详细记录  
题名:Effects of chronic exposure of clonal beta-cells to elevated glucose and free fatty acids on incretin receptor gene expression and secretory responses to GIP and GLP-1.
作者:PATHAK V; VASU S; FLATT PR; IRWIN N;
来源:Diabetes Obes Metab. 2013 Oct 26. doi: 10.1111/dom.12227. [ IF= 0.00 ] ]
URL :10.1111/dom.12227
日期:20131104
摘要:AIM: The incretin effect, mediated by glucose-dependent insulinotropic
polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), is impaired in type 2
diabetes. MATERIALS AND METHODS: The present study examines the effects of
prolonged exposure to elevated glucose and free fatty acids in clonal BRIN BD11
cells on GIP and GLP-1 action. RESULTS: Glucotoxic conditions (18 h) had no
effect on GIP- or GLP-1-mediated insulinotropic responses. In contrast, 48 h
glucotoxic culture impaired (p < 0.05 to p < 0.001) insulin release in response
to GLP-1, and particularly GIP. Culture under lipotoxic conditions (18 h)
impaired (p < 0.05 to p < 0.001) the insulin-releasing effect of GIP, but was
without effect on GLP-1. However, 48 h lipotoxic culture compromised both GIP (p
< 0.05 to p < 0.001) and GLP-1 (p < 0.05 to p < 0.01) insulin-releasing actions.
Glucolipotoxic culture (18 h) completely annulled the insulinotropic action of
GIP, whereas GLP-1 effects were similar to control. However, when glucolipotoxic
culture was extended to 48 h, both GIP- and GLP-1-mediated effects were (p < 0.05
to p < 0.001) impaired. Assessment of cell viability, number and insulin content
revealed detrimental (p < 0.05 to p < 0.001) effects under all culture
conditions, barring 18 h glucotoxic and lipotoxic culture. Finally, GIP-R gene
and protein expression was increased (p < 0.05 to p < 0.01) under glucotoxic
culture, with decreased (p < 0.05 to p < 0.001) expression following
glucolipotoxic culture. GLP-1-R gene expression followed a similar trend, but
protein levels were generally reduced under all culture conditions. CONCLUSION:
The results indicate that impaired insulinotropic response to GIP and GLP-1 under
diabetic milieu involves mechanisms beyond simple expression of respective
receptors.

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