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Åke Lernmark

Principal investigator

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Increased Lipid Oxidation Heralds Diabetes Onset in DR.lyp/lyp Rats.

Author

  • Lina Åkesson
  • R Gelling
  • R Jensen
  • K Ogimoto
  • J Fuller
  • R Pefley
  • S Manavi
  • Åke Lernmark
  • M Schwartz

Summary, in English

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, VO (2), VCO (2) 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.

Department/s

  • Diabetes and Celiac Unit

Publishing year

2008

Language

English

Pages

475-480

Publication/Series

Experimental and Clinical Endocrinology & Diabetes

Volume

116

Document type

Journal article

Publisher

Georg Thieme Verlag KG

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 1439-3646