RGD Reference Report - Increased Lipid Oxidation Heralds Diabetes Onset in DR.lyp/lyp Rats. - Rat Genome Database

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

Authors: Akesson, L  Gelling, RW  Jensen, R  Ogimoto, K  Fuller, JM  Pefley, R  Manavi, S  Lernmark, A  Schwartz, MW 
Citation: Akesson L, etal., Exp Clin Endocrinol Diabetes. 2008 May 9;.
RGD ID: 2293508
Pubmed: PMID:18465680   (View Abstract at PubMed)
DOI: DOI:10.1055/s-2008-1062713   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BBDR.BBDP-(D4Mit6-D4Mit7)/1RhwRathyperglycemia onsetIAGP  RGD 
BBDR.BBDP-(D4Mit6-D4Mit7)/1RhwRattype 1 diabetes mellitus onsetIAGP compared to DR.lyp/+RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gimap5Ratnegative regulation of lipid catabolic process  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BBDR.BBDP-(D4Mit6-D4Mit7)/1RhwRatabnormal respiratory quotient  IAGP compared to DR.lyp/+RGD 
BBDR.BBDP-(D4Mit6-D4Mit7)/1RhwRatincreased susceptibility to autoimmune diabetes  IAGP compared to DR.lyp/+RGD 
Objects Annotated

Genes (Rattus norvegicus)
Gimap5  (GTPase, IMAP family member 5)

Objects referenced in this article
Strain BBDR.BBDP-(D4Mit6-D4Mit7)/2Rhw null Rattus norvegicus
Strain BBDR.BBDP-(D4Mit6-D4Mit7)/3Rhw null Rattus norvegicus

Additional Information