translocation of GLUT2 were both impaired in high-fat--fed animals after 1 week. In contrast, the expression of the full-length leptin receptor (ObRb) was not affected by high-fat feeding. The study thus shows that 8 weeks are required for the development of a compensatory hypersecretion of insulin after high-fat feeding in mice, and even then the in vivo insulin secretion is insufficient to normalize impaired glucose tolerance. The early-onset islet dysfunction is accompanied by impaired beta-cell trafficking of two factors, pdx-1 and GLUT-2, which are involved in beta-cell proliferation and glucose recognition. The mechanisms compromising this beta-cell trafficking remain to be established. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/106376
- author
- Kvist Reimer, Martina LU and Ahrén, Bo LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 51
- issue
- Suppl 1
- pages
- 138 - 143
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- pmid:11815473
- wos:000173599900025
- ISSN
- 1939-327X
- language
- English
- LU publication?
- yes
- id
- 843e564f-e20d-4798-a572-8d40ff48f829 (old id 106376)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11815473&dopt=Abstract
- http://diabetes.diabetesjournals.org/cgi/content/full/51/suppl_1/S138
- date added to LUP
- 2016-04-01 17:03:27
- date last changed
- 2023-04-18 19:19:33
@article{843e564f-e20d-4798-a572-8d40ff48f829,
abstract = {{Mechanisms involved in the islet adaptation to insulin resistance were examined in mice of the C57BL/6J strain challenged with a high-fat (58%) diet for 8 weeks. Basal hyperglycemia commenced after 1 week, whereas hyperinsulinemia evolved after 8 weeks. Glucose elimination after an intravenous glucose challenge (1 g/kg) was significantly delayed after 1, 4, and 8 weeks on the high-fat diet compared with normal-diet--fed mice. This result was associated with unchanged insulin responses. However, glucose-stimulated insulin secretion from isolated islets was increased in a compensatory fashion at all glucose levels over a wide range (3.3--22 mmol/l) after 8 weeks on the high-fat diet, whereas no compensatory hypersecretion of insulin was evident after 1 or 4 weeks, except at 22 mmol/l glucose. Immunohistochemistry revealed that the islet architecture of insulin and glucagon cells remained intact in islets from mice fed a high-fat diet. However, the nuclear translocation of the homeobox transcription factor, pdx-1, and the plasma membrane translocation of GLUT2 were both impaired in high-fat--fed animals after 1 week. In contrast, the expression of the full-length leptin receptor (ObRb) was not affected by high-fat feeding. The study thus shows that 8 weeks are required for the development of a compensatory hypersecretion of insulin after high-fat feeding in mice, and even then the in vivo insulin secretion is insufficient to normalize impaired glucose tolerance. The early-onset islet dysfunction is accompanied by impaired beta-cell trafficking of two factors, pdx-1 and GLUT-2, which are involved in beta-cell proliferation and glucose recognition. The mechanisms compromising this beta-cell trafficking remain to be established.}},
author = {{Kvist Reimer, Martina and Ahrén, Bo}},
issn = {{1939-327X}},
language = {{eng}},
number = {{Suppl 1}},
pages = {{138--143}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Altered beta-Cell Distribution of pdx-1 and GLUT-2 After a Short-Term Challenge With a High-Fat Diet in C57BL/6J Mice.}},
url = {{http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11815473&dopt=Abstract}},
volume = {{51}},
year = {{2002}},
}