Peripubertal hyperinsulinemia upregulates phosphatidylinositol 3-kinase/akt pathway in rat ovaries.
OBJECTIVE
Polycystic ovary syndrome (PCOS) usually develops during peripuberty and is often associated with hyperinsulinemia. Paradoxically, hyperinsulinemic patients with PCOS develop peripheral insulin resistance but retain ovarian insulin sensitivity. We investigated the effect of peripubertal hyperinsulinemia on insulin signaling pathways in rat ovaries.


METHODS
Hyperinsulinemia was induced in peripubertal female rats by infusing insulin (0.14 IU/day) for 4 weeks. Control animals received normal saline. At autopsy, trunk blood was collected for insulin assay; ovaries were collected for examining the effect of hyperinsulinemia on phosphatidylinositol 3-kinase/Akt (PI3-K/Akt) and mitogen-activated protein kinase (MAPK/ERK1/2) pathways.


RESULTS
Compared with control, ovarian protein levels of total Akt, phospho-Akt, and phospho-glycogen synthase kinase-3beta were upregulated and phospho-phosphatase and tensin homolog was downregulated in hyperinsulinemic animals. The MAPK/ERK1/2 pathway was unaffected.


CONCLUSIONS
Peripubertal hyperinsulinemia upregulates the PI3-K/Akt pathway in rat ovaries. Ovarian insulin sensitivity in hyperinsulinemic patients with PCOS is potentially retained by this mechanism.
Chakrabarty
Shilla
S
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555, USA. schakrab@utmb.edu
Nagamani
Manubai
M
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006946:Hyperinsulinism / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007328:Insulin; D008840:Microfilament Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010053:Ovary / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation; D015398:Signal Transduction; D000070876:Tensins; D015854:Up-Regulation
D007328:Insulin; D008840:Microfilament Proteins; D000070876:Tensins; C000603372:Tns1 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3