Abstract
BackgroundInsulin and its plasma membrane receptor constitute an ancient response system critical to cell growth and differentiation. Studies using intact Rana pipiens oocytes have shown that insulin can act at receptors on the oocyte surface to initiate resumption of the first meiotic division. We have reexamined the insulin-induced cascade of electrical and ion transport-related plasma membrane events using both oocytes and intact plasma membranes in order to characterize the insulin receptor-steroid response system associated with the meiotic divisions.Results[125I]Insulin binding (Kd = 54 ± 6 nM) at the oocyte plasma membrane activates membrane serine protease(s), followed by the loss of low affinity ouabain binding sites, with a concomitant 3–4 fold increase in high affinity ouabain binding sites. The changes in protease activity and ouabain binding are associated with increased Na+/Ca2+ exchange, increased endocytosis, decreased Na+ conductance resulting in membrane hyperpolarization, increased 2-deoxy-D-glucose uptake and a sustained elevation of intracellular pH (pHi). Hyperpolarization is largely due to Na+-channel inactivation and is the main driving force for glucose uptake by the oocyte via Na+/glucose cotransport. The Na+ sym- and antiporter systems are driven by the Na+ free energy gradient generated by Na+/K+-ATPase. Shifts in α and/or β Na+-pump subunits to caveolar (lipid raft) membrane regions may activate Na/K-ATPase and contribute to the Na+ free energy gradient and the increase in both Na+/glucose co-transport and pHi.ConclusionsUnder physiological conditions, resumption of meiosis results from the concerted action of insulin and progesterone at the cell membrane. Insulin inactivates Na+ channels and mobilizes fully functional Na+-pumps, generating a Na+ free energy gradient which serves as the energy source for several membrane anti- and symporter systems.
Highlights
Insulin and its plasma membrane receptor constitute an ancient response system critical to cell growth and differentiation
Insulin and insulin-like growth factors can act at the cell surface of the amphibian oocyte to initiate a cascade of events in preparation for cell division and differentiation, most studies use X. laevis ovarian follicles from females preinjected with progesterone
We have examined the cascade of insulin-induced plasma membrane events in order to characterize both the insulin receptor and the membrane enzyme systems modulated by insulin during the first meiotic division
Summary
Insulin and its plasma membrane receptor constitute an ancient response system critical to cell growth and differentiation. Studies using intact Rana pipiens oocytes have shown that insulin can act at receptors on the oocyte surface to initiate resumption of the first meiotic division. The structure of insulin, its receptor and the postreceptor signaling pathways have been highly conserved during evolution. As noted by Ebberink et al [1], the various phyla have had a polyphyletic origin: i.e., the four major groups - the chordates and vertebrates, the echinoderms and tentaculates, Insulin and insulin-like growth factors can act at the cell surface of the amphibian oocyte to initiate a cascade of events in preparation for cell division and differentiation (reviewed in [3,4]), most studies use X. laevis ovarian follicles from females preinjected with progesterone. Superfusion of isolated oocytes or follicles in an NMR tube maintains physiological oxygen levels and allows analysis of changes in bioenergetics, intracellular cation levels and in membrane conductance (e.g. [8])
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