Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells. The tumor suppression effects of Ex-4 were associated with high expression of GLP-1R and activation of cyclic AMP (cAMP) and protein kinase A (PKA). Importantly, Ex-4 also downregulated epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3), which lie downstream of cAMP-PKA signaling, resulting in suppression of multiple STAT3-targeted genes including c-Myc, cyclin D1, survivin, Bcl-2 and Bcl-xl. The growth inhibitory effects of Ex-4 were consistent in GLP-1R-abundant hepatoma cell lines and xenograft mouse model, wherein both PKA and EGFR had obligatory roles in mediating Ex-4 functions. In addition, Ex-4 also effectively suppressed inflammatory and fibrotic phenotypes in mice fed with methionine-choline-deficient (MCD) diet and choline-deficient ethionine-supplemented (CDE) diet, respectively. In summary, Ex-4 elicits protective functions against NAFLD and obesity-associated HCC through cAMP-PKA-EGFR-STAT3 signaling, suggesting its administration as a novel approach to reduce HCC risk in diabetic patients.
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PMID:The anti-diabetic drug exenatide, a glucagon-like peptide-1 receptor agonist, counteracts hepatocarcinogenesis through cAMP-PKA-EGFR-STAT3 axis. 2831 60

We performed a network meta-analysis to compare the efficacy of 12 single-drug regimens (Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, Sitaglitin, Exenatide, Liraglutide, Acarbose, Benfluorex, and Glipizide) in the treatment of type 2 diabetes mellitus (T2DM). Fifteen relevant randomized controlled trials (RCTs) were included; direct and indirect evidence from these studies was combined, and weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRAs) were examined to evaluate the monotherapies. Liraglutide was more effective than Glimepiride, Pioglitazone, Sitaglitin, Exenatide, and Glipizide at reducing glycated hemoglobin (HbA1c) levels. In contrast, Acarbose was less effective than Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, and Liraglutide at decreasing HbA1c levels. Reductions in fasting plasma glucose (FPG) levels were similar after all treatments. Rosiglitazone was less effective than Glibenclamide and Repaglinide at reducing total cholesterol (TC) levels. High density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride levels did not differ after treatment with any of the monotherapies. HbA1c and FPG SUCRA values were highest for Liraglutide, while HbA1c and FPG values were lowest for Acarbose, and TC and LDL values were lowest for Rosiglitazone. These results suggest that Liraglutide may be most effective, and Acarbose least effective, at reducing blood glucose levels, while Glibenclamide, Repaglinide, and Metformin may be most effective, and Rosiglitazone least effective, at reducing lipoidemia, in T2DM patients.
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PMID:Comparison of twelve single-drug regimens for the treatment of type 2 diabetes mellitus. 2906 19