Cultured retinal pigment epithelium cells from donors with type I diabetes show an altered insulin response.
Retinal pigment epithelium (RPE) isolated from 13 of 49 eyes of donors with insulin-dependent diabetes produced viable, proliferating cultures. No difference was found in baseline glucose uptake and lactate production, as measured by 13C and 1H nuclear magnetic resonance, between the RPE cells from diabetic donors and those cultured from normal donors. Insulin-mediated stimulation of glucose uptake and lactate production was decreased significantly in the RPE cells from diabetic donors compared with those from normal controls. Oxygen consumption and the percentage of endogenous oxygen consumption from fatty-acid oxidation, determined by using a specific inhibitor, were similar in both groups. Cellular proliferation and endocytosis, measured by liposome uptake, also were stimulated by insulin similarly in both types of cells. These results show that at least one or more mechanisms of insulin action in the RPE, thought to be a noninsulin-dependent tissue, may be altered permanently by chronic insulin-dependent diabetes. This finding may have implications for the pathogenesis of disease in noninsulin-dependent tissues even in patients with tight glycemic control.
LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans.
M V
MV
Miceli
D A
DA
Newsome
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000473:pathology
D007328:Insulin; D007773:Lactates; D008081:Liposomes; D019344:Lactic Acid; D005947:Glucose