If you’re looking for Metformin Uses, you’ve come to the right place. Metformin is, a widely used diabetes drug that may offer potential benefits beyond treating diabetes. These include: inhibiting the NF-kB pathway and inhibiting cancer cell proliferation. It can also increase the sensitivity of muscle cells to insulin.
Reduces proliferation of cancer cells
Metformin has shown to reduce the proliferation of cancer cells in several animal models, including mice. Its effect on tumorigenesis has been studied in various cancer types, including pancreatic cancer. In vitro experiments showed that metformin inhibits the growth of tumor cells by reducing levels of LKB1 and mTORC1. In cancer cells, metformin inhibits the mTORC1 signaling pathway, inhibiting cell proliferation and protein synthesis.
Inhibition of the mTOR pathway by metformin proceeds in a dependent manner and involves AMPK activation. AMPK phosphorylates the tuberous sclerosis complex protein 2, which inhibits mTORC1. These effects result in decreased protein synthesis and cell growth. Early studies examining metformin’s anti-cancer effects focused on breast cancer cells. In addition, Dowling and colleagues reported that metformin inhibited translation of breast cancer cells. Meanwhile, Mohammed and colleagues reported that metformin reduced the growth of pancreatic cancer in transgenic mice.
In addition to reducing the proliferation of cancer cells, metformin also has other benefits. Metformin inhibits the expression of CSC-specific genes, and it inhibits the growth of gastrointestinal and prostate cancer cells. Moreover, metformin inhibits cancer cells by affecting the chloride intracellular channel-1, and AMPK signaling pathways.
Metformin inhibits AMPK, the protein that controls cell proliferation and cell division. It also inhibits the expression of mTOR, a protein involved in the growth metabolism of tumor cells. This inhibitory effect is largely dependent on the type of tumor cell. This may be due to the effect on the cell-cycle.
Metformin also inhibits PI3K/Akt/mTOR signaling pathways. These enzymes are important in cellular growth and metabolism. Metformin inhibits the activity of these enzymes by inhibiting the production of ATP and phosphoinositide 3-kinase. In addition, it inhibits the mTOR-dependent activity of AMPK. This inhibitory effect is, associated with metformin’s antitumor effect in breast cancer cells.
Increases sensitivity of muscle cells to insulin
Metformin is an oral medication, used to treat diabetes, and has shown promise in improving the sensitivity of muscle cells to insulin. Metformin has several effects on the insulin signalling pathway, including the activation of PI 3-kinase and tyrosine phosphorylation of the insulin receptor. These effects may suggest the drug’s potential as a novel therapeutic target.
Metformin enhances glucose uptake in L6 cells and reverses insulin signaling defects in rat adipocytes. It also inhibits insulin signaling in skeletal muscle and liver cells. However, the exact mechanism of metformin’s action is unclear.
Metformin improves insulin sensitivity by increasing the basal level of p38. In addition, it improves the tyrosine phosphorylation of IR-b in insulin-resistant myotubes. Metformin’s effect on muscle cells is, mediated via an indirect effect on cellular oxidative stress.
Metformin enhances glucose uptake by inhibiting SHIP2. Similarly, metformin inhibits SHIP2 activity in kidney and skeletal muscle cells. This mechanism helps improve insulin sensitivity and promote glucose uptake in peripheral tissues. However, further study is needed to understand the precise mechanism of how metformin works.
Metformin also improves glucose uptake by inhibiting the p38 MAPK pathway. It also blocks the activity of glucagon-like peptide-1 and N-methyl-D-aspartate receptors in skeletal muscle cells. This finding also suggests that metformin can decrease blood glucose levels by increasing the sensitivity of muscle cells to insulin.
In animal studies, metformin increases muscle cell sensitivity to insulin. The drug stimulates the expression of GLUT234 and SGLT1. In humans, metformin increases the expression of GLUT2. The drug also increases the activity of SGLT1 and GLUT234 receptors in the liver.
Inhibits NF-kB
Metformin inhibits the NF-kB pathway, which is, implicated in the development of many diseases, including cardiovascular disease. This pathway is more active as we age and is the main driver of chronic systemic inflammation. Metformin is unique in its ability to inhibit NF-kB, and may be a promising new treatment for heart failure patients.
Metformin inhibits the nuclear translocation of NF-kB, and reduces the expression of several downstream molecules. In vivo, metformin inhibits NF-kB activity in macrophages by blocking its nuclear translocation and inhibiting the expression of various pro-inflammatory cytokines, including iNOS and Cox2. In addition, metformin inhibits NF-kB expression in smooth muscle cells and the production of inflammatory cytokines.
To study the mechanism of metformin’s inhibitory effect on NF-kB, the authors studied apoE expression in macrophages. They found that NF-kB binds to the distal regulatory element of the apoE gene. Metformin inhibits NF-kb nuclear translocation, and it improves apoE levels in macrophages under inflammatory stress.
In addition, metformin inhibits p65 acetylation, a signal that activates the NF-kB pathway in cells. In mice, NF-kB inhibition inhibits this pathway. This effect was measured by measuring heart rate variability (HRV) and NF-kB binding activity. This effect has been found to increase the median life span by 20% in these animals.
Interestingly, metformin inhibits tumor development and suppresses tumor growth in laboratory mice. However, its mechanism of action is not fully understood. In one study, metformin treated mice showed increased expression of M1-related cytokines while suppressing M2-related cytokines. In addition, metformin inhibited the secretion of cytokines from M2 macrophages.
Stimulates ovulation in premenopausal women
A recent study has revealed that metformin can stimulate ovulation in premenopaual women. Compared to placebo, metformin stimulated ovulation in more than two-thirds of treated women. However, the study’s findings are not conclusive. Moreover, metformin may interfere with the body’s normal ovulation process.
To assess whether metformin stimulates ovulation in women, researchers performed an ovulation induction trial on obese women with PCOS. The participants were, randomly assigned to receive either metformin 500 mg three times daily or a placebo for 34 days. Women were also given CC 50 mg for five days. The study determined that ovulation occurred when serum P was greater than 8 ng/ml.
In women with PCOS, high insulin and androgen levels may prevent ovulation. During the menstrual cycle, ovulation occurs once a month when a follicle in the ovary develops an ovum. The ovum then exits the ovary and travels through the fallopian tubes to the uterus where fertilization occurs.
One study, found that metformin stimulates ovulation in women with PCOS, although the results are, limited. Although metformin may not increase the chance of conceiving, a significant reduction in BMI was observed in women treated with the drug. This study also showed that metformin can be combined with clomiphene citrate to induce ovulation. However, the results of this trial are limited and need to be confirmed in randomized prospective studies.
