scholarly journals A Combination Approach in Inhibiting Type 2 Diabetes-Related Enzymes Using Ecklonia radiata Fucoidan and Acarbose

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1979
Author(s):  
Blessing Mabate ◽  
Chantal Désirée Daub ◽  
Samkelo Malgas ◽  
Adrienne Lesley Edkins ◽  
Brett Ivan Pletschke
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Potent Inhibitor ◽  
Cell Toxicity ◽  
Ecklonia Radiata ◽  
Synergistic Inhibition ◽  
Analysis Techniques ◽  
Ft Ir ◽  
Combination Approach

Although there are chemotherapeutic efforts in place for Type 2 diabetes mellitus (T2DM), there is a need for novel strategies (including natural products) to manage T2DM. Fucoidan, a sulphated polysaccharide was extracted from Ecklonia radiata. The integrity of the fucoidan was confirmed by structural analysis techniques such as FT-IR, NMR and TGA. In addition, the fucoidan was chemically characterised and tested for cell toxicity. The fucoidan was investigated with regards to its potential to inhibit α-amylase and α-glucosidase. The fucoidan was not cytotoxic and inhibited α-glucosidase (IC50 19 µg/mL) more strongly than the standard commercial drug acarbose (IC50 332 µg/mL). However, the fucoidan lacked potency against α-amylase. On the other hand, acarbose was a more potent inhibitor of α-amylase (IC50 of 109 µg/mL) than α-glucosidase. Due to side effects associated with the use of acarbose, a combination approach using acarbose and fucoidan was investigated. The combination showed synergistic inhibition (>70%) of α-glucosidase compared to when the drugs were used alone. The medicinal implication of this synergism is that a regimen with a reduced acarbose dose may be used, thus minimising side effects to the patient, while achieving the desired therapeutic effect for managing T2DM.

Effectiveness and side effects of thiazolidinediones for type 2 diabetes

2005 ◽  
Vol 182 (9) ◽  
pp. 492-494 ◽  
Author(s):  
Nirusha Arnold ◽  
Mark McLean ◽  
David R Chipps ◽  
N Wah Cheung
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects

scholarly journals Pseudoginsenoside F11, a Novel Partial PPARγAgonist, Promotes Adiponectin Oligomerization and Secretion in 3T3-L1 Adipocytes

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Guoyu Wu ◽  
Junyang Yi ◽  
Ling Liu ◽  
Pengcheng Wang ◽  
Zhijie Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Hormone Receptor ◽  
Adipocyte Differentiation ◽  
American Ginseng ◽  
Nuclear Hormone Receptor ◽  
Targeted Therapeutics ◽  
Panax Quinquefolium ◽  
Master Regulator

PPARγis a nuclear hormone receptor that functions as a master regulator of adipocyte differentiation and development. Full PPARγagonists, such as the thiazolidinediones (TZDs), have been widely used to treat type 2 diabetes. However, they are characterized by undesirable side effects due to their strong agonist activities. Pseudoginsenoside F11 (p-F11) is an ocotillol-type ginsenoside isolated fromPanax quinquefolium L.(American ginseng). In this study, we found that p-F11 activates PPARγwith modest adipogenic activity. In addition, p-F11 promotes adiponectin oligomerization and secretion in 3T3-L1 adipocytes. We also found that p-F11 inhibits obesity-linked phosphorylation of PPARγat Ser-273 by Cdk5. Therefore, p-F11 is a novel partial PPARγagonist, which might have the potential to be developed as a new PPARγ-targeted therapeutics for type 2 diabetes.

Abstract 234: Treatment Satisfaction Levels among Adults with Concomitant Conditions of Type 2 Diabetes Mellitus and Hypertension

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Kathleen M Fox ◽  
Susan Grandy ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Side Effects ◽  
Diabetes Medication ◽  
Medication Therapy ◽  
The Us ◽  
Medication Side

Objective: This investigation evaluated the satisfaction with therapy for adults with the concomitant conditions of type 2 diabetes mellitus (T2DM) and hypertension (HTN). Methods: Respondents to the US S tudy to H elp I mprove E arly evaluation and management of risk factors L eading to D iabetes (SHIELD) 2009 survey reported their disease conditions, current medications, and satisfaction with therapy. Respondents reporting T2DM with concomitant HTN were identified. Current medications were catalogued, as respondents referred to their prescription bottles to record the name of each medication. Therapy satisfaction was captured with 3 separate questions as satisfaction/dissatisfaction with: 1) ability of the medication to prevent or treat your condition, 2) side effects of the medication, and 3) the medication overall; and scored using a 0 (completely dissatisfied) to 5 (completely satisfied) scale for heart disease treatment and diabetes treatment, separately. Scores of 0-2 were categorized as dissatisfied, score of 3 was neutral and scores 4-5 were satisfied. Results: A total of 911 adults with T2DM and HTN reported their satisfaction with therapy. For those who were dissatisfied with their diabetes medication (n = 63), 52.6% were also dissatisfied with their heart disease medication's ability to treat their HTN, 64.5% were dissatisfied with the side effects of their heart medications, and 61.9% were dissatisfied with their heart medication overall. For those who were dissatisfied with their heart disease medication (n = 59), 74.5% were also dissatisfied with their diabetes medication's ability to treat their diabetes, 56.6% were dissatisfied with the side effects of their diabetes medication, and 66.1% were dissatisfied with their diabetes medication overall. Conclusions: Although most respondents with T2DM and HTN were satisfied with their treatment, dissatisfaction with treatment for one condition was associated with therapy dissatisfaction in the other condition. Approximately 53%-65% of respondents who were dissatisfied with their diabetes medication were also dissatisfied with their HTN medication overall and in the ability to treat the condition and medication side effects.

scholarly journals Oxidative stress in patients with type 2 diabetes mellitus treated with metformin

2017 ◽  
Vol 27 (2) ◽  
pp. 25857
Author(s):  
Samuel Selbach Dries ◽  
Bárbara Da Silveira Soares ◽  
Ana Luiza Ziulkoski ◽  
Simone Gasparin Verza ◽  
Rafael Linden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Superoxide Dismutase ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Side Effects ◽  
Diabetic Complications

*** Oxidative stress in patients with type 2 diabetes mellitus treated with metformin ***AIMS: To evaluate oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin, relating these values to its side effects, plasma levels, glycemic control, diabetic complications, lipid profile, and the influence of pharmacotherapeutic follow-up.METHODS: Patients with type 2 diabetes mellitus, on metformin and in pharmacotherapeutic follow-up for four months, were evaluated. The pharmacotherapeutic follow-up consisted in providing information and answering patients’ questions about medication and disease. In addition, administration times, dosages, and presence or absence of side effects related to the use of metformin were verified. Glycemic and lipid profile, oxidative stress (superoxide dismutase and malondialdehyde) and plasma metformin were evaluated. Pearson’s correlation and Spearman’s correlation were performed to evaluate the relationship between the variables at the beginning of the study. The independent t-test and Mann-Whitney U test were used to assess the difference between the groups with and without diabetic complications. The range of values between the beginning and  end of the study was evaluated using Student’s t-test or Wilcoxon U test. The significance level was set at 5%.RESULTS: The initial sample consisted of 49 patients aged 59±9 years with a body mass index of 29.8±5.1 kg/m2, who have had diabetes for a median time of 36 months (interquartile range of 1-240) and have been on metformin for a median time of 36 months (interquartile range of 1-180). Twenty-five patients left the study between the second and fourth meetings. Malondialdehyde levels differed between before and after pharmacotherapeutic follow-up, being positively correlated with blood glucose, glycohemoglobin, and triglyceride level, and negatively correlated with metformin and superoxide dismutase. Blood glucose, glycohemoglobin, and malondialdehyde levels increased, whereas metformin levels decreased in the group with diabetic complications, and there was a correlation between malondialdehyde and the number of diabetic complications per patient.CONCLUSIONS: In this sample of patients with type 2 diabetes mellitus treated with metformin, oxidative stress was more pronounced in those with poor glycemic control and diabetic complications.

Increasing endogenous PPARγ ligands improves insulin sensitivity and protects against diet-induced obesity without side effects of thiazolidinediones

2021 ◽  
Author(s):  
Yu-Hua Tseng ◽  
Lee-Ming Chuang ◽  
Yi-Cheng Chang ◽  
Meng-Lun Hsieh ◽  
Lun Tsou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Side Effects ◽  
Knockout Mice ◽  
Fasting Glucose ◽  
Binding Mode ◽  
Fluid Retention ◽  
Diet Induced Obesity

Abstract Insulin resistance and obesity are pivotal features of type 2 diabetes mellitus. Peroxisome proliferator-activated receptor γ (PPARγ) is a master transcriptional regulator of systemic insulin sensitivity and energy balance. The anti-diabetic drug thiazolidinediones are potent synthetic PPARγ ligands and insulin sensitizers with undesirable side effects including increased adiposity, fluid retention, and osteoporosis, which limit their clinical use. We and others have proved that 15-keto-PGE2 is an endogenous natural PPARγ ligand. 15-keto-PGE2 is catalyzed by prostaglandin reductase 2 (PTGR2) to become inactive metabolites. We found that 15-keto-PGE2 level is increased in Ptgr2 knockout mice. Ptgr2 knockout mice were protected from diet-induced obesity, insulin resistance, and hepatic steatosis without fluid retention nor reduced bone mineral density. Diet-induced obese mice have drastically reduced 15-keto-PGE2 levels compared to lean mice. Administration of 15-keto-PGE2 markedly improved insulin sensitivity and prevented diet-induced obesity in mice. We demonstrated that 15-keto-PGE2 activates PPARγ through covalent binding to its cysteine 285 residue at helix 3, which restrained its binding pocket between helix 3 and β-sheets of the PPARγ ligand binding domain. This binding mode differs from the helix12-dependent binding mode of thiazolidinediones. We further identified a small-molecule PTGR2 inhibitor BPRPT245, which interferes the interaction between the substrate-binding sites of PTGR2 and 15-keto-PGE2. BPRPT245 increased 15-keto-PGE2 concentration, activated PPARγ, and promoted glucose uptake in adipocytes. BPRPT245 also prevented diet-induced obesity, improved insulin sensitivity and glucose tolerance, lowers fasting glucose without fluid retention and osteoporosis. In humans, reduced serum 15-keto-PGE2 levels were observed in patients with type 2 diabetes compared with controls. Furthermore, serum 15-keto-PGE2 levels correlate inversely with insulin resistance and fasting glucose in non-diabetic humans. In conclusion, we identified a new therapeutic approach to improve insulin sensitivity and protect diet-induced obesity through increasing endogenous natural PPARγ ligands without side effects of thiazolidinediones.

scholarly journals Investigation on the Enzymatic Profile of Mulberry Alkaloids by Enzymatic Study and Molecular Docking

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1776 ◽  
Author(s):  
Zhihua Liu ◽  
Ying Yang ◽  
Wujun Dong ◽  
Quan Liu ◽  
Renyun Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Molecular Docking ◽  
Side Effects ◽  
Inhibitory Effect ◽  
Active Ingredients ◽  
Wide Range ◽  
Consensus Score

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.

Psylog, an EPA smartphone application to prevent antipsychotic side-effects

2014 ◽  
Vol 29 (S3) ◽  
pp. 672-673
Author(s):  
O. Andlauer ◽  
M. Rojnic-Kuzman
Keyword(s):  
Quality Of Life ◽  
Type 2 Diabetes ◽  
Side Effects ◽  
Psychiatric Care ◽  
Smartphone Application ◽  
Psychoeducational Intervention ◽  
Antipsychotic Medications ◽  
Antipsychotic Side Effects

Antipsychotic medications are used to treat a significant number of psychiatric disorders, such as schizophrenia or bipolar disorder, which have a significant impact on overall disability in Europe. Although these drugs have documented efficacy, they are also associated with side-effects such as drowsiness, weight gain, type 2 diabetes, or extrapyramidal symptoms [1]. These contribute to increasing overall morbidity and mortality [2], reduced quality of life, and can push patients to stop their medications. This often leads to relapse, and the need for a new hospital admission, which is detrimental to the patient, and create extra costs for the society. However, the monitoring of side-effects is rarely carried out in a standardized way in daily clinical practice. Smartphones are an acceptable and easy to use tool available to patients with schizophrenia [3]. The aim of the mPIVAS (mHealth psychoeducational intervention versus antipsychotic-induced side effects) project is to develop an effective and innovative smartphone application that can be used by psychiatrists and patients in order to monitor medications’ side-effects. The European Psychiatric Association (EPA) is involved in this project with the objective to develop this application in 6 languages. Part of the project includes training European early careers psychiatrists to the use Psylog and helping them to spread information about this new project in their own country, by organising local and national cascade courses. We expect an improvement in psychiatric care in all involved institutions through the education of employees, a better implication of patients in their disease, and an improved monitoring of antipsychotic side-effects.

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