Search Results
You are looking at 1 - 5 of 5 items for
- Author: Jinning Lou x
- Refine by access: All content x
Search for other papers by Jian-Ting Ke in
Google Scholar
PubMed
Search for other papers by Mi Li in
Google Scholar
PubMed
Search for other papers by Shi-Qing Xu in
Google Scholar
PubMed
Search for other papers by Wen-Jian Zhang in
Google Scholar
PubMed
Search for other papers by Yong-Wei Jiang in
Google Scholar
PubMed
Search for other papers by Lan-yun Cheng in
Google Scholar
PubMed
Search for other papers by Li Chen in
Google Scholar
PubMed
Search for other papers by Jin-Ning Lou in
Google Scholar
PubMed
Search for other papers by Wei Wu in
Google Scholar
PubMed
The efficacy of gliquidone for the treatment of diabetic nephropathy was investigated by implanting micro-osmotic pumps containing gliquidone into the abdominal cavities of Goto-Kakizaki (GK) rats with diabetic nephropathy. Blood glucose, 24 h urinary protein, and 24 h urinary albumin levels were measured weekly. After 4 weeks of gliquidone therapy, pathological changes in the glomerular basement membrane (GBM) were examined using an electron microscope. Real-time PCR, western blotting, and immunohistochemistry were employed to detect glomerular expression of receptors for advanced glycation end products (RAGE) (AGER), protein kinase C β (PKCβ), and protein kinase A (PKA) as well as tubular expression of the albumin reabsorption-associated proteins: megalin and cubilin. Human proximal tubular epithelial cells (HK-2 cells) were used to analyze the effects of gliquidone and advanced glycation end products (AGEs) on the expression of megalin and cubilin and on the absorption of albumin. Gliquidone lowered blood glucose, 24 h urinary protein, and 24 h urinary albumin levels in GK rats with diabetic nephropathy. The level of plasma C-peptide increased markedly and GBM and podocyte lesions improved dramatically after gliquidone treatment. Glomerular expression of RAGE and PKCβ decreased after gliquidone treatment, while PKA expression increased. AGEs markedly suppressed the expression of megalin and cubulin and the absorption of albumin in HK-2 cells in vitro, whereas the expression of megalin and cubilin and the absorption of albumin were all increased in these cells after gliquidone treatment. In conclusion, gliquidone treatment effectively reduced urinary protein in GK rats with diabetic nephropathy by improving glomerular lesions and promoting tubular reabsorption.
Search for other papers by Xiuli Men in
Google Scholar
PubMed
Search for other papers by Liang Peng in
Google Scholar
PubMed
Search for other papers by Haiyan Wang in
Google Scholar
PubMed
Search for other papers by Wenjian Zhang in
Google Scholar
PubMed
Search for other papers by Shiqing Xu in
Google Scholar
PubMed
Search for other papers by Qing Fang in
Google Scholar
PubMed
Search for other papers by Honglin Liu in
Google Scholar
PubMed
Search for other papers by Wenying Yang in
Google Scholar
PubMed
Search for other papers by Jinning Lou in
Google Scholar
PubMed
The calcium-regulated transcription coactivator, Ca2 +-responsive transactivator (CREST) was expressed in pancreatic β-cells. Moreover, CREST expression became significantly increased in pancreatic islets isolated from hyperglycemic Goto–Kakizaki rats compared with normoglycemic Wistar controls. In addition, culture of β-cells in the presence of high glucose concentrations also increased CREST expression in vitro. To further investigate the role of this transactivator in the regulation of β-cell function, we established a stable β-cell line with inducible CREST expression. Hence, CREST overexpression mimicked the glucotoxic effects on insulin secretion and cell growth in β-cells. Moreover, high glucose-induced apoptosis was aggravated by upregulation of the transactivator but inhibited when CREST expression was partially silenced by siRNA technology. Further investigation found that upregulation of Bax and downregulation of Bcl2 was indeed induced by its expression, especially under high glucose conditions. In addition, as two causing factors leading to β-cell apoptosis under diabetic conditions, endoplasmic reticulum stress and high free fatty acid, mimicked the high glucose effects on CREST upregulation and generation of apoptosis in β-cells, and these effects were specifically offset by the siRNA knockdown of CREST. These results indicated that CREST is implicated in β-cell apoptosis induced by culture in high glucose and hence that CREST may become a potential pharmacological target for the prevention and treatment of type 2 diabetes mellitus.
Graduate School of Peking Union Medical College, Institute of Clinical Medical Sciences, Department of Cell Physiology and Metabolism, Beijing 100730, People's Republic of China
Search for other papers by Bo Qian in
Google Scholar
PubMed
Search for other papers by Haiyan Wang in
Google Scholar
PubMed
Search for other papers by Xiuli Men in
Google Scholar
PubMed
Search for other papers by Wenjian Zhang in
Google Scholar
PubMed
Search for other papers by Hanqing Cai in
Google Scholar
PubMed
Search for other papers by Shiqing Xu in
Google Scholar
PubMed
Search for other papers by Yaping Xu in
Google Scholar
PubMed
Search for other papers by Liya Ye in
Google Scholar
PubMed
Search for other papers by Claes B Wollheim in
Google Scholar
PubMed
Search for other papers by Jinning Lou in
Google Scholar
PubMed
We found that TRIB3, an endogenous inhibitor of Akt (PKB), is expressed in pancreatic β-cells. The TRIB3 expression is significantly increased in islets isolated from hyperglycemic Goto–Kakizaki rats compared with normal glycemic controls. In vitro high glucose treatment also resulted in increased TRIB3 expression in rat INS1 cells. To investigate the role of TRIB3 in the regulation of β-cell function, we established an INS1 stable cell line allowing inducible expression of TRIB3. We demonstrated that overexpression of TRIB3 mimicked the glucotoxic effects on insulin secretion and cell growth in INS1 cells. Moreover, induction of TRIB3 also synergistically enhanced high-glucose-elicited apoptosis in INS1 cells, whereas siRNA knock-down of TRIB3 showed the opposite effects. We also confirmed that the ΔΨm of mitochondria was decreased, caspase-3 activity was up-regulated and reactive oxygen species content was increased in TRIB3 overexpressing β cells in high glucose condition. Most interestingly, the oestrogen receptor (ER) stress inducer, thapsigargin, mimicked the high glucose effects on up-regulation of TRIB3 and generation of apoptosis in cultured INS1 cells. These effects were specifically prevented by siRNA knock down of TRIB3. We therefore conclude that TRIB3 is implicated in glucotoxicity- and ER stress-induced β-cell failure. TRIB3 could be a potential pharmacological target for prevention and treatment of type 2 diabetes.
Search for other papers by Bo Qian in
Google Scholar
PubMed
Search for other papers by Haiyan Wang in
Google Scholar
PubMed
Search for other papers by Xiuli Men in
Google Scholar
PubMed
Search for other papers by Wenjian Zhang in
Google Scholar
PubMed
Search for other papers by Hanqing Cai in
Google Scholar
PubMed
Search for other papers by Shiqing Xu in
Google Scholar
PubMed
Search for other papers by Yaping Xu in
Google Scholar
PubMed
Search for other papers by Liya Ye in
Google Scholar
PubMed
Search for other papers by Claes B Wollheim in
Google Scholar
PubMed
Search for other papers by Jinning Lou in
Google Scholar
PubMed
Search for other papers by Bo Qian in
Google Scholar
PubMed
Search for other papers by Haiyan Wang in
Google Scholar
PubMed
Search for other papers by Xiuli Men in
Google Scholar
PubMed
Search for other papers by Wenjian Zhang in
Google Scholar
PubMed
Search for other papers by Hanqing Cai in
Google Scholar
PubMed
Search for other papers by Shiqing Xu in
Google Scholar
PubMed
Search for other papers by Yaping Xu in
Google Scholar
PubMed
Search for other papers by Liya Ye in
Google Scholar
PubMed
Search for other papers by Claes B Wollheim in
Google Scholar
PubMed
Search for other papers by Jinning Lou in
Google Scholar
PubMed
