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DOI: 10.1055/s-2008-1062713
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Increased Lipid Oxidation Heralds Diabetes Onset in DR.lyp/lyp Rats
Publication History
received 25.10.2007
first decision 11.02.2008
accepted 11.02.2008
Publication Date:
09 May 2008 (online)
Abstract
Aim: The BB rat model of type 1 diabetes exhibits altered body weight gain and body temperature regulation prior to hyperglycemia onset, implying the existence of as yet unidentified biomarkers of autoimmune processes that destroy pancreatic beta cells. To investigate this hypothesis, we compared the metabolic profile of diabetes-resistant DR.lyp/+ rats and their diabetes-prone, congenic DR.lyp/lyp littermates in the days leading up to diabetes onset.
Methods: Except for the Gimap5 mutation on chromosome 4, congenic DR.lyp/lyp rats are genetically identical to DR.lyp/+ littermates. They invariably develop hyperglycemia at 46–81 days of age, whereas DR.lyp/+ rats do not develop diabetes. In addition to daily food intake and body weight, indirect calorimetry was performed continuously on male DR.lyp/lyp and DR.lyp/+ rats (n=6/group) for 6–18 days to measure locomotor activity, VO2, VCO2 and RQ.
Results: DR.lyp/lyp rats exhibited a progressive decrease of RQ compared to DR.lyp/+ rats 0.005±0.001 units/day (p<0.005). Limiting the analysis to the six days prior to diabetes onset revealed a larger decrease of 0.007±0.002 units/day (p<0.001) in DR.lyp/lyp animals, whereas RQ of the DR.lyp/+ rats remained unchanged. This metabolic change occurred prior to hyperglycemia onset and was not associated with changes of any other parameter.
Conclusions: Diabetes onset in DR.lyp/lyp rats is heralded by a progressive shift towards lipid oxidation relative to carbohydrate metabolism.
Key words
pre-diabetes - metabolism - biomarker - prediction of type 1 diabetes
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1 These authors contributed equally to this article.
Correspondence
Dr. L. Âkesson
Lund University/CRC
Department of Clinical Sciences
Ing 72, Bldg 91:10
University Hospital MAS
20502 Malmö
Phone: +46/40/39 19 03
Fax: +46/40/39 19 19
Email: Lina.akesson@med.lu.se