Effects of high glucose culture on EGF effects and EGF receptors in the LLC-PK1 cells.

We have shown that epidermal growth factor (EGF) may be important in diabetic renal hypertrophy. Since EGF is the most potent mitogen for the proximal tubule, it may be relevant to the cellular hyperplasia component in diabetic nephropathy. In order to further clarify the possible alterations of mitogenic effects of EGF on cultured renal cells in hyperglycemic states, the effects of high glucose culture on EGF-induced events and EGF receptors were studied in LLC-PK1 cells with equimolar mannitol being used as an osmotic control. The results showed that high glucose dose-dependently decreased mitogenesis while increasing cellular hypertrophy in LLC-PK1 cells. The dose-response curve of EGF-induced mitogenesis was similar in both normal (11 mM) and high (27.5 mM) glucose cultures. Meanwhile, EGF receptor number and affinity were not changed by high glucose in these cells. Furthermore, mannitol mimicked the growth-suppressive (but not hypertrophic) effects of high glucose cultures. Based upon these findings, we conclude that high glucose did not alter the mitogenic effects of EGF on the LLC-PK1 cells. This was associated with unchanged EGF receptor characteristics. Thus, concurrent with our previous studies, we speculate that it is the increased local EGF level, rather than an increased renal sensitivity to it, which is associated with hyperglycemic tubulopathy.