The prostacyclin analog beraprost sodium ameliorates characteristics of metabolic syndrome in obese Zucker (fatty) rats.
OBJECTIVE
The prostacyclin analog, beraprost sodium (BPS), was examined for its potential to improve the symptoms of obesity-type diabetes (i.e., hyperglycemia, hyperinsulinemia, dyslipidemia, histopathologic changes, and diabetic complications).


METHODS
Obese Zucker rats, an experimental model of genetic obesity-induced type 2 diabetes, were repeatedly administered BPS at oral doses of 0.2 or 0.6 mg x kg(-1) x day(-1) b.i.d. for 12 weeks, and serum chemistry, urinalysis, and histopathologic examination were performed.


RESULTS
BPS dose-dependently suppressed serum glucose, insulin, triglyceride, and cholesterol levels in obese animals. In oral glucose tolerance test, BPS suppressed the post-glucose-loading elevation of serum glucose in a dose-dependent manner. Urinary N-acetyl-beta-D-glucosaminidase was significantly lower in BPS-treated obese animals compared with control animals, although no significant differences were observed in urinary protein levels between the BPS-treated groups and the control group. In addition, histopathologic examination revealed significant protective effects of BPS against renal disorder in obese animals. Histopathologically, BPS also inhibited the progression of hepatic steatosis, hypertrophy of adipose tissue, and pancreatic fibrosis. Furthermore, thermographic analysis of the hind limb sole skin surface indicated a significant increase in temperature in BPS-treated animals, compared with control animals, which was likely due to improved blood circulation by administration of BPS.


CONCLUSIONS
BPS suppressed the pathogenesis and development of diabetes and its complication, nephropathy, which was presumably accompanied by improving glucose intolerance and insulin resistance in obese Zucker rats.
Sato
Nahoko
N
The First Pharmacology Laboratory, Pharmaceutical Research Labs, Toray Industries, Kamakura, Kanagawa, Japan. nahoko_sato@nts.toray.co.jp
Kaneko
Masayuki
M
Tamura
Mitsutaka
M
Kurumatani
Hajimu
H
D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003451:Cryoprotective Agents / Q000627:therapeutic use*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009765:Obesity / Q000150:complications*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker; D012881:Skin Temperature / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002784:Cholesterol; D003451:Cryoprotective Agents; D011464:Epoprostenol; D006442:Glycated Hemoglobin; D007328:Insulin; D014280:Triglycerides; C048081:beraprost