A review of evidence based hot spots of metformin in EASD2015

International Diabetes International Diabetes international 2015-10-27According to the fifty-first annual meeting of the European Associatio

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International Diabetes International Diabetes international 2015-10-27

According to the fifty-first annual meeting of the European Association for the study of diabetes (EASD) annual meeting from September 2015 to 18, held in Stockholm, Sweden, the capital of. Metformin as a first-line treatment for diabetes, the current EASD annual meeting announced a large number of metformin as the research object of the latest research results. This paper makes some important research points, the first time we learned on the progress of metformin syndrome.

A new perspective on the hypoglycemic mechanism of metformin partly dependent on GLP-1

Metformin is a first-line drug for the treatment of diabetes, and its main role is to inhibit glucose synthesis and gluconeogenesis. Studies have shown that metformin can increase the glucagon like peptide 1 (GLP-1) secretion, in this EASD conference, M. Hansen, the Danish study found that acute metformin can increase the secretion of GLP-1, reduce the postprandial blood glucose fluctuation, the hypoglycemic effect was partially dependent on GLP-1.

The control study was a double-blind, placebo, 12 cases of patients with type 2 diabetes were included in the results show that, compared with the placebo + saline, metformin + saline increased plasma GLP-1 incremental area under the curve (iAUC), and reduce postprandial blood glucose iAUC 58% (P< 0.05). When metformin combined with GLP-1 receptor antagonist exendin 9-39, compared with the saline + GLP-1 receptor antagonist exendin 9-39, only reduced postprandial blood glucose iAUC 25%. In addition, the ratio of C peptide / glucose was significantly higher after metformin + saline, however, the difference was not significant after injection of exendin 9-39. Therefore, the researchers believe that a large part of metformin hypoglycemic effect is GLP-1 dependent, which provides a new perspective to explore the mechanism of metformin hypoglycemic.

Study on the hypoglycemic mechanism of metformin

1 weight loss mechanism

Metformin increases the utilization of glucose and fatty acids in adipose tissue

In addition to lowering blood sugar, there is increasing evidence that metformin also affects lipid metabolism, weight loss and abdominal fat mass. However, its mechanism is still unclear.

Czech Republic's J. Trnovska et al. Found that metformin may enhance the utilization of brown adipose tissue (BAT) on sugars and fatty acids, may be involved in the process of metabolic syndrome, and improve related disorders.

The results showed that after 4 weeks of treatment with metformin mg/kg, the weight of male Wistar rats was significantly decreased, the weight of the visceral adipose tissue of the epididymis and kidney decreased, and the level of triglyceride decreased in the rats. In addition, metformin can reduce the accumulation of visceral adipose tissue in the liver, heart, aorta and diaphragm, increase the oxidation of palmitic acid in BAT, and increase the binding rate of palmitic acid to BAT. The combination rate of glucose and BAT was higher in metformin group, but it had no effect on basal and insulin stimulated glucose oxidation.

In addition, the study also found that metformin can reduce the level of plasma insulin, improve the level of high molecular weight adiponectin and reduce the plasma concentration of C reactive protein (CPR).

2 anti inflammatory mechanism

Metformin reduces TLR4 expression in monocytes of patients with type 2 diabetes mellitus

There are many cytokines involved in the pathogenesis of type 2 diabetes. A. et al., from Coppola, Italy, found that metformin was associated with downregulation of Toll like receptor 4 (TLR4) in monocytes from type 2 diabetes. TLR4 deficiency may lead to a reduction in the body's inflammatory response to leptin secretion, which may be used to explain the anti-inflammatory mechanism of metformin.

The study included 50 cases of Caucasian subjects, divided into 3 groups: 10 cases of healthy control group (HC), metformin treatment in patients with type 2 diabetes mellitus (MET-T2D), 20 cases of newly diagnosed and no drug therapy in patients with type 2 diabetes mellitus (Naï ve-T2D) in 20 cases. Whole blood (CBC) analysis showed that there was no difference in the number of monocytes in each group. Compared with HC group, Naï and ve-T2D increased in TLR2 group and TLR4 group. On the contrary, compared with the other two groups, the TLR4 of MET-T2D group decreased sharply, but the expression of TLR2 was not affected by metformin. Therefore, metformin may play an anti-inflammatory role by lowering TLR4.

3 potential mechanisms for the treatment of liver cirrhosis and liver cancer

Metformin attenuates hepatic fibrosis induced by hepatitis C virus

Many studies show that metformin can delay cancer progression and reduce cancer mortality, in patients with type 2 diabetes, metformin and hepatitis C virus (HCV) induced cirrhosis is related to the decrease of.

Study on the Korean J.H.Jeon found that metformin may reduce HCV induced activation of AMP activated protein kinase (AMPK) and orphan nuclear receptor SHP expression decreased, HCV infected cells to reverse fibrosis, at the same time, metformin can reduce the transforming growth factor beta (TGF- beta) gene expression and hepatic fibrosis in the. It can be seen that metformin can be used as a potential drug for the treatment of liver fibrosis, especially for patients with type 2 diabetes.

Metformin inhibits proliferation of hepatocellular carcinoma cells

Relationship between type 2 diabetes mellitus and hepatocellular carcinoma (HCC). A. Montesano et al. In vitro study of the molecular effects of metformin on human hepatocellular carcinoma cell line (HepG2) in Italy. The results showed that metformin could inhibit the proliferation of HepG2 by blocking the cell cycle in G0/G1 phase. Metformin is expected to become a new drug for the treatment of liver disease.

4 mechanisms for the treatment of pancreatic cancer

Metformin inhibits proliferation and migration of pancreatic stellate cells

Metformin can reduce the risk of pancreatic cancer in patients with type 2 diabetes and improve the prognosis of pancreatic cancer. Its role is through activation of AMPK in cancer cells and inhibition of mTOR signal to achieve. Activated pancreatic stellate cells are the key stromal cells involved in pancreatic fibrosis and pancreatic cancer progression. However, no study has been conducted to investigate the effects of metformin on pancreatic stellate cells.

In order to investigate the effect of metformin on pancreatic stellate cell protective effect, China from Zhongda Hospital Affiliated to Southeast University professor Li Ling metformin with different concentrations (2.5mmol/L, 5mmol/L and 10mmol/L) on primary mouse pancreatic stellate cells and immortalized mouse model of pancreatic stellate cells (imPSC) were cultured, cell proliferation was detected by MTT method. The scratch experiment evaluation of pancreatic stellate cell migration, and positive assessment of metformin two important regulatory molecules AMPK and mTOR play an important role in the effects of metformin on the proliferation and migration of pancreatic stellate cells in. It was found that metformin could inhibit the proliferation and migration of pancreatic stellate cells (P = 0.01) in a dose-dependent and time-dependent manner. Metformin can induce AMPK phosphorylation, the effect of 24 hours of peak; inhibition of Akt, mTOR and P70S6K phosphorylation (P are < 0.01), the effect of the peak of 48 hours. < p=" " >

These results suggest that metformin can inhibit the proliferation and migration of pancreatic stellate cells, activate the phosphorylation of AMPK, and inhibit the phosphorylation of Akt/mTOR/P70S6K. Further studies are needed to further investigate the possible molecular mechanisms of metformin on pancreatic stellate cells.

Summary

Since 1957, metformin has been used in the treatment of diabetes for more than half a century. Although metformin is a classic drug, but whether in clinical research or foundation, metformin Everfount to coruscate new vitality. The EASD annual meeting a lot of metformin released the latest research results make people mechanism of metformin hypoglycemic, weight loss, anti-inflammatory and possible treatment of liver cirrhosis, liver cancer and pancreatic cancer have further understanding, provides new evidence for the clinical application of metformin better.

(source: Editorial Department of International Diabetes)

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