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.

scholarly journals Hepatic Glucose Output Inhibition by Mexican Plants Used in the Treatment of Type 2 Diabetes

2020 ◽  
Vol 11 ◽  
Author(s):  
Gerardo Mata-Torres ◽  
Adolfo Andrade-Cetto ◽  
Fernanda Artemisa Espinoza-Hernández ◽  
René Cárdenas-Vázquez
Keyword(s):  
Type 2 Diabetes ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output

scholarly journals Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History

2021 ◽  
Vol 22 (5) ◽  
pp. 2596
Author(s):  
Hideaki Kaneto ◽  
Tomohiko Kimura ◽  
Atsushi Obata ◽  
Masashi Shimoda ◽  
Kohei Kaku
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Transporter ◽  
Adenosine Monophosphate ◽  
Mechanisms Of Action ◽  
Neoplastic Cells ◽  
Insulin Sensitizer ◽  
First Choice

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.

scholarly journals Effects of 7 days of exercise training on insulin sensitivity and responsiveness in type 2 diabetes mellitus

2009 ◽  
Vol 297 (1) ◽  
pp. E151-E156 ◽  
Author(s):  
John P. Kirwan ◽  
Thomas P. J. Solomon ◽  
Daniel M. Wojta ◽  
Myrlene A. Staten ◽  
John O. Holloszy
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Short Term ◽  
Hepatic Glucose

The objectives of this study were to determine whether 1) the improvement in insulin action induced by short-term exercise training in patients with type 2 diabetes is due to an improvement in insulin sensitivity, an improvement in insulin responsiveness, or a combination of improved insulin sensitivity and responsiveness and 2) short-term exercise training results in improved suppression of hepatic glucose production by insulin. Fourteen obese patients with type 2 diabetes, age 64 ± 2 yr, underwent a two-stage hyperinsulinemic euglycemic clamp procedure, first stage 40 mU·m−2·min−1 insulin infusion, second stage 1,000 mU·m−2·min−1 insulin infusion, together with a [3-3H]glucose infusion, before and after 7 days of exercise. The training consisted of 30 min of cycling and 30 min of treadmill walking at ∼70% of maximal aerobic capacity daily for 7 days. The exercise program resulted in improvements in insulin action in the absence of weight loss. Glucose disposal rates during the euglycemic clamp were significantly increased at both hyperinsulinemic stages after training (40 mU: 1.84 ± 0.32 to 2.67 ± 0.37 mg·kg−1·min−1, P < 0.0001; 1,000 mU: 7.57 ± 0.61 to 8.84 ± 0.56 mg·kg−1·min−1, P = 0.008). Hepatic glucose production, both in the basal state (3.17 ± 0.43 vs. 2.54 ± 0.26 mg·kg−1·min−1, P = 0.05) and during the 40-mU clamp stage (1.15 ± 0.41 vs. 0.46 ± 0.20 mg·kg−1·min−1, P = 0.03), was significantly reduced after training. One week of vigorous exercise training can induce significant improvements in insulin action in type 2 diabetes. These improvements include increased peripheral insulin sensitivity and responsiveness as well as enhanced suppression of hepatic glucose production.

scholarly journals The Relationship between Type 2 Diabetes Mellitus and Related Thyroid Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Chaoxun Wang
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Thyroid Dysfunction ◽  
Enhanced Absorption ◽  
Hepatic Glucose ◽  
Glucose Output

Type 2 diabetes mellitus (T2DM) has an intersecting underlying pathology with thyroid dysfunction. The literature is punctuated with evidence indicating a contribution of abnormalities of thyroid hormones to type 2 DM. The most probable mechanism leading to T2DM in thyroid dysfunction could be attributed to perturbed genetic expression of a constellation of genes along with physiological aberrations leading to impaired glucose utilization and disposal in muscles, overproduction of hepatic glucose output, and enhanced absorption of splanchnic glucose. These factors contribute to insulin resistance. Insulin resistance is also associated with thyroid dysfunction. Hyper- and hypothyroidism have been associated with insulin resistance which has been reported to be the major cause of impaired glucose metabolism in T2DM. The state-of-art evidence suggests a pivotal role of insulin resistance in underlining the relation between T2DM and thyroid dysfunction. A plethora of preclinical, molecular, and clinical studies have evidenced an undeniable role of thyroid malfunctioning as a comorbid disorder of T2DM. It has been investigated that specifically designed thyroid hormone analogues can be looked upon as the potential therapeutic strategies to alleviate diabetes, obesity, and atherosclerosis. These molecules are in final stages of preclinical and clinical evaluation and may pave the way to unveil a distinct class of drugs to treat metabolic disorders.

312-OR: Gender-Specific Effects on Hepatic Fat Metabolism in Type 2 Diabetes before and after Remission

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 312-OR
Author(s):  
AHMAD AL-MRABEH ◽  
SHADEN MELHEM ◽  
SVIATLANA V. ZHYZHNEUSKAYA ◽  
CARL PETERS ◽  
ALISON C. BARNES ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fat Metabolism ◽  
Specific Effects ◽  
Before And After ◽  
Hepatic Fat ◽  
Gender Specific
Sign in / Sign up

Export Citation Format

Share Document