Chronic administration of the glucagon-like peptide-1 analog, liraglutide, delays the onset of diabetes and lowers triglycerides in UCD-T2DM rats.
OBJECTIVE
The efficacy of liraglutide, a human glucagon-like peptide-1 (GLP-1) analog, to prevent or delay diabetes in UCD-T2DM rats, a model of polygenic obese type 2 diabetes, was investigated.


METHODS
At 2 months of age, male rats were divided into three groups: control, food-restricted, and liraglutide. Animals received liraglutide (0.2 mg/kg s.c.) or vehicle injections twice daily. Restricted rats were food restricted to equalize body weights to liraglutide-treated rats. Half of the animals were followed until diabetes onset, whereas the other half of the animals were killed at 6.5 months of age for tissue collection.


RESULTS
Before diabetes onset energy intake, body weight, adiposity, and liver triglyceride content were higher in control animals compared with restricted and liraglutide-treated rats. Energy-restricted animals had lower food intake than liraglutide-treated animals to maintain the same body weights, suggesting that liraglutide increases energy expenditure. Liraglutide treatment delayed diabetes onset by 4.1 ± 0.8 months compared with control (P < 0.0001) and by 1.3 ± 0.8 months compared with restricted animals (P < 0.05). Up to 6 months of age, energy restriction and liraglutide treatment lowered fasting plasma glucose and A1C concentrations compared with control animals. In contrast, liraglutide-treated animals exhibited lower fasting plasma insulin, glucagon, and triglycerides compared with both control and restricted animals. Furthermore, energy-restricted and liraglutide-treated animals exhibited more normal islet morphology.


CONCLUSIONS
Liraglutide treatment delays the development of diabetes in UCD-T2DM rats by reducing energy intake and body weight, and by improving insulin sensitivity, improving lipid profiles, and maintaining islet morphology.
Cummings
Bethany P
BP
Department of Molecular Biosciences, School of Veterinary Medicine,University of California, Davis, Davis, California, USA.
Stanhope
Kimber L
KL
Graham
James L
JL
Baskin
Denis G
DG
Griffen
Steven C
SC
Nilsson
Cecilia
C
Sams
Anette
A
Knudsen
Lotte B
LB
Raun
Kirsten
K
Havel
Peter J
PJ
D017668:Age of Onset; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D004231:Diuresis / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D000069450:Liraglutide; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D051381:Rats; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D000069450:Liraglutide; D014280:Triglycerides