scholarly journals Inhibitory Effect of Metformin on Oxidation of NADH-Dependent Substrates in Rat Liver Homogenate

2011 ◽  
pp. 835-839 ◽  
Author(s):  
E. PÁLENÍČKOVÁ ◽  
M. CAHOVÁ ◽  
Z. DRAHOTA ◽  
L. KAZDOVÁ ◽  
M. KALOUS

Metformin is widely used in the treatment of Type 2 diabetes, however, mechanisms of its antihyperglycemic effect were not yet fully elucidated. Complex I of mitochondrial respiration chain is considered as one of the possible targets of metformin action. In this paper, we present data indicating that the inhibitory effect of metformin can be tested also in liver homogenate. Contrary to previous findings on hepatocytes or mitochondria under our experimental conditions, lower metformin concentrations and shorter time of preincubation give significant inhibitory effects. These conditions enable to study the mechanism of the inhibitory effect of metformin in small samples of biological material (50-100 mg wet weight) and compare more experimental groups of animals because isolation of mitochonria is unnecessary.

2019 ◽  
Vol 14 (6) ◽  
pp. 1934578X1985912
Author(s):  
Phanindra Babu Kasi ◽  
Márta Kotormán

The formation of amyloid fibrils is associated with many human illnesses, such as Alzheimer’s, Huntington’s, and Parkinson’s diseases, amyotrophic lateral sclerosis, spongiform encephalitis, type 2 diabetes, and primary and secondary systemic amyloidosis. Nutrition contributes to the prevention of these diseases. The aim of our work was to look for commercially available fruit juices that can inhibit the formation of amyloid fibrils. Of the fruit juices that we examined, that of pomegranate was found to be the most effective inhibitory agent using turbidity measurements and Congo red binding assay. According to our experiments, pomegranate juice reduced the amount of PMS-trypsin amyloid-like fibrils to 3.7% at 5-fold dilution compared with the sample without pomegranate. The inhibitory effect of the pomegranate juice was concentration dependent.


Author(s):  
O. B. Furka

Introduction. Acetaminophen is an effective and safe drug for emergency usage, but there are contraindications for its usage. Diabetes mellitus is an endocrine disease, which caused by the absolute or relative deficiency of pancreas hormone (insulin).The aim of the study – to learn the change of energy supply oxidation indices in animals with type 2 diabetes mellitus and acetaminophen toxic lesions in time dynamics.Research Methods. We conducted two series of experiments. In the first series toxic lesion was caused by a single intragastric administration of acetaminophen suspension in 2 % starch solution to animals in a dose of 1250 mg/kg (1/2 LD50). In the second series the suspension of acetaminophen in 2 % starch solution in a dose of 55 mg/kg was given. Non-genetic form of experimental type 2 diabetes mellitus was modeled by a single intraperitoneal administration of streptozotocin solution in doses 65 mg/kg, which was diluted by citrate buffer (pH 4.5) with the previous intraperitoneal nicotinamide administration in doses of 230 mg/kg. Rats, which were given the same amount of solvent (citrate buffer pH 4.5), were used as the control group.Results and Discussion. Cytochrome oxidase and succinate dehydrogenase activity decreased in rat liver homogenate under the influence of acetaminophen with type 2 diabetes mellitus throughout the experiment.Conclusions. Acetaminophen administration to rats with type 2 diabetes mellitus causes significant violations of energy supply oxidation.


2017 ◽  
Vol 58 (10) ◽  
pp. 3826 ◽  
Author(s):  
Woo Hyun Han ◽  
Jonathan Gotzmann ◽  
Sharee Kuny ◽  
Hui Huang ◽  
Catherine B. Chan ◽  
...  

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1776 ◽  
Author(s):  
Zhihua Liu ◽  
Ying Yang ◽  
Wujun Dong ◽  
Quan Liu ◽  
Renyun Wang ◽  
...  

α-glucosidase inhibitors (AGIs) have been an important category of oral antidiabetic drugs being widely exploited for the effective management of type 2 diabetes mellitus. However, the marketed AGIs not only inhibited the disaccharidases, but also exhibited an excessive inhibitory effect on α-amylase, resulting in undesirable gastrointestinal side effects. Compared to these agents, Ramulus Mori alkaloids (SZ-A), was a group of effective alkaloids from natural Morus alba L., and showed excellent hypoglycemic effect and fewer side effects in the Phase II/III clinical trials. Thus, this paper aims to investigate the selective inhibitory effect and mechanism of SZ-A and its major active ingredients (1-DNJ, FA and DAB) on different α-glucosidases (α-amylase and disaccharidases) by using a combination of kinetic analysis and molecular docking approaches. From the results, SZ-A displayed a strong inhibitory effect on maltase and sucrase with an IC50 of 0.06 μg/mL and 0.03 μg/mL, respectively, which was similar to the positive control of acarbose with an IC50 of 0.07 μg/mL and 0.68 μg/mL. With regard to α-amylase, SZ-A exhibited no inhibitory activity at 100 μg/mL, while acarbose showed an obvious inhibitory effect with an IC50 of 1.74 μg/mL. The above analysis demonstrated that SZ-A could selectively inhibit disaccharidase to reduce hyperglycemia with a reversible competitive inhibition, which was primarily attributed to the three major active ingredients of SZ-A, especially 1-DNJ molecule. In the light of these findings, molecular docking study was utilized to analyze their inhibition mechanisms at molecular level. It pointed out that acarbose with a four-ring structure could perform desirable interactions with various α-glucosidases, while the three active ingredients of SZ-A, belonging to monocyclic compounds, had a high affinity to the active site of disaccharidases through forming a wide range of hydrogen bonds, whose affinity and consensus score with α-amylase was significantly lower than that of acarbose. Our study illustrates the selective inhibition mechanism of SZ-A on α-glucosidase for the first time, which is of great importance for the treatment of type 2 diabetes mellitus.


2009 ◽  
Vol 94 (4) ◽  
pp. 1372-1378 ◽  
Author(s):  
Rasmus Rabøl ◽  
Patricia M. V. Højberg ◽  
Thomas Almdal ◽  
Robert Boushel ◽  
Steen B. Haugaard ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ganiyu Oboh ◽  
Omodesola O. Ogunruku ◽  
Funke O. Ogidiolu ◽  
Adedayo O. Ademiluyi ◽  
Bukola C. Adedayo ◽  
...  

This study is aimed at assessing the inhibitory effect of teas on key enzymes (α-amylase andα-glucosidase) linked with type-2 diabetes and their antioxidant properties. Four samples of three brands were used; infusions of green tea (GT), 2 brands of black tea (BT), and a formulated herbal preparation for diabetes (ADT) (white tea,Radix Puerariae,Radix ophiopogonis, hawthorn berry, Chinese yam, and fragrant Solomon seal rhizome) were prepared and subsequently analyzed for their total phenol, ascorbic acid contents, antioxidant properties (2,2-Azizobis (3-Ethylbenzo-Thiazoline~6-sulfonate) “ABTS” scavenging ability and ferric reducing antioxidant property), and inhibition of pancreatic-α-amylase and intestinal-α-glucosidasein vitro. The study revealed that GT had the highest total phenol content, ascorbic acid content, ABTS* scavenging ability, and ferric reducing ability. Furthermore, all the teas inhibited Fe2+and sodium nitroprusside induced lipid peroxidation in pancreas, with GT having the highest inhibitory effect. Conversely, there was no significant difference (P>0.05) in the inhibitory effects of the teas onα-amylase andα-glucosidase. The antidiabetic property of the teas could be attributed to their inhibitory effect on carbohydrate hydrolyzing enzymes implicated in diabetes and their antioxidant activities.


2010 ◽  
Vol 12 (9) ◽  
pp. 806-814 ◽  
Author(s):  
R. Rabøl ◽  
R. Boushel ◽  
T. Almdal ◽  
C. N. Hansen ◽  
T. Ploug ◽  
...  

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