Abstract |
Although peroxisome proliferator-activated receptor ( PPAR)gamma agonists ameliorate insulin resistance, they sometimes cause body weight gain, and the effect of PPAR agonists on insulin secretion is unclear. We evaluated the effects of combination therapy with a PPARgamma agonist, pioglitazone, and a PPARalpha agonist, bezafibrate, and a dual agonist, KRP-297, for 4 wk in male C57BL/6J mice and db/db mice, and we investigated glucose-stimulated insulin secretion (GSIS) by in situ pancreatic perfusion. Body weight gain in db/db mice was less with KRP-297 treatment than with pioglitazone or pioglitazone + bezafibrate treatment. Plasma glucose, insulin, triglyceride, and nonesterified fatty acid levels were elevated in untreated db/db mice compared with untreated C57BL/6J mice, and these parameters were significantly ameliorated in the PPARgamma agonist-treated groups. Also, PPARgamma agonists ameliorated the diminished GSIS and insulin content, and they preserved insulin and GLUT2 staining in db/db mice. GSIS was further increased by PPARgamma and -alpha agonists. We conclude that combination therapy with PPARgamma and PPARalpha agonists may be more useful with respect to body weight and pancreatic GSIS in type 2 diabetes with obesity.
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Authors | Ken Yajima, Hiroshi Hirose, Haruhisa Fujita, Yoshiko Seto, Hiroshi Fujita, Kaname Ukeda, Kiichi Miyashita, Toshihide Kawai, Yukihiro Yamamoto, Takeo Ogawa, Taketo Yamada, Takao Saruta |
Journal | American journal of physiology. Endocrinology and metabolism
(Am J Physiol Endocrinol Metab)
Vol. 284
Issue 5
Pg. E966-71
(May 2003)
ISSN: 0193-1849 [Print] United States |
PMID | 12676649
(Publication Type: Journal Article)
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Chemical References |
- Glucose Transporter Type 2
- Insulin
- Monosaccharide Transport Proteins
- Receptors, Cytoplasmic and Nuclear
- Thiazoles
- Thiazolidinediones
- Thiazolidines
- Transcription Factors
- 5-((2,4-dioxo-5-thiazolidinyl)methyl)-2-methoxy-N-((4-(trifluoromethyl)phenyl)methyl)benzamide
- Glucose
- Pioglitazone
- Bezafibrate
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Topics |
- Animals
- Bezafibrate
(pharmacology)
- Body Weight
- Diabetes Mellitus
(blood, genetics, metabolism, pathology)
- Drug Therapy, Combination
- Glucose
(pharmacology)
- Glucose Transporter Type 2
- Insulin
(metabolism)
- Insulin Secretion
- Islets of Langerhans
(metabolism, pathology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Mutant Strains
- Monosaccharide Transport Proteins
(metabolism)
- Pancreas
(metabolism)
- Pioglitazone
- Receptors, Cytoplasmic and Nuclear
(agonists)
- Thiazoles
(pharmacology)
- Thiazolidinediones
- Thiazolidines
- Transcription Factors
(agonists)
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