scholarly journals Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions

Redox Biology ◽  
2020 ◽  
Vol 34 ◽  
pp. 101517 ◽  
Author(s):  
Nadezda Apostolova ◽  
Francesca Iannantuoni ◽  
Aleksandra Gruevska ◽  
Jordi Muntane ◽  
Milagros Rocha ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mechanisms Of Action

Proglucagon-Derived Peptides: Mechanisms of Action and Therapeutic Potential

Physiology ◽  
2005 ◽  
Vol 20 (5) ◽  
pp. 357-365 ◽  
Author(s):  
Elaine M Sinclair ◽  
Daniel J. Drucker
Keyword(s):  
Type 2 Diabetes ◽  
Human Disease ◽  
Clinical Relevance ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Receptor Antagonists ◽  
Glucagon Receptor ◽  
Receptor Agonists ◽  
Glucagon Like Peptide

Glucagon is used for the treatment of hypoglycemia, and glucagon receptor antagonists are under development for the treatment of type 2 diabetes. Moreover, glucagon-like peptide (GLP)-1 and GLP-2 receptor agonists appear to be promising therapies for the treatment of type 2 diabetes and intestinal disorders, respectively. This review discusses the physiological, pharmacological, and therapeutic actions of the proglucagon-derived peptides, with an emphasis on clinical relevance of the peptides for the treatment of human disease.

scholarly journals Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin

2016 ◽  
Vol 101 (4) ◽  
pp. 1798-1806 ◽  
Author(s):  
Anna Vanderheiden ◽  
Lindsay B. Harrison ◽  
Jeremy T. Warshauer ◽  
Beverley Adams-Huet ◽  
Xilong Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Treatment ◽  
Glycosylated Hemoglobin ◽  
Challenge Test ◽  
Glucagon Secretion ◽  
Mechanisms Of Action ◽  
High Dose ◽  
C Peptide

Abstract Context: The mechanisms of action of incretin mimetics in patients with long-standing type 2 diabetes (T2D) and high insulin requirements have not been studied. Objective: To evaluate changes in β-cell function, glucagon secretion, and fat distribution after addition of liraglutide to high-dose insulin. Design: A single-center, randomized, double-blind, placebo-controlled trial. Setting: University of Texas Southwestern and Parkland Memorial Hospital clinics. Patients: Seventy-one patients with long-standing (median, 17 years) T2D requiring high-dose insulin treatment (>1.5 U/kg/d; average, 2.2 ± 0.9 U/kg/d). Intervention: Patients were randomized to liraglutide 1.8 mg/d or matching placebo for 6 months. Main Outcome Measures: We measured changes in insulin and glucagon secretion using a 4-hour mixed-meal challenge test. Magnetic resonance-based techniques were used to estimate sc and visceral fat in the abdomen and ectopic fat in the liver and pancreas. Results: Glycosylated hemoglobin improved significantly with liraglutide treatment, with an end-of-trial estimated treatment difference between groups of −0.9% (95% confidence interval, −1.5, −0.4%) (P = .002). Insulin secretion improved in the liraglutide group vs placebo, as measured by the area under the curve of C-peptide (P = .002) and the area under the curves ratio of C-peptide to glucose (P = .003). Insulin sensitivity (Matsuda index) and glucagon secretion did not change significantly between groups. Liver fat and sc fat decreased in the liraglutide group vs placebo (P = .0006 and P = .01, respectively), whereas neither visceral nor pancreatic fat changed significantly. Conclusions: Treatment with liraglutide significantly improved insulin secretion, even in patients with long-standing T2D requiring high-dose insulin treatment. Liraglutide also decreased liver and sc fat, but it did not alter glucagon secretion.

scholarly journals Safety and Mode of Action of Diabetes Medications in comparison with 5-Aminolevulinic Acid (5-ALA)

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Peter R. Rehani ◽  
Hanaa Iftikhar ◽  
Motowo Nakajima ◽  
Tohru Tanaka ◽  
Zaid Jabbar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Amino Acid ◽  
Diabetes Management ◽  
Aminolevulinic Acid ◽  
Mechanisms Of Action ◽  
Mitochondrial Functions ◽  
Porphyrin Synthesis

5-Aminolevulinic acid (5-ALA) is a delta amino acid naturally present in every living cell of the human body. 5-ALA is produced in the mitochondria as the first product of the porphyrin synthesis pathway and composes heme; exogenously supplemented 5-ALA helps in upregulating mitochondrial functions. Mitochondrial dysfunction has been associated with the pathophysiology of diabetes mellitus. Thus, in this review, we evaluate the mechanisms of action and adverse effects of common medications used to treat type 2 diabetes mellitus as well as 5-ALA including its mechanism and possible use in diabetes management.

scholarly journals Cellular and Molecular Mechanisms of Metformin Action

2020 ◽  
Author(s):  
Traci E LaMoia ◽  
Gerald I Shulman
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Low Cost ◽  
Mechanisms Of Action ◽  
Hepatic Gluconeogenesis ◽  
Glucose Lowering ◽  
Dependent Mechanism

Abstract Metformin is a first-line therapy for the treatment of type 2 diabetes, due to its robust glucose-lowering effects, well-established safety profile, and relatively low cost. While metformin has been shown to have pleotropic effects on glucose metabolism, there is a general consensus that the major glucose-lowering effect in patients with type 2 diabetes is mostly mediated through inhibition of hepatic gluconeogenesis. However, despite decades of research, the mechanism by which metformin inhibits this process is still highly debated. A key reason for these discrepant effects is likely due to the inconsistency in dosage of metformin across studies. Widely studied mechanisms of action, such as complex I inhibition leading to AMPK activation, have only been observed in the context of supra-pharmacological (>1 mM) metformin concentrations, which do not occur in the clinical setting. Thus, these mechanisms have been challenged in recent years and new mechanisms have been proposed. Based on the observation that metformin alters cellular redox balance, a redox-dependent mechanism of action has been described by several groups. Recent studies have shown that clinically relevant (50-100 μM) concentrations of metformin inhibit hepatic gluconeogenesis in a substrate-selective manner both in vitro and in vivo, supporting a redox-dependent mechanism of metformin action. Here, we review the current literature regarding metformin’s cellular and molecular mechanisms of action.

Mechanisms of Action of Metformin in Type 2 Diabetes and Associated Complications: An Overview

2008 ◽  
Vol 8 (13) ◽  
pp. 1343-1354 ◽  
Author(s):  
Sonia Correia ◽  
Cristina Carvalho ◽  
Maria Santos ◽  
Raquel Seica ◽  
Catarina Oliveira ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mechanisms Of Action

scholarly journals Anti-diabetic Agents and the Potentials for Reducing Cardiovascular Risks in Type-2 Diabetes Mellitus

2021 ◽  
Vol 7 (3) ◽  
pp. 208-226
Author(s):  
IU Ezeani ◽  
A Eregie ◽  
AE Ohwovoriole
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Mechanisms Of Action ◽  
Sglt2 Inhibitors ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Outcome Trials ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Recent reports from Cardiovascular Outcome Trials (CVOTs) revealed that some newer anti-diabetic drugs impact Major Adverse Cardiovascular Events (MACE). These medications include the Sodium-Glucose Co-Transporter (SGLT2) inhibitors and the Glucagon-like Peptide-1 (GLP-1) receptor agonists. There is a need for a review of the mechanisms of action of these drugs, in addition to their glucose-lowering effects and CV benefits. This review paper aims to explore the cardio-protective effects and CV risks of anti-diabetic medications, their mechanisms of action and the CV benefits evidenced by CVOTs. Using internet search, with search items such as Type 2 Diabetes mellitus, cardiovascular risk factors, cardiovascular outcome trials, major adverse cardiovascular events, sodium-glucose transporter-2 inhibitors, glucagon-like peptide-1 receptor agonist, the Google Scholar, EMBASE, PubMed, Medline, Web MD, and Scopus were checked for various relevant published articles. Analyses of the results of multiple CVOTs from various parts of the world were considered. These CVOTs were reviewed to assess the role of anti-diabetic agents in reducing cardiovascular risk in patients with T2DM. The SGLT2 inhibitors and GLP1 agonists were found to be beneficial in lowering MACE when compared with placebo. This is in addition to their anti-hyperglycaemic benefits. In conclusion, SGLT2 inhibitors and GLP-1 agonists confer dramatic beneficial CV risk reduction on patients with T2DM, as shown by the various CVOTs. This is in addition to their anti-hyperglycaemic effects. This remarkable benefit justifies the need by various guidelines to adopt them as second line agents to metformin in managing patients with T2DM.

scholarly journals Mechanisms of Action of Metformin

2021 ◽  
Author(s):  
Samira Abdulla Mahmood
Keyword(s):  
Type 2 Diabetes ◽  
Antioxidant Enzymes ◽  
Insulin Action ◽  
Fat Metabolism ◽  
Mechanisms Of Action ◽  
Clinical Applications ◽  
First Choice ◽  
Hepatic Glucose ◽  
Glucose Output

Metformin is the first-choice drug for treatment of type 2 diabetes notably those associated with obesity. It does not only reduce hyperglycemia, but also possesses pleiotropic effects opening the pave for numerous potential clinical applications. In this chapter we illustrate the various mechanisms of metformin action in reduction of hepatic glucose output, improvement of insulin action, restoration of fat metabolism and gut microbiome, reduction of inflammation, upregulation of antioxidant enzymes, and attenuation of tumor growth. Understanding of such mechanisms might propose further clinical applications for metformin.

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