Home > News > Industry news
The principle of Metformin in reducing Blood glucose
Metformin was first found in 20 th century goat beans because of its high levels of guanidine. At that time, mainly used as a traditional treatment of diabetes plant drugs. Since its first use in the treatment of T2DM in 1957, it has been a long-term clinical practice. Because of its good effect of lowering glucose and its characteristics of weight loss and other cardiovascular risk factors, it has become a first-line drug for the treatment of T2DM recommended by many diabetic guidelines. And has been widely used in the world.
Metformin is familiar to diabetics. It is a basic drug for oral hypoglycemic drugs. Mild inhibition of mitochondrial respiratory chain complex Ⅰ and activation of adenylate activated protein kinase (AMPK) were used to reduce hepatic glucose output. At present, experts at home and abroad unanimously recommend metformin as the first choice of T2DM drug and hypoglycemic drug combined treatment of the basic drug.
Mechanism of Metformin lowering glucose(Huibai reagent: http://www.hnhbsj.com)
(1) hypoglycemia was mediated by adenylate activated protein kinase (AMPK). AMPK is an heteropolymer composed of catalytic subunit α and regulatory subunit β, γ, which is an energy receptor of cells and plays a protective role in cell function when energy is limited. When the ratio of adenosine triphosphate / adenosine monophosphate (AMP/ATP) is increased due to the imbalance in the production and consumption of adenosine triphosphate (ATP) in cells, AMPK can be activated by upstream kinases such as LKB1/STK11 and Ca2 / calmodulin kinase β (CaMKK β). Studies have shown that adenosine diphosphate (ADP) or ADP/ATP The ratio change could also bind to γ subunit, and then regulate the activation of AMPK.AMPKK to inhibit cell synthesis, promote catabolism, close the signal pathway that consumes ATP, and restore the energy balance of cells. The breakthrough in the study of metformin molecular mechanism is that in the early 21st century, two independent research groups reported that metformin could inhibit mitochondrial respiratory chain complex Ⅰ in a mild and specific manner. The reverse electron flow of respiratory chain complex I was selectively blocked and the production of mitochondrial reactive oxygen species (ROS) was inhibited. Metformin inhibits mitochondrial respiratory chain complex Ⅰ through mild, specific inhibition, leading to intracellular hyperactivity. Sexual energy reserves are reduced, activating AMPK, to inhibit liver sugar output, Hypoglycemia. The possible mechanism of AMPK mediated metformin to reduce liver glucose output is that (1) through the LKB1/AMPK signaling pathway, the factor binding protein 2 (CRTC2) of adenosine monophosphate (c-Amp) response is reduced, and the gene expression related to glycosylation is inhibited. Decreased hepatic glucose output; 2AMPK could increase the activity of liver deacetylase SirtuinSIRT1 (SirtuinSIRT1) and down-regulate CRTC2, thereby inhibiting the transcription of downstream glycosylated allogenes; 3AMPK could activate the orphan nuclear receptor (SHP) or inhibit kr. Pple like factor 15 (KLF15) decreased the expression level of glycosylated allogeneic genes. Therefore, metformin reduces liver glucose heterogenesis and inhibits hepatic glucose output in many ways. (2) reducing blood glucose by intestinal insulin. It was observed that metformin increased the level of glucagon like peptide-1 (GLP-1) without glucose intake in mice, but did not affect the (GIP) level of other intestinal peptides, such as tyrosine (YY),. Metformin has not been proved to affect the activity of dipeptidyl peptidase-4 (DPP-4). In addition, metformin can be mediated by PPAR- α. The gene expression of GLP-1 receptor in islet cells was increased by independent of AMPK pathway.
Adverse effects of metformin(Huibai reagent: http://www.hnhbsj.com)
1. Lactic acidosis: metformin lactic acidosis, although rare, has become one of the most concerned adverse reactions among clinicians due to its fatal consequences. At present, large clinical trials and meta-analysis at home and abroad have shown that there is no evidence that metformin may increase the risk of lactic acidosis. Most of the reported lactic acidosis cases did not meet the clinical diagnostic criteria of metformin associated lactic acidosis, and most of them were caused by the lack of strict control of contraindications and lack of dose adjustment of metformin.
2. Nephrotoxicity: metformin itself does not have nephrotoxicity, but it is generally thought that the drug should be excreted by the kidney in prototype. If the renal function of the patient is impaired, the drug may accumulate in the body, which may increase the risk of lactic acidosis. Therefore, most guidelines recommend careful use of drugs in patients with impaired renal function.
The material comes from the network.
For more information on biochemical reagents, check out Huibai Reagent's official website: http://www.hnhbsj.com
(all contents of this website are marked as "Huibai Reagent", copyright is owned by Huibai Reagent. Any media, website or individual shall not be reproduced without authorization, otherwise, legal liability will be investigated. Authorization to reprint should be marked "source: Huibai Reagent". This website indicates the source is other media content is reprinted, reprint only for the viewpoint sharing, the copyright belongs to the original author all, if has the infringement copyright, please contact us in time.
Metformin is familiar to diabetics. It is a basic drug for oral hypoglycemic drugs. Mild inhibition of mitochondrial respiratory chain complex Ⅰ and activation of adenylate activated protein kinase (AMPK) were used to reduce hepatic glucose output. At present, experts at home and abroad unanimously recommend metformin as the first choice of T2DM drug and hypoglycemic drug combined treatment of the basic drug.
Mechanism of Metformin lowering glucose(Huibai reagent: http://www.hnhbsj.com)
(1) hypoglycemia was mediated by adenylate activated protein kinase (AMPK). AMPK is an heteropolymer composed of catalytic subunit α and regulatory subunit β, γ, which is an energy receptor of cells and plays a protective role in cell function when energy is limited. When the ratio of adenosine triphosphate / adenosine monophosphate (AMP/ATP) is increased due to the imbalance in the production and consumption of adenosine triphosphate (ATP) in cells, AMPK can be activated by upstream kinases such as LKB1/STK11 and Ca2 / calmodulin kinase β (CaMKK β). Studies have shown that adenosine diphosphate (ADP) or ADP/ATP The ratio change could also bind to γ subunit, and then regulate the activation of AMPK.AMPKK to inhibit cell synthesis, promote catabolism, close the signal pathway that consumes ATP, and restore the energy balance of cells. The breakthrough in the study of metformin molecular mechanism is that in the early 21st century, two independent research groups reported that metformin could inhibit mitochondrial respiratory chain complex Ⅰ in a mild and specific manner. The reverse electron flow of respiratory chain complex I was selectively blocked and the production of mitochondrial reactive oxygen species (ROS) was inhibited. Metformin inhibits mitochondrial respiratory chain complex Ⅰ through mild, specific inhibition, leading to intracellular hyperactivity. Sexual energy reserves are reduced, activating AMPK, to inhibit liver sugar output, Hypoglycemia. The possible mechanism of AMPK mediated metformin to reduce liver glucose output is that (1) through the LKB1/AMPK signaling pathway, the factor binding protein 2 (CRTC2) of adenosine monophosphate (c-Amp) response is reduced, and the gene expression related to glycosylation is inhibited. Decreased hepatic glucose output; 2AMPK could increase the activity of liver deacetylase SirtuinSIRT1 (SirtuinSIRT1) and down-regulate CRTC2, thereby inhibiting the transcription of downstream glycosylated allogenes; 3AMPK could activate the orphan nuclear receptor (SHP) or inhibit kr. Pple like factor 15 (KLF15) decreased the expression level of glycosylated allogeneic genes. Therefore, metformin reduces liver glucose heterogenesis and inhibits hepatic glucose output in many ways. (2) reducing blood glucose by intestinal insulin. It was observed that metformin increased the level of glucagon like peptide-1 (GLP-1) without glucose intake in mice, but did not affect the (GIP) level of other intestinal peptides, such as tyrosine (YY),. Metformin has not been proved to affect the activity of dipeptidyl peptidase-4 (DPP-4). In addition, metformin can be mediated by PPAR- α. The gene expression of GLP-1 receptor in islet cells was increased by independent of AMPK pathway.
Adverse effects of metformin(Huibai reagent: http://www.hnhbsj.com)
1. Lactic acidosis: metformin lactic acidosis, although rare, has become one of the most concerned adverse reactions among clinicians due to its fatal consequences. At present, large clinical trials and meta-analysis at home and abroad have shown that there is no evidence that metformin may increase the risk of lactic acidosis. Most of the reported lactic acidosis cases did not meet the clinical diagnostic criteria of metformin associated lactic acidosis, and most of them were caused by the lack of strict control of contraindications and lack of dose adjustment of metformin.
2. Nephrotoxicity: metformin itself does not have nephrotoxicity, but it is generally thought that the drug should be excreted by the kidney in prototype. If the renal function of the patient is impaired, the drug may accumulate in the body, which may increase the risk of lactic acidosis. Therefore, most guidelines recommend careful use of drugs in patients with impaired renal function.
The material comes from the network.
For more information on biochemical reagents, check out Huibai Reagent's official website: http://www.hnhbsj.com
(all contents of this website are marked as "Huibai Reagent", copyright is owned by Huibai Reagent. Any media, website or individual shall not be reproduced without authorization, otherwise, legal liability will be investigated. Authorization to reprint should be marked "source: Huibai Reagent". This website indicates the source is other media content is reprinted, reprint only for the viewpoint sharing, the copyright belongs to the original author all, if has the infringement copyright, please contact us in time.
Room 1103, Building C3, Nol 27 Wenxuan Road, Yuelu District, Changsha City, Hunan, China.
86-731-85525705
86-13319518603
hnybbio@163.com
QQ customer service
