INSR and Its Potential as A Drug Target (G3643)

Target Name: INSR

NCBI ID: G3643

INSR

INSR and Its Potential as A Drug Target

The insulin receptor (IR) is a transmembrane protein that plays a crucial role in the regulation of glucose metabolism. It is a key target for many diseases, including diabetes, obesity, and cancer. The INSR gene has four splice variants, INSR1, INSR2, INSR3, and INSR4, which result in different insulin receptor levels and functions. INSR has also been implicated in the development and progression of many diseases, including cancer. Therefore, it is a promising drug target for the development of new treatments.

Diseases associated with INSR

INSR is involved in the regulation of several diseases, including diabetes, obesity, cancer, and neurodegenerative diseases. It is a key target for many diseases because of its central role in the regulation of glucose metabolism.

Diabetes is a chronic metabolic disorder that is characterized by high blood sugar levels. INSR plays a crucial role in the regulation of glucose metabolism, as it is the primary target for the hormone insulin. Insulin is a protein produced by the pancreas that helps to lower blood sugar levels. INSR helps to regulate the amount of insulin produced by the pancreas to match the levels of glucose in the blood. If INSR is not functioning correctly, it can lead to an increase in blood sugar levels, which can lead to a variety of negative health consequences, including the development of diabetes.

Obesity is a serious public health issue that is characterized by excess body weight. INSR is involved in the regulation of body weight because it is the primary target for the hormone leptin. Leptin is a protein produced by the body that helps to regulate body weight. INSR helps to regulate the amount of leptin produced by the body to match the levels of food intake. If INSR is not functioning correctly, it can lead to an increase in body weight, which can lead to a variety of negative health consequences, including the development of obesity.

In addition to diabetes and obesity, INSR is also involved in the regulation of cancer development. INSR has been shown to play a role in the development and progression of many cancers, including breast, ovarian, and prostate cancers. INSR has also been shown to promote the growth and survival of cancer cells. Therefore, targeting INSR has been shown to be an effective way to treat cancer.

Neurodegenerative diseases are a group of diseases that are characterized by the progressive loss of brain cells. INSR is involved in the regulation of neurodegenerative diseases because it is the primary target for the hormone neurotrophin. Neurotrophin is a protein produced by the body that helps to regulate the growth and survival of brain cells. INSR helps to regulate the amount of neurotrophin produced by the body to match the levels of brain cell loss. If INSR is not functioning correctly, it can lead to a progressive loss of brain cells, which can lead to the development of neurodegenerative diseases.

Drugs that target INSR

INSR is a drug target that has the potential to be used to treat a variety of diseases. Some drugs that target INSR include:

1. GLP-1 receptor agonists: GLP-1 receptor agonists are a type of drug that is used to treat type 2 diabetes. They work by stimulating the release of insulin from the pancreas and suppressing the release of glucagon from the pancreas. GLP-1 receptor agonists have been shown to be effective in reducing blood sugar levels and improving lipid profiles in people with type 2 diabetes.

2. SGLT2 inhibitors: SGLT2 inhibitors are a type of drug that is used to treat type 2 diabetes. They work by inhibiting the action of sodium-glucose cotransporter 2 (SGLT2), which is a protein that helps to regulate the reabsorption of glucose from the kidneys. SGLT2 inhibitors have been shown to be effective in reducing blood sugar levels and improving lipid profiles in people with type 2 diabetes.

3.

Protein Name: Insulin Receptor

Functions: Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity)

The "INSR Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about INSR comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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