Chronic administration of the glucagon-like peptide-1 analog, liraglutide, delays the onset of diabetes and lowers triglycerides in UCD-T2DM rats

Bethany P. Cummings, Kimber Stanhope, James L. Graham, Denis G. Baskin, Steven C. Griffen, Cecilia Nilsson, Anette Sams, Lotte B. Knudsen, Kirsten Raun, Peter J Havel

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43 Scopus citations

Abstract

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. RESEARCH DESIGN AND 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.

Original languageEnglish (US)
Pages (from-to)2653-2661
Number of pages9
JournalDiabetes
Volume59
Issue number10
DOIs
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Cummings, B. P., Stanhope, K., Graham, J. L., Baskin, D. G., Griffen, S. C., Nilsson, C., Sams, A., Knudsen, L. B., Raun, K., & Havel, P. J. (2010). Chronic administration of the glucagon-like peptide-1 analog, liraglutide, delays the onset of diabetes and lowers triglycerides in UCD-T2DM rats. Diabetes, 59(10), 2653-2661. https://doi.org/10.2337/db09-1564