1.Regulation of leptin on insulin secretion and sulfonulurea receptor 1 transcription level in isolated rats pancreatic islets.
Li YUAN ; Hanxiang AN ; Xiuling DENG ; Zhuoya LI
Chinese Medical Journal 2003;116(6):868-872
OBJECTIVETo investigate the regulation of leptin on insulin secretion and expression of ATP-sensitive potassium channel subunit sulfonulurea receptor 1 (SUR1) mRNA, and to determine whether the effects of leptin are mediated through known intracellular signaling transduction.
METHODSPancreatic islets were isolated by the collagenase method from male SD rats. The purified islets were incubated with different concentrations of leptin for 2 h in the presence of different concentrations of glucose. Insulin release was measured using radioimmunoassay. Expression of SUR1 mRNA was detected by RT-PCR.
RESULTSIn the presence of leptin 2 nmol/L, insulin release was significantly inhibited at either 11.1 or 16.7 mmol/L glucose concentration (both P < 0.05), but insulin release was not altered at glucose of 5.6 mmol/L physiological concentration. The dose-response experiment showed that the maximal effect of leptin on insulin secretion achieved at 2 nmol/L. Exposure of islets to 2 nmol/L leptin induced a significant increase of SUR1 transcription levels by 71% (P < 0.01) at 11.1 mmol/L glucose and by 56% (P < 0.05) at 16.7 mmol/L glucose concentration. Selective phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin significantly prevented the leptin effect on insulin secretion and SUR1 mRNA expression.
CONCLUSIONSRegulatory effects of leptin on insulin secretion could be biphasic at different concentrations of glucose and leptin. The stimulatory regulation of SUR1 transcription levels may be mediated through activation of PI 3-kinase pathway, which may be a possible mechanism of leptin in regulating insulin secretion.
Animals ; Butadienes ; pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Insulin ; secretion ; Islets of Langerhans ; drug effects ; metabolism ; Leptin ; pharmacology ; Male ; Nitriles ; pharmacology ; Phosphatidylinositol 3-Kinases ; physiology ; Potassium Channels, Inwardly Rectifying ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley
2.Signaling pathways involved in the active components of Polygonum cuspidatum in treatment of nonalcoholic fatty liver disease and their interaction
Shudi LI ; Xinju CHEN ; Jiangkai LIU ; Zhen WANG ; Fei DUAN ; Zhuoya YUAN ; Lei LIANG ; Suling LI
Journal of Clinical Hepatology 2022;38(4):902-907
The pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear, and currently no effective drugs have been approved for the treatment of NAFLD. Polygonum cuspidatum is a natural traditional Chinese medicine with a long history of application, and studies have shown that it plays an important role in the treatment of NAFLD. This article summarizes related research findings in the active components of Polygonum cuspidatum applied in the treatment of NAFLD, and it is found that the active components of Polygonum cuspidatum can improve insulin resistance, exert an anti-oxidative stress effect, regulate lipid metabolism, improve endoplasmic reticulum stress, and alleviate inflammatory infiltration by regulating the signaling pathways including Nrf2, AMPK, NF-κB, SIRT1, and PPARα, thereby exerting a preventive and therapeutic effect on NAFLD, so as to provide a basis and ideas for developing drugs for NAFLD and exploring related mechanisms.
3.Mechanism of action of Polygonum multiflorum in inducing liver injury: A study based on signaling pathways
Zihan LIANG ; Jiahui LI ; Shuang CHENG ; Zhuoya YUAN ; Wenya RONG ; Yajie LIU ; Yujie HAO ; Ruilin WANG
Journal of Clinical Hepatology 2024;40(3):626-632
Polygonum multiflorum (PM), a commonly used Chinese herbal medicine in clinical practice, has been associated with frequent reports of liver injury in recent years, and the medication safety of PM has attracted more and more attention in China and globally. This article reviews the recent research advances in the signaling pathways and mechanisms of PM in causing drug-induced liver injury (DILI) and aims to provide new ideas for the proper and rational use of PM in clinical practice. The results show that PM is involved in the regulation of various signaling pathways, and it leads to the death of hepatocytes by destroying mitochondrial function, exacerbating bile acid accumulation, and inducing immune response, oxidative stress, and endoplasmic reticulum stress, thereby inducing the development and progression of DILI through multiple targets, pathways, and levels.