The use of gliclazide in the mirror of the individualized sulfonylurea therapy

2014 ◽  
Vol 155 (14) ◽  
pp. 541-548 ◽  
Author(s):  
Gábor Winkler

In addition to the common blood glucose lowering effect, sulfonylurea compounds are different in many aspects from each other. Based on earlier findings the second generation gliclazide has special advantages within this group. Although the number of experimental and clinical observations on gliclazide is continuously increasing, these novel findings are not in the focus anymore due to the appearance of new antidiabetics. The article overviews recent experimental (receptorial effect, the absence of Epac2 activation, antioxidant properties, possible incentive of factors participating in beta-cell differentiation) and pharmacogenomic data, and compares them with clinical observations obtained from gliclazide treatment (hypoglycaemias, parameters of cardiovascular outcome). The data underline the advantages of gliclazide, the highly pancreas-selective nature, preservation of the ischemic precondition, favourable hemodynamic properties and potential reduction of the beta-cell loss as compared to other compounds of the group. However, gliclazide is not free from disadvantages characteristic to sulfonylureas in general (blood glucose independent insulin stimulation, beta-cell depletion). Comparing gliclazide with other derivatives of the group, the above data indicate individual benefits for the application when sulfonylurea compound is the drug of choice. Orv. Hetil., 2014, 155(14), 541–548.

Proceedings ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 100
Author(s):  
Minerva C. García-Vargas ◽  
María del Mar Contreras ◽  
Irene Gómez-Cruz ◽  
Juan Miguel Romero-García ◽  
Eulogio Castro

Avocado has become fashionable due to its great organoleptic and nutritional properties. It is consumed as a fresh product and it is also processed to obtain salad oil and guacamole. In all cases, the only usable portion is the pulp. Therefore, to be a more sustainable and profitable agribusiness, it is important to recognize which compounds from the peel and the stone waste can be converted into valuable bio-products. Therefore, their chemical composition was determined according to the National Renewable Energy Laboratory, the total phenolic content by the Folin-Ciocalteu method and the antioxidant properties by the FRAP and TEAC assays. The main components of the peel and stone were acid-insoluble lignin (35.0% and 15.3%, respectively), polymeric sugars (23.6% and 43.9%, respectively), and the aqueous extractives (15.5% and 16.9%, respectively). Both biomasses contain lipids and protein, but a minor proportion (<6%). The valorization of lignin and sugars is of interest given the high content; stones are a rich source of glucose (93.2% of the polymeric fraction), which could be used to obtain biofuels or derivatives of interest. The extractive fraction of the peel contained the highest number of phenolic compounds (4.7 g/100 g biomass), mainly concentrated in the aqueous fraction (i.e., 87%) compared to the ethanol one, which was subsequently extracted. It correlated with major antioxidant activity and, therefore, the peel can be applied to obtain antioxidants and water can be used as an environmentally friendly extraction solvent.


2020 ◽  
Vol 64 (4) ◽  
pp. 235-248 ◽  
Author(s):  
Karin J Bosma ◽  
Mohsin Rahim ◽  
Kritika Singh ◽  
Slavina B Goleva ◽  
Martha L Wall ◽  
...  

The G6PC1, G6PC2 and G6PC3 genes encode distinct glucose-6-phosphatase catalytic subunit (G6PC) isoforms. In mice, germline deletion of G6pc2 lowers fasting blood glucose (FBG) without affecting fasting plasma insulin (FPI) while, in isolated islets, glucose-6-phosphatase activity and glucose cycling are abolished and glucose-stimulated insulin secretion (GSIS) is enhanced at submaximal but not high glucose. These observations are all consistent with a model in which G6PC2 regulates the sensitivity of GSIS to glucose by opposing the action of glucokinase. G6PC2 is highly expressed in human and mouse islet beta cells however, various studies have shown trace G6PC2 expression in multiple tissues raising the possibility that G6PC2 also affects FBG through non-islet cell actions. Using real-time PCR we show here that expression of G6pc1 and/or G6pc3 are much greater than G6pc2 in peripheral tissues, whereas G6pc2 expression is much higher than G6pc3 in both pancreas and islets with G6pc1 expression not detected. In adult mice, beta cell-specific deletion of G6pc2 was sufficient to reduce FBG without changing FPI. In addition, electronic health record-derived phenotype analyses showed no association between G6PC2 expression and phenotypes clearly unrelated to islet function in humans. Finally, we show that germline G6pc2 deletion enhances glycolysis in mouse islets and that glucose cycling can also be detected in human islets. These observations are all consistent with a mechanism by which G6PC2 action in islets is sufficient to regulate the sensitivity of GSIS to glucose and hence influence FBG without affecting FPI.


Author(s):  
Anand Tekriwal ◽  
Mario J. Lintz ◽  
John A Thompson ◽  
Gidon Felsen

Parkinsonian motor deficits are associated with elevated inhibitory output from the basal ganglia (BG). However, several features of Parkinson's disease (PD) have not been accounted for by this simple "classical rate model" framework, including the observation in PD patients that movements guided by external stimuli are less impaired than otherwise-identical movements generated based on internal goals. Is this difference due to divergent processing within the BG itself, or to the recruitment of extra-BG pathways by sensory processing? In addition, surprisingly little is known about precisely when, in the sequence from selecting to executing movements, BG output is altered by PD. Here, we address these questions by recording activity in the SNr, a key BG output nucleus, in hemiparkinsonian mice performing a well-controlled behavioral task requiring stimulus-guided and internally-specified directional movements. We found that hemiparkinsonian mice exhibited a bias ipsilateral to the side of dopaminergic cell loss that was stronger when movements were internally specified rather than stimulus guided, consistent with clinical observations in parkinsonian patients. We further found that changes in parkinsonian SNr activity during movement preparation were consistent with the ipsilateral behavioral bias, as well as its greater magnitude for internally-specified movements. While these findings are inconsistent with some aspects of the classical rate model, they are accounted for by a related "directional rate model" positing that SNr output phasically over-inhibits motor output in a direction-specific manner. These results suggest that parkinsonian changes in BG output underlying movement preparation contribute to the greater deficit in internally-specified than stimulus-guided movements.


Author(s):  
Kamadyaapa Davie Rexon ◽  
Gondwe Mavuto Masopera ◽  
Shauli Mathulo ◽  
Sewani Rusike Constance ◽  
Nkeh Chungag Benedicta

  Objective: This study was conducted to scientifically evaluate the antidiabetic and antioxidant effects of ethanolic leaf extract of Erythrina abbysinica (EEA).Methods: Acute and sub-chronic effects of EEA at 100, 200, and 400 mg/kg/bwt and glibenclamide (GL) at 5 mg/kg/bwt. were evaluated in both normal and streptozotocin (STZ)-induced diabetic male Wistar rats (250–300 g). The acute studies were performed using oral glucose tolerance test (OGTT). In sub-chronic studies, animals were orally administered with EEA and GL daily for 6 w. Brine shrimp assay was used to determine the toxicity of EEA. 1, 1-diphenyl-2-picrylhydrazyl, ferric reducing capacity of plasma, and thiobarbituric acid reactive substances assays were used to determine antioxidant properties of EEA.Results: Following OGTT, EEA significantly (p<0.05) and dose-dependently (100, 200, and 400 mg/kg/bwt) decreased blood glucose levels in both normal and STZ-induced diabetic rats when compared with positive and negative control counterparts at all-time points, whereas GL significantly (p<0.05) decreased blood glucose only in normal rats but not in diabetic rats. Daily, oral administration of EEA for 6 w significantly (p<0.05) and dose-dependently (100, 200, and 400 mg/kg/bwt) decreased blood glucose levels in STZ-induced diabetic rats when compared with the diabetic control group. EEA revealed weak toxicity with a lethal concentration50 value of 997 μg/ml). Furthermore, EEA showed significant free radical scavenging, total antioxidant, and anti-lipid peroxidative capacities.Conclusion: The study has shed more light on the scientific basis for the use of E. abbysinica in management of diabetes in some communities of Eastern Cape of South Africa.


Diabetologia ◽  
2011 ◽  
Vol 55 (2) ◽  
pp. 382-391 ◽  
Author(s):  
S. Kautz ◽  
L. van Bürck ◽  
M. Schuster ◽  
E. Wolf ◽  
R. Wanke ◽  
...  

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