Increased cell proliferation and contractility of prostate in insulin resistant rats: linking hyperinsulinemia with benign prostate hyperplasia.
BACKGROUND
Obesity, dyslipidemia, Hyperinsulinemia, and insulin resistance (IR) are key features of metabolic syndrome and are considered as risk factors for benign prostatic hyperplasia (BPH) as well as type 2 diabetes. The present study was aimed to determine whether or not IR associated hyperinsulinemia contributes to the BPH.


METHODS
Sprague-Dawley rats (9 weeks) were used in the study. Rats were kept on high fat diet (HFD) for the induction of hyperinsulinemia while hypoinsulinemia was induced by streptozotocin. Effect of HFD feeding on the testosterone-induced prostatic growth was evaluated. Pioglitazone (PG, 20 mg/kg) was used for the reversal of compensatory hyperinsulinemia and to examine the subsequent effect on the prostatic growth.


RESULTS
Prostatic enlargement was observed in the HFD-fed rats. Significant increase in the cell proliferation markers confirmed the occurrence of cellular hyperplasia in the prostate of hyperinsulinemic rat. Enhanced alpha-adrenoceptor mediated contraction in the prostate of HFD-fed rats indicates augmented contractility of the gland. Higher level of phosphorylated-ERK suggests enhanced MEK/ERK signaling. HFD feeding has not led to change in the plasma testosterone level. However, testosterone treatment further augmented the prostatic growth in HFD-fed rats. PG treatment led to improved insulin sensitivity, decreased plasma insulin level and prostate weight, indicating the role of compensatory hyperinsulinemia in the prostate growth.


CONCLUSIONS
The present investigation reports that HFD-feeding induced hyperinsulinemic condition leads to increased cellular proliferation, enhanced alpha-adrenoceptor mediated contraction, and enlargement of the prostate in rats.
Vikram
A
A
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India.
Jena
G B
GB
Ramarao
P
P
D000818:Animals; D049109:Cell Proliferation; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D006946:Hyperinsulinism / Q000150:complications* / Q000473:pathology*; D007333:Insulin Resistance; D008297:Male; D011467:Prostate / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000209:etiology* / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D004041:Dietary Fats