title: Prophylactic effects of the glucagon-like Peptide-1 analog liraglutide on hyperglycemia in a rat model of type 2 diabetes mellitus associated with chronic pancreatitis and obesity.
abstract: The objective of this study was to investigate the effects of liraglutide, an analog of human glucagon-like peptide 1 (GLP1), on WBN/Kob-Lepr(fa) (fa/fa) rats, which spontaneously develop type 2 diabetes mellitus with pancreatic disorder and obesity. Male fa/fa rats (age, 7 wk) were allocated into 4 groups and received liraglutide (37.5, 75, 150 μg/kg SC) or saline (control group) once daily for 4 wk. All rats in the control group became overweight and developed hyperglycemia as they aged. Although the rats given liraglutide showed a dose-dependent reduction in food intake, no significant effects on body weight or fat content occurred. In the liraglutide groups, the development of hyperglycemia was suppressed, even as plasma insulin concentrations increased in a dose-dependent manner. Intravenous glucose tolerance testing of the liraglutide-treated rats confirmed improvement of glucose tolerance and enhanced insulin secretion. Histologic examination revealed increased numbers of pancreatic β-cell type islet cells and increased proliferation of epithelial cells of the small ducts in the liraglutide-treated groups. Although our study did not reveal a significant decrease in obesity after liraglutide administration, the results suggest a marked antidiabetic effect characterized by increased insulin secretion in fa/fa rats with pancreatic disorders.
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Nagakubo
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Shirai
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kaji
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Arisato
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Sena
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Takasugi
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan. asai@azabu-u.ac.jp.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Asai
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006943:Hyperglycemia / Q000209:etiology / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D000069450:Liraglutide; D008297:Male; D009765:Obesity / Q000150:complications*; D050500:Pancreatitis, Chronic / Q000150:complications* / Q000473:pathology; D065129:Pre-Exposure Prophylaxis / Q000379:methods; D051381:Rats
chemical_list: D007328:Insulin; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1