Session: OR13-Systemic Regulation of Islet Development & Function
Room 304 (Moscone Center)
PRL treatment results in a 5.5±0.5-fold increase in BrdU labeling, oleate a 3.5±0.5-fold increase and synergizes with PRL to a 14.2±1.5-fold increase (n=16, p<0.01). Similar results were obtained when using Ki-67 or PCNA to determine cell proliferation and further confirmed with Western analysis of PCNA. Synergy between PRL and oleate was seen with both neonatal and adult islets. Unsaturated fatty acids (FA) palmitoleate (18-fold) and linoleate (13-fold) also induce synergy, but not the saturated FA palmitate. While synergy was seen with oleate and PRL, it was not observed with oleate and GH, GLP-I, EGF or EGF+IGF.
To examine the effects of PRL and oleate on islet mass, islets were cultured for 14 days and each islet photographed on alternate days. The volume was determined to estimate the growth rate. Neonatal islet growth was -0.4±.5%/day for control, 3.7±0.8%/day for PRL, 0.4±0.8%/day for oleate and 7.2±1.3%/day for PRL+oleate (n=8, p<0.01). This represents a 16 day doubling time for the PRL/oleate treated islets. Adult islet growth was -0.5±0.3%/day for control, 1.4±0.3%/day for PRL, 0.1±0.2%/day for oleate and 3.2±0.5%/day for PRL+oleate (n=7, p<0,05). This represents a 32 day doubling time for the PRL/oleate treated adult islets. Approximately two thirds of the islet growth is from an increase in cell volume and one third from cell number.
Inhibition of FA oxidation (etomoxir) had no effect on cell division or synergy between PRL and oleate. In contrast, inhibition of fatty acylCoA synthetase (Triacin C) reduced cell division by approximately 50% in all groups (control, PRL, oleate and oleate/PRL) without affecting the synergy seen between PRL and oleate. Similarly, PKCζ inhibition and MEK inhibition (U0126) reduced cell division in all groups without affecting synergy (n=5, p<0.05).
The results suggest that the increase in β cell growth during pregnancy represents the combined effects of PRL/PL and FAs however, the mechanisms for synergy between prolactin and oleate remain unclear.
Nothing to Disclose: RLS, NB, LS, TCB
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