Kirti V. Patel

Combination of omeprazole with GLP-1 agonist therapy improves insulin sensitivity and antioxidant activity in liver in type 1 diabetic mice

BACKGROUND Combination with suitable pharmacological agents can improve the antiobesity and antidiabetic actions of glucagon like peptide-1 (GLP-1) based therapies. GLP-1 agonist exendin-4 may have insulin-independent effects on amelioration of insulin resistance and hepatic steatosis by virtue of its action on hepatic GLP-1 receptors, and these effects can be improved by combination with proton pump inhibitors. However, it was not assessed whether omeprazole can improve the peripheral actions of exendin-4 in the state of insulin deficiency. METHODS We investigated the effects of combination of omeprazole with GLP-1 agonist exendin-4 in multiple low-dose streptozotocin (STZ)-induced diabetes in C57BL/KsJ mice, a model of type 1 diabetes. Male diabetic mice were treated with exendin-4 and/or omeprazole for a period of 4 weeks. RESULTS Omeprazole treatment had no significant effect on lowering the blood glucose levels of diabetic mice, when compared to control, although it improved the antihyperglycemic actions of exendin-4. Similarly, serum triglycerides and total cholesterols levels were significantly lower in the combination treated mice compared to either exendin-4 and omeprazole alone. In addition, the combination treatment significantly ameliorated lipid peroxidation and hepatic triglycerides in diabetic mice compared to either exendin-4 and omeprazole alone. The improvement in hepatic insulin sensitivity, as indicated by insulin tolerance test (ITT) and pyruvate tolerance test (IPPTT), was correlated with the expression of nuclear factor erythroid-related factor 2 (Nrf2) and insulin receptor substrate-1 (IRS-1) and the combination treatment significantly improved the insulin sensitivity in comparison to vehicle control. CONCLUSION We conclude that combination with omeprazole improves the insulin sensitizing actions of GLP-1 therapy and these effects are partially mediated through the decrease in hepatic steatosis and improvement in antioxidant status in the liver.

Omeprazole improves the anti-obesity and antidiabetic effects of exendin-4 in db/db mice (奥美拉唑改善唾液素-4 对db/db小鼠的减肥与降糖作用)*

Background:  In addition to its glucoregulatory actions, exendin‐4, a stable glucagon‐like peptide‐1 receptor agonist, exhibits protective effects in the pancreas and anti‐obesity effects. Suitable combination treatment with other anti‐obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin‐4 in db/db mice, an experimental model of obesity and type 2 diabetes.

Validated HPTLC method for quantification of myricetin in the stem bark of Myrica esculenta Buch. Ham. Ex D. Don, myricaceae

A simple, rapid, and precise high-performance thin-layer chromatographic method has been established for quantitative analysis of myricetin in the stem bark of Myrica esculenta, family Myricaceae. The marker myricetin was separated from other components of stem bark extract on silica gel 60 F254 HPTLC plates with toluene-ethyl acetate-formic acid-methanol 3:3:0.6:0.4 (v/v) as mobile phase. Densitometry in absorbance-reflection mode at 268 nm was used for quantitative analysis of myricetin. The stem bark of M. esculenta was found to contain 0.225% (w/w) myricetin. The method was validated for linearity, accuracy, precision, and specificity in accordance with ICH guidelines. The calibration plot was linear between 0.4 and 2.0 µg per band for myricetin. The limits of detection and quantitation were 0.0939 and 0.2845 µg per band, respectively. The method can be used as a quality control-method for fingerprint profiling and quantitative analysis of the stem bark of Myrica esculenta.

Is cytochrome modulation the new frontier for decreasing the risk of cataract

Aim: The present study was designed to study the effect of cytochrome P450 (CYP) modulators on the occurrence of cataract using male Sprague-Dawley rats weighing 40:50 gm. Materials and Methods: Macroscopical examination of the lens isolated from rats pretreated with diltiazem (30 mg/kg; once daily; PO) showed delayed occurrence of cataract while pioglitazone (3.8 mg/kg; once daily; PO) pretreatment demonstrated an early cataract. Results and Conclusion: A delayed occurrence of cataract with diltiazem (CYP inhibitor) and an early onset of cataract with pioglitazone (CYP inducer) indicate that a cytochrome P450 mediated pathway may affect the initiation of cataract but not the maturation pattern.

Validated HPTLC Method for Quantification of Luteolin and Apigenin in Premna mucronata Roxb., Verbenaceae.

A simple, rapid, and precise high-performance thin-layer chromatographic method was developed for quantitative estimation of luteolin and apigenin in Premna mucronata Roxb., family Verbenaceae. Separation was performed on silica gel 60 F254 HPTLC plates using toluene : ethyl acetate : formic acid (6 : 4 : 0.3) as mobile phase for elution of markers from extract. The determination was carried out in fluorescence mode using densitometric absorbance-reflection mode at 366 nm for both luteolin and apigenin. The methanolic extract of Premna mucronata was found to contain 10.2 mg/g % luteolin and 0.165 mg/g % of apigenin. The method was validated in terms of linearity, LOD and LOQ, accuracy, precision, and specificity. The calibration curve was found to be linear between 200 and 1000 ng/band for luteolin and 50 and 250 ng/band for apigenin. For luteolin and apigenin, the limit of detection was found to be 42.6 ng/band and 7.97 ng/band while the limit of quantitation was found to be 129.08 ng/band and 24.155 ng/band, respectively. This developed validated method is capable of quantifying and resolving luteolin and apigenin and can be applicable for routine analysis of extract and plant as a whole.

Omeprazole improves the anti-obesity and antidiabetic effects of exendin-4 indb/dbmice (奥美拉唑改善唾液素-4 对db/db小鼠的减肥与降糖作用)*: Omeprazole improves exendin-4 activity

Background:  In addition to its glucoregulatory actions, exendin‐4, a stable glucagon‐like peptide‐1 receptor agonist, exhibits protective effects in the pancreas and anti‐obesity effects. Suitable combination treatment with other anti‐obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin‐4 in db/db mice, an experimental model of obesity and type 2 diabetes.