scholarly journals Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6907
Author(s):  
Guoxia Ji ◽  
Qinghua Guo ◽  
Qidi Xue ◽  
Ruifang Kong ◽  
Shiben Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Pancreatic Beta Cells ◽  
Drug Candidate ◽  
Dependent Manner ◽  
Promising Target ◽  
Reduce Blood Glucose ◽  
Glucagon Like Peptide 1 ◽  
The Stability

GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood glucose. In this study, a series of novel GPR120 agonists were designed and synthesized to improve the stability and hydrophilicity of the phenylpropanoic acid GPR120 agonist TUG-891. Compound 11b showed excellent GPR120 agonistic activity and pharmacokinetic properties, and could reduce the blood glucose of normal mice in a dose-dependent manner. In addition, no hypoglycemic side effects were observed even at a dose of 100 mg/kg. Moreover, 11b showed good anti-hyperglycemic effects in diet-induced obese (DIO) mice. Molecular simulation illustrated that compound 11b could enter the active site of GPR120 and interact with ARG99. Taken together, the results indicate that compound 11b might be a promising drug candidate for the treatment of T2DM.

scholarly journals Treatment of type 2 diabetes: the stability of the effectiveness of hypoglycemic medications

2016 ◽  
Vol 13 (3) ◽  
pp. 32-36
Author(s):  
Tat'yana Morgunova ◽  
Valentin Fadeev
Keyword(s):  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Original Research ◽  
Dipeptidyl Peptidase 4 ◽  
Sodium Glucose Cotransporter ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Stability

This article is dedicated to the problem of glycaemic durability of drugs used in treatment of type 2 diabetes. The results of studies comparing durability of glycemic control as monotherapy or in combination of metformin with different drugs: dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sulfonylurea, inhibitors of sodium-glucose cotransporter-2 are shown. The article discusses the results of original research and meta-analysis.

scholarly journals Herbal constituent sequoyitol improves hyperglycemia and glucose intolerance by targeting hepatocytes, adipocytes, and β-cells

2012 ◽  
Vol 302 (8) ◽  
pp. E932-E940 ◽  
Author(s):  
Hong Shen ◽  
Mengle Shao ◽  
Kae Won Cho ◽  
Suqing Wang ◽  
Zheng Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Intolerance ◽  
Insulin Signaling ◽  
Glucose Production ◽  
Water Soluble ◽  
Β Cells ◽  
Β Cell ◽  
Reduce Blood Glucose

The prevalence of insulin resistance and type 2 diabetes increases rapidly; however, treatments are limited. Various herbal extracts have been reported to reduce blood glucose in animals with either genetic or dietary type 2 diabetes; however, plant extracts are extremely complex, and leading compounds remain largely unknown. Here we show that 5- O-methyl- myo-inositol (also called sequoyitol), a herbal constituent, exerts antidiabetic effects in mice. Sequoyitol was chronically administrated into ob/ob mice either orally or subcutaneously. Both oral and subcutaneous administrations of sequoyitol decreased blood glucose, improved glucose intolerance, and enhanced insulin signaling in ob/ob mice. Sequoyitol directly enhanced insulin signaling, including phosphorylation of insulin receptor substrate-1 and Akt, in both HepG2 cells (derived from human hepatocytes) and 3T3-L1 adipocytes. In agreement, sequoyitol increased the ability of insulin to suppress glucose production in primary hepatocytes and to stimulate glucose uptake into primary adipocytes. Furthermore, sequoyitol improved insulin signaling in INS-1 cells (a rat β-cell line) and protected INS-1 cells from streptozotocin- or H2O2-induced injury. In mice with streptozotocin-induced β-cell deficiency, sequoyitol treatments increased plasma insulin levels and decreased hyperglycemia and glucose intolerance. These results indicate that sequoyitol, a natural, water-soluble small molecule, ameliorates hyperglycemia and glucose intolerance by increasing both insulin sensitivity and insulin secretion. Sequoyitol appears to directly target hepatocytes, adipocytes, and β-cells. Therefore, sequoyitol may serve as a new oral diabetes medication.

Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes

2004 ◽  
Vol 32 (3) ◽  
pp. 848-851 ◽  
Author(s):  
Juris J. Meier ◽  
Dirk Weyhe ◽  
Mark Michaely ◽  
Metin Senkal ◽  
Volker Zumtobel ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Major Surgery ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Insulin secretion defects in liver cirrhosis can be reversed by glucagon-like peptide-1

2000 ◽  
Vol 164 (1) ◽  
pp. 13-19 ◽  
Author(s):  
EG Siegel ◽  
A Seidenstucker ◽  
B Gallwitz ◽  
F Schmitz ◽  
A Reinecke-Luthge ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Liver Cirrhosis ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Dependent Manner ◽  
Isolated Pancreatic Islets ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Liver cirrhosis is often accompanied by a disturbed carbohydrate metabolism similar to type 2 diabetes. To investigate the severity of the defect in insulin secretion in this form of diabetes, we measured insulin release from isolated pancreatic islets of rats with CCl(4)-phenobarbital-induced liver cirrhosis. Cirrhosis was confirmed by clinical signs, elevated liver enzymes and histology. Fasting venous plasma glucose concentrations were equal in rats with liver cirrhosis and in controls. Plasma insulin and glucagon concentrations were significantly greater (P<0.01) in cirrhotic rats than in control animals. Glucose (16.7 mM)-induced stimulation of insulin release from pancreatic islets revealed a twofold increase in control and cirrhotic rats. Basal and stimulated insulin secretion, however, were significantly lower in cirrhotic animals. The incretin hormone, glucagon-like peptide-1 (GLP-1), has therapeutic potential for the treatment of type 2 diabetes. Therefore, islets from control and cirrhotic animals were incubated with GLP-1 in concentrations from 10(-)(11) to 10(-)(6) M. GLP-1 stimulated insulin release in a concentration-dependent manner. In islets from cirrhotic rats, basal and stimulated insulin secretion was blunted compared with controls. These data show that the hyperinsulinemia observed in liver cirrhosis is not due to an increase of insulin secretion from islets, but could be explained by decreased hepatic clearance of insulin. GLP-1 may ameliorate diabetes in patients with liver cirrhosis.

Lixisenatide: A New Daily GLP-1 Agonist for Type 2 Diabetes Management

2017 ◽  
Vol 51 (5) ◽  
pp. 401-409 ◽  
Author(s):  
Delilah McCarty ◽  
Megan Coleman ◽  
Cassie L. Boland
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Gastric Emptying ◽  
Diabetes Management ◽  
Human Subjects ◽  
Data Extraction ◽  
Postprandial Blood Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of the glucagon-like peptide-1 receptor agonist (GLP-1RA), lixisenatide, in the treatment of type 2 diabetes mellitus. Data Sources: A PubMed (1966-2016) search was conducted using the following keywords: lixisenatide, AVE0010, glucagon-like peptide-1 agonist, and type 2 diabetes. References were reviewed to identify additional sources. Study Selection and Data Extraction: Articles written in English were included if they evaluated the pharmacology, pharmacokinetics, efficacy, or safety of lixisenatide in human subjects. Data Synthesis: Lixisenatide lowers blood glucose through a glucose-dependent increase in insulin release from pancreatic β-cells and a decreased release of glucagon from pancreatic α-cells. Additionally, lixisenatide delays gastric emptying and increases satiety. Lixisenatide has been studied head to head against exenatide and insulin glulisine. It has also been studied as monotherapy and in combination with metformin, sulfonylureas, pioglitazone, and insulin glargine. In the GetGoal clinical trial series, lixisenatide resulted in a hemoglobin A1C reduction of 0.6% to 1% and a reduction in body weight of 0.2 to 2.96 kg. The adverse effect profile of lixisenatide was consistent with that of other GLP-1RAs, with nausea, vomiting, and diarrhea most commonly reported. Conclusion: Lixisenatide provides an additional GLP-1RA option, which may have more postprandial blood glucose-lowering effects than the other agents in the class because of its shorter half-life and effects on delaying gastric emptying.

scholarly journals Molecular Docking of Mangostin and Sinensetin Derivatives on SUR1-Pancreatic KATP Channel Target as Antidiabetic

2021 ◽  
Vol 8 (3) ◽  
pp. 271
Author(s):  
Intan Kris Prasetyanti ◽  
Sukardiman Sukardiman ◽  
Suharjono Suharjono
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Docking ◽  
Blood Glucose ◽  
Katp Channel ◽  
The Body ◽  
Discovery Studio ◽  
Reduce Blood Glucose ◽  
Macromolecular Binding ◽  
Complex Chronic Disease

Background: Diabetes Mellitus (DM) is a complex chronic disease characterized by increased blood glucose. The incidence of this disease is rising, especially type 2 diabetes which is caused by insulin resistance in the body. SUR1-Pancreatic KATP Channel is a receptor as an antidiabetic target because its inhibition process can increase insulin production so that it can reduce blood glucose in people with type 2 diabetes. Objective: This study aims to identify the in-silico activity of the SUR1-Pancreatic KATP Channel macromolecules. Methods: Identification of macromolecular binding sites using Protein Plus software, then carried out molecular docking using AutoDock software, where the formed molecular interactions are further identified using the BIOVIA Discovery Studio software. Results: After determining the macromolecular binding site, the RMSD value was 1.253, allowing for further molecular docking. Molecular docking showed that the Ligands of mangostin (α, β, γ-mangostin) and sinensetin derivatives had a good affinity, namely α-mangostin -6,31 kcal/mol; β-mangostin -5.78 kcal/mol; γ-mangostin -6.17 kcal/mol and sinensetin -4.75 kcal/mol. Conclusion: The affinity sequence in the docking process for the SUR1 KATP channel macromolecules is α-mangostin > γ-mangostin > β-mangostin > sinensetin. The highest affinity for the docking process on the macromolecule SUR1 KATP channel was α-mangostin with a value of ΔG -6.31 kcal/mol Ki 23.65 μM.

Immediate effect of a meditation technique on blood glucose, state anxiety and relaxation in patients with type 2 diabetes: a pilot randomized crossover study

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Xu Wen ◽  
Apar Avinash Saoji ◽  
Kashinath Metri ◽  
Sriloy Mohanty ◽  
Venugopal Vijayakumar
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
State Anxiety ◽  
Fasting Blood Glucose ◽  
Subjective Feeling ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Meditation Technique ◽  
Reduce Blood Glucose

Abstract Objectives Type 2 Diabetes Mellitus (T2DM) is a major burden on global health and economy. Various Yogic techniques are found to be beneficial in the management of T2DM. Mind Sound Resonance Technique (MSRT) is one of the yoga-based meditation techniques observed to be effective in clinical settings. Methods Thirty-two patients with T2DM were randomized to either MSRT or supine rest (SR) sessions on two separate days separated by a washout period of one day. Fasting blood glucose levels were measured before and immediately after the sessions. State anxiety and subjective feeling of relaxation were assessed using Spielberg’s state anxiety inventory (STAI) and Visual Analogue Scale (VAS) respectively. Results There were significant differences between MSRT and SR groups in fasting blood glucose (p=0.019), STAI scores (p<0.001) and subjective relaxation (p<0.001). Within group analyses revealed significant reductions (p<0.001) in fasting blood glucose and STAI scores, along with an increase in subjective relaxation following the practice of MSRT, whereas, non-significant changes were found following the SR session. Conclusions A single session of MSRT was found to reduce blood glucose levels and state anxiety along with enhanced relaxation when compared to SR.

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