Oxamate Enhances the Anti-Inflammatory and Insulin-Sensitizing Effects of Metformin in Diabetic Mice

Pharmacology ◽  
2017 ◽  
Vol 100 (5-6) ◽  
pp. 218-228 ◽  
Author(s):  
Mu-chao Wu ◽  
Wei-ran Ye ◽  
Yi-jia Zheng ◽  
Shan-shan Zhang

Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice. These results show that OXA enhances the anti-inflammatory and insulin-sensitizing effects of MET through the inhibition of tissue lactate production in db/db mice.

2011 ◽  
Vol 26 (6) ◽  
pp. 535-540 ◽  
Author(s):  
Anibal Basile-Filho ◽  
Edson Antonio Nicolini ◽  
Maria Auxiliadora-Martins ◽  
Orlando de Castro e Silva Jr

PURPOSE: To evaluate the accuracy of different parameters in predicting early (one-month) mortality of patients submitted to orthotopic liver transplantation (OLT). METHODS: This is a retrospective study of forty-four patients (38 males and 10 females, mean age of 52.2 ± 8.9 years) admitted to the Intensive Care Unit of a tertiary hospital. Serial lactate blood levels, APACHE II, MELD post-OLT, creatinine, bilirubin and INR parameters were analyzed by receiver-operator characteristic (ROC) curves as evidenced by the area under the curve (AUC). The level of significance was set at 0.05. RESULTS: The mortality of OLT patients within one month was 17.3%. Differences in blood lactate levels became statistically significant between survivors and nonsurvivors at the end of the surgery (p<0.05). The AUC was 0.726 (95%CI = 0.593-0.835) for APACHE II (p = 0.02); 0.770 (95%CI = 0.596-0.849) for blood lactate levels (L7-L8) (p = 0.03); 0.814 (95%CI = 0.690-0.904) for MELD post-OLT (p < 0.01); 0.550 (95%CI = 0.414-0.651) for creatinine (p = 0.64); 0.705 (95%CI = 0.571-0.818) for bilirubin (p = 0.05) and 0.774 (95%CI = 0.654-0.873) for INR (p = 0.02). CONCLUSION: Among the studied parameters, MELD post-OLT was more effective in predicting early mortality after OLT.


2019 ◽  
Vol 25 (1) ◽  
pp. 30-34 ◽  
Author(s):  
Francisco Sérgio Lopes Vasconcelos Filho ◽  
Mateus Bastos de Souza ◽  
Jefferson Pacheco Amaral Fortes ◽  
Karla Camila Lima de Souza ◽  
Mayara Rangel Araújo Carneiro ◽  
...  

ABSTRACT Objective: To propose a duathlon model adapted for rats (associated swimming and running training) and compare it with the individual activities carried out separately, considering the glucose uptake and serum lactate production mechanism. Methods: Twenty-eight 90-day-old Wistar rats with a mean weight of 150-200 g were used. The animals were divided into four groups: control group, swimming group, running group, and swimming/running group. These animals were adapted to their respective training programs for three days and underwent the 4-week training protocol soon afterwards. Pre- and post-training blood lactate and blood glucose analyses were performed at the end of each week. Statistical difference was considered when the p value was less than 0.01 (p <0.01). Results: There was a decrease in glycemic levels and an increase in lactate levels in the swimming and swimming/running groups throughout the training period, which did not occur in the running group. Conclusion: The duathlon model adapted for rats proved satisfactory in terms of the production and stabilization of blood lactate levels. Level of evidence II; Therapeutic Studies - Investigating the Results of Treatment.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jovanovic Aleksandar ◽  
Peric Vladan ◽  
Snezana Markovic-Jovanovic ◽  
Radojica Stolic ◽  
Jadranka Mitic ◽  
...  

Background.Increased lactate production is frequent in unregulated/complicated diabetes mellitus.Methods.Three groups, each consisting of 40 patients (type 2 diabetics with myocardial infarction, DM+AMI, nondiabetics suffering myocardial infarction, MI, and diabetics with no apparent cardiovascular pathology, DM group), were tested for pH, serum bicarbonate and electrolytes, blood lactate, and CK-MB.Results. Blood lactate levels were markedly higher in AMI+DM compared to MI group (4.54±1.44versus3.19±1.005 mmol/L,p<0.05); they correlated with the incidence of heart failure(ρ=0.66), cardiac rhythm disorders(ρ=0.54), oxygen saturation(ρ=0.72), CK-MB levels(ρ=0.62), and poor short-term outcome. Lactic acidosis in DM+AMI group was not always related to lethal outcome.Discussion. The lactate cutoff value associated with grave prognosis depends on the specific disease. While some authors proposed cutoff values ranging from 0.76 to 4 mmol/L, others argued that only occurrence of lactic acidosis may be truly predictive of lethal outcome.Conclusion. Both defective glucose metabolism and low tissue oxygenation may contribute to the lactate production in diabetic patients with acute myocardial infarction; high lactate levels indicate increased risk for poor outcome in this population comparing to nondiabetic patients. The rise in blood lactate concentration in diabetics with AMI was associated with increased incidence of heart failure, severe arrhythmias, cardiogenic shock, and high mortality rate.


Author(s):  
Suman Shivanagouda Patil ◽  
Sukanya . ◽  
Suman Rath ◽  
Carolin Elizabeth George

Background: Perinatal asphyxia is a major cause of neonatal and childhood morbidity and mortality. Electronic foetal monitoring is used routinely to know the condition of the baby during Intrapartum period. Normal trace correlates highly with absence of acidemia at birth. Abnormal trace needs further evaluation. In order to better define the metabolic status of the new born, umbilical lactate levels have been measured. Objectives of this study were to determine the validity of umbilical cord blood lactate levels in predicting the adverse early neonatal outcome in babies with intrapartum foetal distress and to compare the validity of umbilical cord blood lactate and umbilical artery pH in predicting adverse neonatal outcome in babies with intrapartum foetal distress.Methods: 295 pregnant women with abnormal CTG in active labour were subjected for estimation of cord blood lactate and umbilical artery pH immediately after delivery and were compared in predicting adverse neonatal outcome.Results: In the present study specificity of serum lactate (97.7%) and umbilical artery pH (95.97%) was almost similar in babies with Apgar <7 at 1 minute and 5 minutes, but sensitivity of serum lactate (23.14%) and cord ph (31.4%) was less in babies with Apgar score ≤7 at 1 minute. Area under ROC showed serum lactate is more accurate in predicting adverse neonatal outcome compared to umbilical artery pH.Conclusions: Umbilical cord blood lactate is more specific than umbilical artery pH in predicting adverse neonatal outcome. Area under ROC (at 95th percentile) shown serum lactate is more accurate in predicting adverse neonatal outcome compared to umbilical artery pH at birth.


2021 ◽  
Author(s):  
Megumi Hoshiai ◽  
Kaori Ochiai ◽  
Yuma Tamura ◽  
Tomoki Tsurumi ◽  
Masato Terashima ◽  
...  

AbstractNeuromuscular electrical stimulation has been used to treat cardiovascular diseases and other types of muscular dysfunction. A novel whole-body neuromuscular electrical stimulation (WB-NMES) wearable device may be beneficial when combined with voluntary exercises. This study aimed to investigate the safety and effects of the WB-NMES on hemodynamics, arrhythmia, and sublingual microcirculation. The study included 19 healthy Japanese volunteers, aged 22–33 years, who were not using any medication. Electrocardiogram (ECG), echocardiography, and blood sampling were conducted before a 20-min WB-NMES session and at 0 and 10 min after termination of WB-NMES. Their tolerable maximum intensity was recorded using numeric rating scale. Arrhythmia was not detected during neuromuscular electrical stimulation or during 10 min of recovery. Blood pressure, heart rate, left ventricular ejection fraction, and diastolic function remained unchanged; however, mild mitral regurgitation was transiently observed during WB-NMES in a single male participant. A decrease in blood glucose and an increase in blood lactate levels were observed, but no changes in blood fluidity, sublingual microcirculation, blood levels of noradrenaline, or oxidative stress were shown. WB-NMES is safe and effective for decreasing blood glucose and increasing blood lactate levels without changing the blood fluidity or microcirculation in healthy people.


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