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Hyperglycaemia and reduced glucokinase expression in weanling offspring from dams maintained on a high-fat diet

Published online by Cambridge University Press:  08 March 2007

Marlon E. Cerf ,
Christo J. Muller ,
Don F. Du Toit ,
Johan Louw  and
Sonia A. Wolfe-Coote
Marlon E. Cerf*
Affiliation:
Diabetes Research Group, Medical Research Council, Tygerberg, South Africa Department of Anatomy and Histology, University of Stellenbosch, Tygerberg, South Africa
Christo J. Muller
Affiliation:
Department of Anatomy and Histology, University of Stellenbosch, Tygerberg, South Africa
Don F. Du Toit
Affiliation:
Department of Anatomy and Histology, University of Stellenbosch, Tygerberg, South Africa
Johan Louw
Affiliation:
Diabetes Research Group, Medical Research Council, Tygerberg, South Africa
Sonia A. Wolfe-Coote
Affiliation:
Diabetes Research Group, Medical Research Council, Tygerberg, South Africa
*
*corresponding author: Dr Marlon E. Cerf, fax +27 21 938 0456, email marlon.cerf@mrc.ac.za
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Abstract

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High-fat feeding reduces the expression of GLUT-2 and the glycolytic enzyme glucokinase (GK). The transcription factor, pancreatic duodenal homeobox-1 (Pdx-1), is important for β-cell maintenance. The aim of the present study was to determine, in weanling Wistar rats, the effect of a maternal high-fat diet (HFD) during defined periods of gestation and lactation, on body weight, circulating glucose and insulin concentrations, and the expression of GLUT-2, GK and Pdx-1. At postnatal day 21, weights were recorded and glucose and insulin concentrations were measured. The expression levels for mRNA were quantified by LightCycler PCR. Pancreatic sections, immunostained for GLUT-2, GK or Pdx-1, were assessed by image analysis. Weanlings from dams fed an HFD throughout gestation were lighter, with heavier weanlings produced from dams fed an HFD throughout gestation and lactation. Both these groups of weanlings were normoglycaemic, all the others being hyperglycaemic. Hypoinsulinaemia was evident in weanlings from dams fed an HFD throughout gestation only and also for either the first week of lactation or throughout lactation. GLUT-2 mRNA expression was reduced and GLUT-2 immunoreactivity was increased in most of the weanlings. GK mRNA expression and immunoreactivity was reduced in most of the offspring. Pdx-1 mRNA expression was increased in weanlings from dams fed an HFD throughout both gestation and lactation and reduced in those from dams only fed a lactational HFD. Normal Pdx-1 immunoreactivity was found in all of the weanlings. A maternal HFD induces hyperglycaemia in weanlings concomitant with reduced GK expression which may compromise β-cell function.

Keywords

Endocrine pancreasGlucose transporter-2HypoinsulinaemiaPancreatic duodenal homeobox-1Type 2 diabetes
Type
Research Article
Information
British Journal of Nutrition , Volume 95 , Issue 2 , February 2006 , pp. 391 - 396
Copyright
Copyright © The Nutrition Society 2006

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