Document Detail


Rosiglitazone aggravates nonalcoholic Fatty pancreatic disease in C57BL/6 mice fed high-fat and high-sucrose diet.
MedLine Citation:
PMID:  19214135     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Evaluate the effect of fenofibrate, bezafibrate, and rosiglitazone on nonalcoholic fatty pancreatic disease and islet peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-beta immunostain in mice fed high-fat high-sucrose (HFHS) diet. METHODS: Two-month-old male mice were fed standard chow (n = 10) or HFHS chow (n = 40) for 6 weeks. Afterward, HFHS mice were grouped by treatment: untreated HFHS and HFHS treated with rosiglitazone (HFHS-Ro), fenofibrate (HFHS-Fe), or bezafibrate (HFHS-Bz). Medications were administered for 5 weeks. After treatment, the pancreas was removed and analyzed by morphometry, stereology, and immunohistochemistry. RESULTS: The HFHS-fed mice showed altered fasting glucose (+33%) and insulin (+138%); increased body (+20%) and pancreas (+28%) masses, pancreatic fat (+700%), islet hypertrophy (+38%); and decreased GLUT2 immunostain (-60%). Rosiglitazone reduced fasting glucose and insulin but induced weight gain. Fibrates impeded weight gain, but only bezafibrate prevented islet hypertrophy. The GLUT2 stain was improved in all treatments, and there were no alterations in PPAR-alpha. There were morphological signs of pancreatitis with fenofibrate, although there were no alterations in amylase and lipase. Rosiglitazone exacerbated pancreatic fat infiltration (+75% vs HFHS group), and bezafibrate increased PPAR-beta expression in pancreatic islets. CONCLUSIONS: Rosiglitazone is shown for the first time to exacerbate pancreatic fat infiltration; therefore, precaution has to be taken when rosiglitazone is prescribed to obese patients.
Authors:
Caroline Fernandes-Santos; Rafael Evangelista Carneiro; Leonardo de Souza Mendonca; Márcia Barbosa Aguila; Carlos Alberto Mandarim-de-Lacerda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pancreas     Volume:  38     ISSN:  1536-4828     ISO Abbreviation:  Pancreas     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-25     Completed Date:  2009-05-18     Revised Date:  2009-09-03    
Medline Journal Info:
Nlm Unique ID:  8608542     Medline TA:  Pancreas     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e80-6     Citation Subset:  IM    
Affiliation:
Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / pathology
Animals
Antilipemic Agents / pharmacology
Bezafibrate / pharmacology
Blood Glucose / metabolism
Diabetes Mellitus, Type 2 / drug therapy
Dietary Fats / pharmacology*
Dietary Sucrose / pharmacology*
Energy Metabolism / drug effects
Hypoglycemic Agents / toxicity*
Insulin / blood
Male
Mice
Mice, Inbred C57BL
Obesity / drug therapy
PPAR alpha / metabolism
PPAR-beta / metabolism
Pancreatic Diseases / chemically induced*,  metabolism,  pathology
Procetofen / pharmacology
Thiazolidinediones / toxicity*
Weight Gain / drug effects
Chemical
Reg. No./Substance:
0/Antilipemic Agents; 0/Blood Glucose; 0/Dietary Fats; 0/Dietary Sucrose; 0/Hypoglycemic Agents; 0/PPAR alpha; 0/PPAR-beta; 0/Thiazolidinediones; 11061-68-0/Insulin; 122320-73-4/rosiglitazone; 41859-67-0/Bezafibrate; 49562-28-9/Procetofen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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