Journal article
Pioglitazone attenuates prostatic enlargement in diet-induced insulin-resistant rats by altering lipid distribution and hyperinsulinaemia
British journal of pharmacology, Vol.161(8), pp.1708-1721
12/01/2010
DOI: 10.1111/j.1476-5381.2010.00994.x
PMCID: PMC3010577
PMID: 20726985
Abstract
BACKGROUND AND PURPOSE
Increased incidence of benign prostatic hyperplasia among insulin-resistant individuals suggests a role for hyperinsulinaemia in prostatic enlargement. We have already reported increased cell proliferation and enlargement of prostate gland in insulin-resistant rats. The present study aimed to elucidate the molecular mechanisms underlying the reversal of prostatic enlargement in insulin-resistant rats by the peroxisome proliferator-activated receptor gamma agonist pioglitazone.
EXPERIMENTAL APPROACH
Sprague-Dawley rats were fed a normal pellet or a high-fat diet for 12 weeks with or without pioglitazone (20 mg.kg(-1)). Subgroups of animals fed different diets were castrated. Effects of dietary manipulation and pioglitazone were measured on insulin sensitivity, lipid distribution, cell proliferation and apoptosis.
KEY RESULTS
A high-fat diet led to the accumulation of fat in non-adipose tissues, insulin resistance, compensatory hyperinsulinaemia and prostatic enlargement in rats. Pioglitazone treatment altered fat distribution, improved insulin sensitivity and normalized lipid and insulin level in rats on the high-fat diet. The improved metabolic parameters led to decreased cellular proliferation and increased apoptosis in the prostate gland. High-fat diet feeding and pioglitazone treatment did not change plasma testosterone levels. However, significant prostatic atrophy was observed in castrated rats irrespective of dietary intervention.
CONCLUSIONS AND IMPLICATIONS
Our results show a previously unexplored therapeutic potential of pioglitazone for prostatic enlargement under insulin-resistant condition and further suggest that targeting distribution of lipid from non-adipose tissue to adipose tissue and insulin signalling could be new strategies for the treatment of benign prostatic hyperplasia.
Details
- Title: Subtitle
- Pioglitazone attenuates prostatic enlargement in diet-induced insulin-resistant rats by altering lipid distribution and hyperinsulinaemia
- Creators
- Ajit Vikram - National Institute of Pharmaceutical Education and ResearchGopabandhu Jena - National Institute of Pharmaceutical Education and ResearchPoduri Ramarao - National Institute of Pharmaceutical Education and Research
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.161(8), pp.1708-1721
- DOI
- 10.1111/j.1476-5381.2010.00994.x
- PMID
- 20726985
- PMCID
- PMC3010577
- NLM abbreviation
- Br J Pharmacol
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Publisher
- Wiley
- Number of pages
- 14
- Grant note
- National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, India
- Language
- English
- Date published
- 12/01/2010
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984359767402771
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