title: Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle.
abstract: Data derived principally from peripheral tissues (fat, muscle and liver) show that insulin signals via diverse interconnecting intracellular pathways and that some of the major intersecting points (known as critical nodes) are the IRSs (insulin receptor substrates), PI3K (phosphoinositide kinase)/Akt and MAPK (mitogen-activated protein kinase). Most of these insulin pathways are probably also active in the ovary and their ability to interact with each other and also with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) signalling pathways enables insulin to exert direct modulating influences on ovarian function. The present paper reviews the intracellular actions of insulin and the uptake of glucose by ovarian tissues (granulosa, theca and oocyte) during the oestrous/menstrual cycle of some rodent, primate and ruminant species. Insulin signals through diverse pathways and these are discussed with specific reference to follicular cell types (granulosa, theca and oocyte). The signalling pathways for FSH in granulosa cells and LH in granulosa and theca cells are summarized. The roles of glucose and of insulin-mediated uptake of glucose in folliculogenesis are discussed. It is suggested that glucose in addition to its well-established role of providing energy for cellular function may also have insulin-mediated signalling functions in ovarian cells, involving AMPK (AMP-dependent protein kinase) and/or hexosamine. Potential interactions of insulin signalling with FSH or LH signalling at critical nodes are identified and the available evidence for such interactions in ovarian cells is discussed. Finally the action of the insulin-sensitizing drugs metformin and the thiazolidinedione rosiglitazone on follicular cells is reviewed.
authors.affiliation: UMR 7247 Physiologie de la Reproduction et des Comportements, CNRS, INRA, Université de Tours, Institut Français du Cheval et de l'Équitation, 37380 Nouzilly, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dupont
authors.affiliation: UMR 7247 Physiologie de la Reproduction et des Comportements, CNRS, INRA, Université de Tours, Institut Français du Cheval et de l'Équitation, 37380 Nouzilly, France Department of Comparative Biological Sciences, Royal Veterinary College, Hawkshead Lane, South Mimms, Hertfordshire AL9 7TA, U.K. rex.scaramuzzi@orange.fr.
authors.forename: Rex J
authors.initials: RJ
authors.lastname: Scaramuzzi
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D008597:Menstrual Cycle / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose
keywords: Akt; MAPK; corpus luteum; follicle-stimulating hormone (FSH); granulosa; insulin receptor substrate (IRS); luteinizing hormone (LH); metformin; oestradiol; oocyte; progesterone; theca; thiazolidinedione