Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesangial cells are thought to play a central role in the renal complications of diabetes mellitus. Insulin-like growth factor I (IGF-I) has been found to promote mesangial cell proliferation and regulate normal mesangial cell function in an autocrine and/or paracrine fashion. To gain further insight into the potential regulatory role IGF-I may play in mesangial cell function in diabetes, IGF-I receptors were analyzed in mesangial cells isolated from diabetic mice (db/db) and their control littermates (db/m). Mesangial cells isolated from db/db mice exhibited higher levels of IGF-I receptors compared to cells from db/m mice. Insulin receptors were not detectable in either cell type by binding analyses; however, immunoblot analysis revealed insulin receptor alpha-subunits in wheat germ agglutinin-Sepharose-purified membranes from db/db cells. Northern blot analysis further indicated a lack of detectable insulin receptor mRNA in db/m cells, whereas db/db cells expressed multiple insulin receptor mRNA transcripts. Both IGF-I and insulin receptor mRNA levels were increased in db/db cells grown in the presence of high glucose (28 mM), whereas the receptor protein levels remained relatively constant or increased, respectively. This increased expression of IGF-I and insulin receptors in diabetic mesangial cells may have an important role in the development of diabetic nephropathy.
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PMID:Regulation of insulin-like growth factor I receptors in diabetic mesangial cells. 184 26

The complications of diabetes arise in part from abnormally high cellular glucose uptake and metabolism. To determine whether altered glucose transporter expression may be involved in the pathogenesis of diabetic nephropathy, we investigated the effects of elevated extracellular glucose concentrations on facilitative glucose transporter (GLUT) expression in rat mesangial cells. GLUT1 was the only transporter isoform detected. Cells exposed to 20 mmol/l glucose medium for 3 days demonstrated increases in GLUT1 mRNA (134%, P < 0.002), GLUT1 protein (68%, P < 0.02), and V(max) (50%, P < 0.05) for uptake of the glucose analog [3H]2-deoxyglucose (3H2-DOG), when compared to cells chronically adapted to physiologic glucose concentrations (8 mmol/l). The increase in GLUT1 protein was sustained at 3 months, the latest time point tested (77% above control, P < 0.01). In contrast, hypertonic mannitol had no effect on GLUT1 protein levels. Insulin-like growth factor I (IGF-I; 30 ng/ml) increased the uptake of 3H2-DOG by 28% in 8 mmol/l glucose-treated cells (P < 0.05) and by 75% in cells switched to 20 mmol/l glucose for 3 days (P < 0.005). These increases in 3H2-DOG uptake occurred despite a lack of effect of IGF-I on GLUT1 protein levels (P > 0.5 vs. control). Therefore, hyperglycemia and IGF-I treatment both lead to increases in mesangial cell glucose uptake, and hyperglycemia induces increased GLUT1 expression, which can directly lead to the pathological changes of diabetic nephropathy. The effects of high glucose and of IGF-I to stimulate 3H2-DOG uptake also appear to be additive.
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PMID:D-glucose stimulates mesangial cell GLUT1 expression and basal and IGF-I-sensitive glucose uptake in rat mesangial cells: implications for diabetic nephropathy. 916 76