Antidiabetic properties of fenugreek and its interaction with glibenclamide in an animal model of type 2 diabetes mellitus
Ontology highlight
ABSTRACT:
SUBMITTER: Rania M Magadmi
PROVIDER: S-BSST140 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The global incidence of diabetes mellitus (DM) is increasing. Types 1 and 2 DM are associated with declining β-cell function. Verapamil (50% S-verapamil and 50% R-verapamil) can treat DM by downregulating thioredoxin-interacting protein (TXNIP), which induces islet β-cell apoptosis. However, it may also induce cardiovascular side effects as S-verapamil is negatively inotropic. In contrast, R-verapamil only weakly induces adverse cardiac effects. In this study, we aimed to determine the antidiabetic efficacy and cardiovascular safety of R-verapamil. We examined R- and S-verapamil binding through in vitro studies. Streptozotocin-induced type 1 and db/db type 2 DM mouse models were used to assess the antidiabetic efficacy of verapamil. IL-6, blood glucose (BG), Txnip expression, and β-cells were evaluated in streptozotocin-induced diabetic mice, while body weight, BG, and serum insulin were measured in the db/db mice. In the type 1 DM study, 100 mg/kg/day R-verapamil and racemic verapamil lowered BG, downregulated Txnip expression, and reduced β-cell apoptosis. In the type 2 DM study, the optimal R-verapamil dosage was 60 mg/kg/day and it lowered BG and raised serum insulin. However, efficacy did not increase with R-verapamil dosage. R-verapamil combined with metformin/acarbose improved BG and serum insulin more effectively than metformin/acarbose alone or verapamil combined with acarbose. R-verapamil had weaker cardiovascular side effects than S-verapamil. R-verapamil was 9.0× and 3.4× less effective than S-verapamil at inhibiting atrial inotropy and ileal contractility, respectively. It was also 8.7× weaker than S-verapamil as an agonist of somatostatin receptor type 2 (SSTR2), inhibiting ileal neurogenic contraction. Hence, R-verapamil may be an optimal DM treatment as it is safe, improves glycemic control, and preserves β-cell function both as monotherapy and in combination with metformin or acarbose. R-Verapamil has potential for delaying or arresting DM progression and improving patients' quality of life.
| S-EPMC8345870 | biostudies-literature
Project description:BackgroundElevated homocysteine (Hc) levels have a well-established and clear causal relationship to epithelial damage leading to coronary artery disease. Furthermore, it is strongly associated with other metabolic syndrome variables, such as hypertension, which is correlated with type II diabetes mellitus (T2DM). Studies on T2DM in relation to Hc levels have shown both positive and negative associations. The aim of the present study is to examine the relationship between Hc levels and risk of T2DM in the Lebanese population.MethodsWe sought to identify whether Hc associates positively or negatively with diabetes in a case-control study, where 2755 subjects enrolled from patients who had been catheterized for coronary artery diagnosis and treatment. We further sought to identify whether the gene variant MTHFR 667C>T is associated with T2DM, and how Hc and MTHFR 667C>T also impact other correlates of T2DM, including the widely used diuretics in this study population.ResultsWe found that Hc levels were significantly reduced among subjects with diabetes compared to those without diabetes when adjusted for all potential confounders (OR 0.640; 95% CI [0.44-0.92]; p = 0.0200). The associations between Hc levels and other variates contradicted the result: hypertension associates positively with high Hc levels, and with T2DM. The MTHFR 667C>T only associated significantly with high Hc levels.ConclusionThese results suggest population-specific variations among a range of mechanisms that modulate the association of Hc and T2DM, providing a probe for future studies.
| S-EPMC5359933 | biostudies-literature
Project description:Heart failure is the most common comorbidity of diabetes. The incidence of heart failure in patients with diabetes is about 9%-22%, which is four times higher Than that in patients without diabetes. Heart failure and diabetes are collectively associated with increased morbidity and mortality compared to either condition alone. Several epidemiological studies have demonstrated an increased risk of heart failure in patients with diabetes; moreover, poor glycemic control accounts for the increased risk of heart failure. At present, several oral (metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, etc.) as well as injectable (insulins, glucagon-like peptide 1 receptor agonists) antidiabetic agents are available. However, optimal treatment strategy to achieve adequate glycemic control in patients with type 2 diabetes mellitus (T2DM) and heart failure has not been well studied. In the view of rising prevalence of heart failure in patients with diabetes mellitus, clinicians need to understand the potential implications of antidiabetic agents in patients with heart failure. A group of experts from across India were involved in a consensus meeting in Pondicherry during the National Insulin Summit in November 2015. They evaluated agents currently available for the treatment of diabetes looking at existing scientific evidence relevant to each class of therapy. In addition, the existing guidelines and prescribing literature available with all these agents were also reviewed. Findings from the expert evaluations were then factored into the national context incorporating personal experience and common clinical practices in India. The purpose of this consensus document is to assist the clinicians while treating patients with T2DM and heart failure.
| S-EPMC5477452 | biostudies-other
Project description:This study was performed to investigate the effect of gastric banding surgery on the improvement of glycated hemoglobin (HbA1c) of morbidly obese (MO) patients with type 2 diabetes mellitus (T2DM) with the consideration that obesity was associated with insulin resistance and T2DM. We retrospectively reviewed the medical records of 38 MO with T2DM patients and 50 MO patients. Pre-surgery and post-surgery data were analyzed a year later. The medical data from these patients, including sex, age, height, weight, body composition, HbA1c, triglyceride, total cholesterol, aspartate transaminase (AST), and alanine transaminase (ALT) were measured. There were significant reductions of body weight and body mass index (BMI), body fat, body fat percentage, waist-hip ratio, visceral fat, and obesity in each group before and after gastric banding surgery. Results of AST, ALT, and HbA1c had significant reductions in each group. For HbA1c, treatment rate was 71% in the MO group with T2DM with significant reduction of 22.8%. It is thought that a gastric banding surgery is one of the breakthrough methods not only for weight loss but also for the prevention of complication of the obese patients with T2DM. Thus, gastric banding surgery could be effective in controlling HbA1c in obese patients with type 2 diabetes mellitus.
| S-EPMC5539214 | biostudies-other
Project description:AIM:To assess prescribing practices of noninsulin antidiabetic drugs (NIADs) in T2DM with several major contraindications according to prescribing information or clinical guidelines: renal failure, heart failure, liver dysfunction, or history of bladder cancer. METHODS:Cross-sectional, descriptive, multicenter study. Electronic medical records were retrieved from all T2DM subjects who attended primary care centers pertaining to the Catalan Health Institute in Catalonia in 2013 and were pharmacologically treated with any NIAD alone or in combination. RESULTS:Records were retrieved from a total of 255,499 pharmacologically treated patients. 78% of patients with some degree of renal impairment (glomerular filtration rate (GFR) < 60 mL/min) were treated with metformin and 31.2% with sulfonylureas. Even in the event of severe renal failure (GFR < 30 mL/min), 35.3% and 22.5% of patients were on metformin or sulfonylureas, respectively. Moreover, metformin was prescribed to more than 60% of patients with moderate or severe heart failure. CONCLUSION:Some NIADs, and in particular metformin, were frequently used in patients at high risk of complications when they were contraindicated. There is a need to increase awareness of potential inappropriate prescribing and to monitor the quality of prescribing patterns in order to help physicians and policymakers to yield better clinical outcomes in T2DM.
| S-EPMC4736814 | biostudies-literature
Project description:Background:Glucose variability (GV) is considered an important factor for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). High GV causes endothelial dysfunction and increased oxidative stress. Dipeptidyl peptidase-4 (DPP-4) inhibitors may improve endothelial function and decrease GV. The aim of this study was to investigate the effects of vildagliptin, a DPP-4 inhibitor, compared with glibenclamide in GV and endothelial function in patients with T2DM and arterial hypertension. Methods:This is a prospective, randomized, open and drug-controlled study. Fifty patients older than 35 years with T2DM and hypertension without CVD were randomized to receive vildagliptin (n=25) or glibenclamide (n=25), both in added-on metformin. Laboratory tests and analysis of endothelial function were performed before and 12 weeks after treatment. Endothelial function, defined by reactive hyperemia index (RHI), was analyzed by peripheral artery tonometry (endo-PAT2000). GV was evaluated by capillary glucose with intermittent monitoring device, six measurements per day, for three days, before and after treatment. The median of standard deviation (SD) of mean blood glucose (MBG) was used to evaluate GV. Results:GV decreased in the vildagliptin group (35.2 to 30.7, P=0.037) but did not change with glibenclamide (37.6 to 37.5, P=0.765). Glycated hemoglobin was similar in both groups. MBG decreased only in glibenclamide group, without difference with vildagliptin group (P=0.374). There were no changes in the RHI in both groups and there was no correlation between GV and RHI (P=0.658). Conclusion:Vildagliptin reduces GV; however, the action on endothelial function was not demonstrated. In addition, there was no correlation between GV and endothelial function.
| S-EPMC7508021 | biostudies-literature
Project description:Understanding the gut microbiota in metabolic disorders, including type 2 diabetes mellitus (T2DM), is now gaining importance due to its potential role in disease risk and progression. We previously established a zebrafish model of T2DM, which shows glucose intolerance with insulin resistance and responds to anti-diabetic drugs. In this study, we analysed the gut microbiota of T2DM zebrafish by deep sequencing the 16S rRNA V3-V4 hypervariable regions, and imputed a functional profile using predictive metagenomic tools. While control and T2DM zebrafish were fed with the same kind of feed, the gut microbiota in T2DM group was less diverse than that of the control. Predictive metagenomics profiling using PICRUSt revealed functional alternation of the KEGG pathways in T2DM zebrafish. Several amino acid metabolism pathways (arginine, proline, and phenylalanine) were downregulated in the T2DM group, similar to what has been previously reported in humans. In summary, we profiled the gut microbiome in T2DM zebrafish, which revealed functional similarities in gut bacterial environments between these zebrafish and T2DM affected humans. T2DM zebrafish can become an alternative model organism to study host-bacterial interactions in human obesity and related diseases.
| S-EPMC6351536 | biostudies-literature
Project description:Background. Metformin is a widely accepted first-line pharmacotherapy for patients with type 2 diabetes mellitus (T2DM). Treatment of T2DM with glibenclamide, saxagliptin, or one of the other second-line treatment agents is recommended when the first-line treatment (metformin) cannot control the disease. However, there is little evidence on the additional cost and cost-effectiveness of adding second-line drugs. Therefore, this study aimed to estimate the cost-effectiveness of saxagliptin and glibenclamide as second-line therapies added to metformin compared with metformin only in T2DM in Ethiopia. Methods. This cost-effectiveness study was conducted in Ethiopia using a mix of primary data on cost and best available data from the literature on the effectiveness. We measured the interventions' cost from the providers' perspective in 2019 US dollars. We developed a Markov model for T2DM disease progression with five health states using TreeAge Pro 2020 software. Disability-adjusted life year (DALY) was the health outcome used in this study, and we calculated the incremental cost-effectiveness ratio (ICER) per DALY averted. Furthermore, one-way and probabilistic sensitivity analysis were performed. Results. The annual unit cost per patient was US$70 for metformin, US$75 for metformin + glibenclamide, and US$309 for metformin + saxagliptin. The ICER for saxagliptin + metformin was US$2259 per DALY averted. The ICER results were sensitive to various changes in cost, effectiveness, and transition probabilities. The ICER was driven primarily by the higher cost of saxagliptin relative to glibenclamide. Conclusion. Our study revealed that saxagliptin is not a cost-effective second-line therapy in patients with T2DM inadequately controlled by metformin monotherapy based on a gross domestic product per capita per DALY averted willingness-to-pay threshold in Ethiopia (US$953).
| S-EPMC8111283 | biostudies-literature
Project description:In patients with diabetes mellitus (DM), impairments of circadian rhythms, including the sleep-wake cycle, blood pressure, and plasma melatonin concentrations, are frequently observed. Animal models of DM are also reported to show aberrant circadian rhythms. However, the changes in the circadian rhythms of plasma soluble substances, including melatonin, in diabetic animals are controversial. In the present study, we investigated the circadian rhythms of spontaneous locomotor activity, metabolic parameters (plasma glucose, triglyceride, and total cholesterol), and plasma melatonin concentrations in Spontaneously Diabetic Torii (SDT) fatty rats, a novel animal model of type 2 DM. Although SDT fatty rats exhibited low locomotor activity in the dark phase, no phase shifts were observed. The circadian variations of plasma metabolic parameters were more apparent in the SDT fatty rats compared with control Sprague-Dawley (SD) rats. The circadian rhythms of plasma melatonin concentrations were significantly impaired in SDT fatty rats. To get an insight into the mechanism underlying the impaired melatonin secretion in SDT fatty rats, the expression of arylalkylamine N-acetyltransferase (Aanat) and acetylserotonin O-methyltransferase (Asmt) mRNA, which encode the rate-limiting enzymes for melatonin synthesis, was investigated in the pineal gland. There were no significant differences in Aanat and Asmt expression between the control SD and SDT fatty rats. These results suggest that SDT fatty rats show impaired circadian rhythms and dysregulated melatonin secretion.
| S-EPMC6174757 | biostudies-other
Project description:Incretin-based therapy is now a prevalent treatment option for patients with type 2 diabetes mellitus (T2DM). It has been associated with considerably good results in the management of hyperglycemia with cardiac or nephron-benefits. For this reason, it is recommended for individuals with cardiovascular diseases in many clinical guidelines. As an incretin hormone, glucagon-like peptide-1 (GLP-1) possesses multiple metabolic benefits such as optimizing energy usage, maintaining body weight, ? cell preservation, and suppressing neurodegeneration. However, recent studies indicate that oral antidiabetic medications interact with endogenous or exogenous GLP-1. Since these drugs are transported to distal intestine portions, there are concerns whether these oral drugs directly stimulate intestinal L cells which release GLP-1, or whether they do so via indirect inhibition of the activity of dipeptidyl peptidase-IV (DPP-IV). In this review, we discuss the metabolic relationships between oral antihyperglycemic drugs from the aspect of gut, microbiota, hormones, ? cell function, central nervous system, and other cellular mechanisms.
| S-EPMC7320283 | biostudies-literature