Browse result page of ThPDB2
This is the result page of the browse module of ThPDB2. This page gives the information about the query submitted by the user as per the browse category. Further details of the entries can be seen by clicking on the ID or THPP_ID. Further the user can sort the entries on the basis of various fields by clicking on the respective headers. The user can also download the results in various formats.
Tabular representation:
| ID | THPP_ID | Therapeutic Name | Sequence | Molecular Weight | Chemical Formula | Isoelectric Point | Hydrophobicity | Melting Point | Half Life | Description | Disease/Indication | Pharmacodynamics | Mechanism of Action | Toxicity | Metabolism | Absorption | Volume of Distribution | Clearance | Categories | Patent Number | Date of Issue | Date of Expiry | Drug Interaction | Target | Brand Name | Company | Brand Description | Prescribed for | Chemical Name | Formulation | Physical Appearance | Route of Administation | Recommended Dosage | Contraindication | Side Effects | Useful Links 1 | Useful Links 2 | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 10022 | Th1003 | Dornase alfa | >Th1003_Dornase_alfa LKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQEVRDSHLTAVGKLLDNLNQDAPDTYHYVVSEPLGRNSYKERYLFVYRPDQVSAVDSYYYDDGCEPCGNDTFNREPAIVRFFSRFTEVREFAIVPLHAAPGDAVAEIDALYDVYLDVQEKWGLEDVMLMGDFNAGCSYVRPSQWSSIRLWTSPTFQWLIPDSADTTATPTHCAYDRIVVAGMLLRGAVVPDSALPFNFQAAYGLSDQLAQAISDHYPVEVMLK | 29253.9 | C1321H1999N339O396S9 | 4.58 | -0.083 | 67 | NA | It is a biosynthetic form of human enzyme DNase I, produced in genetically modified CHO cells using recombinant DNA technology. The 260 amino acid synthetic sequence of dornase alfa is identical to the endogenous human enzyme. Dornase alfa cleaves extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products(without affecting intracellular DNA). In individuals with cystic fibrosis, extracellular DNA, an extremely viscous anion, is released by degenerating leukocytes which accumulate during inflammatory responses to infections. Enzymatic breakdown of this extracellular DNA causes reduction in sputum viscosity and viscoelasticity. | Used in the treatment of cystic fibrosis as adjunct therapy. | Cystic fibrosis (CF) is characterized by retention of viscous purulent secretions in the airways. These thick secretions contribute to reduced pulmonary function and to frequent pulmonary infection. Purulent pulmonary secretions of individuals with cystic fibrosis contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to these infections. Dornase alfa hydrolyzes the DNA in sputum of CF patients and reduces sputum viscosity and viscoelasticity. The enzyme does not appear to affect sputum in the absence of an inflammatory response to infection, nor does it affect the sputum of healthy individuals. | Dornase alfa is a biosynthetic form of human DNase I. The enzyme is involved in endonucleolytic cleavage of extracellular DNA to 5´-phosphodinucleotide and 5´-phospho-oligonucleotide end products. It has no effect on intracellular DNA. Optimal activity dependent on the presence of divalent cations such as calcium and magnesium. Extracellular DNA is a viscous anionic polymer and its breakdown appears to improve the viscosity and viscoelasticity of purulent sputum of individuals with CF. | Adverse reactions occur at a rate of 1/1000 and are usually mild and transient in nature. Reported adverse effects include decreased lung function, rash, urticaria, chest pain (pleuritic/non-cardiac), dyspepsia, voice alteration (hoarseness), pharyngitis | NA | Systemic absorption is undetectable when administered via inhalation. | NA | NA | Amino Acids, Peptides, and Proteins, Cough and Cold Preparations, Decreased Respiratory Secretion Viscosity, Deoxyribonucleases, Endodeoxyribonucleases, Endonucleases, Enzymes, Enzymes and Coenzymes, Esterases, Expectorants, Hydrolases, Proteins, Recombinant Human Deoxyribonuclease 1 | CA2184581 | 22-Feb-2005 | 28-Feb-2015 | Afrezza (insulin inhalation, rapid acting) | DNA | Pulmozyme | Genentech Inc | Genentech Inc | Pulmozyme is used to improve lung function by thinning pulmonary secretions and reducing the risk of respiratory tract infections in people with cystic fibrosis. | NA | The aqueous formulation contains 1.0 mg/mL dornase alfa, 0.15 mg/mL calcium chloride dihydrate and 8.77 mg/mL sodium chloride. The solution contains no preservative and supports a pH of 6.3. | NA | Administered by inhalation of an aerosol mist prod | NA | allergic | Serious side effects include difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives; increased difficulty breathing; chest pain; or fever. Less serious side effects may be voice alteration; sore throat; rash. | Link | NA | NA |
| 11255 | Th1244 | Insulin human | >Th1244_Insulin_human GIVEQCCTSICSLYQLENYCN | 5808 | C257H383N65O77S6 | NA | NA | 81 °C | Systemic insulin disposition (apparent terminal half-life) following oral inhalation of 4 to 48 units of human insulin was 120-206 minutes. | Human Insulin, also known as Regular Insulin, is a short-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Human insulin is produced by recombinant DNA technology and is identical to endogenously produced insulin. Typically prescribed for the management of diabetes mellitus, insulin is a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions. Insulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after trying several oral medications such as [DB00331], [DB01120], or [DB01261] have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. Marketed as the brand name product Humulin R or Novolin R, human insulin begins to exert its effects within 30 minutes of subcutaneous administration, while peak levels occur 3-4 hours after administration. Due to its quick onset of action, human insulin is considered "bolus insulin" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting "basal insulin" such as [DB01307], [DB09564], and [DB00047] to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia. Human insulin is also available in an inhalable form, intended to be used as a bolus meal-time insulin. Exubera was the first inhaled insulin available on the market and was developed by Inhale Therapeutics (later named Nektar Therapeutics). Unfortunately, limited uptake by physicians and patients, poor sales, bulky packaging, and concerns over the possible impact on lung cancer development resulted in Exubera products being withdrawn from the US markets [A176005]. Exubera was followed by Afrezza, a monomeric inhaled insulin developed by Mannkind Corporation, which received FDA approval in 2016. While still available in the US, Afrezza has had similar concerns associated with its use, and had an FDA "black box" warning added to it to warn about use in patients with chronic lung disease. Afrezza does not currently have Health Canada or European Medicines Agency approval for marketing in Canada or the EU. Human Insulin is a 51 residue peptide hormone produced by recombinant DNA technology by inserting the human insulin gene into Escherichia coli bacteria or Saccharomyces cerevisiae. The structure is identical to native human insulin, with two amino acid chains covalently linked by disulfide bonds. Human insulin is also available in an intermediate-acting form as NPH (Neutral Protamine Hagedorn) as the marketed products Novolin N and Humulin N. NPH insulin is provided as a crystalline suspension of insulin with protamine and zinc, resulting in an onset of action in 1 to 3 hours, duration of action up to 24 hours, and peak action from 6 to 8 hours. Due to the added crystals, NPH insulin is typically cloudy when compared to other forms of insulin and has a neutral pH. Without an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy. | Human insulin is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). | The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism. | NA | The metabolism and elimination of orally inhaled human insulin are comparable to regular human insulin. | When injected subcutaneously, the glucose-lowering effect of human insulin begins approximately 30 minutes post-dose. After a single subcutaneous administration of 0.1 unit/kg of human insulin to healthy subjects, peak insulin concentrations occurred between 1.5 to 2.5 hours post-dose. When administered in an inhaled form (as the product Afrezza), the time to maximum serum insulin concentration ranges from 10-20 minutes after oral inhalation of 4 to 48 units of human insulin. Serum insulin concentrations declined to baseline by approximately 60-240 minutes for these dose levels. Intrapatient variability in insulin exposure measured by AUC and Cmax is approximately 16% (95% CI 12-23%) and 21% (95% CI 16-30%), respectively. | NA | NA | NA | 9192675 | 24-11-2015 | 12-06-2029 | NA | Insulin receptor,Insulin-like growth factor 1 receptor,Carboxypeptidase E,Protein NOV homolog,Low-density lipoprotein receptor-related protein 2,Insulin-like growth factor-binding protein 7 | Exubera | Pfizer Inc. | Pfizer Inc. | Respiratory (inhalation) | 1 mg/1 | EXUBERA (insulin human [rdna origin]) is contraindicated in patients hypersensitive to EXUBERA (insulin human [rdna origin]) or one of its excipients. EXUBERA (insulin human [rdna origin]) is contraindicated in patients who smoke or who have discontinued smoking less than 6 months prior to starting EXUBERA (insulin human [rdna origin]) therapy. If a patient starts or resumes smoking, EXUBERA (insulin human [rdna origin]) must be discontinued immediately due to the increased risk of hypoglycemia, and an alternative treatment must be utilized (see CLINICAL PHARMACOLOGY, Special Populations, Smoking). The safety and efficacy of EXUBERA (insulin human [rdna origin]) in patients who smoke have not been established. EXUBERA (insulin human [rdna origin]) is contraindicated in patients with unstable or poorly controlled lung disease, because of wide variations in lung function that could affect the absorption of EXUBERA (insulin human [rdna origin]) and increase the risk of hypoglycemia or hyperglycemia. | cough, sore throat, runny or stuffy nose, dry mouth, ear pain, respiratory tract infection, shortness of breath, bronchitis, asthma, nosebleed, laryngitis, pneumonia, or changes in voice. | Insulin inhalation was withdrawn from the U.S. market in 2007 due to lack of consumer demand for the product. No drug safety concerns were cited in this withdrawal. Exubera is a rapid-acting form of human insulin that is inhaled through the mouth. It works by lowering levels of glucose (sugar) in the... | EXUBERA (insulin human [rdna origin]) is indicated for the treatment of adult patients with diabetes mellitus for the control of hyperglycemia. EXUBERA (insulin human [rdna origin]) has an onset of action similar to rapid-acting insulin analogs and has a duration of glucose-lowering activity comparable to subcutaneously administered regular human insulin. In patients with type 1 diabetes, EXUBERA (insulin human [rdna origin]) should be used in regimens that include a longer-acting insulin. In patients with type 2 diabetes, EXUBERA (insulin human [rdna origin]) can be used as monotherapy or in combination with oral agents or longer-acting insulins. | NA | NA | Link | Link | NA |
| 11256 | Th1244 | Insulin human | >Th1244_Insulin_human GIVEQCCTSICSLYQLENYCN | 5808 | C257H383N65O77S6 | NA | NA | 81 °C | Systemic insulin disposition (apparent terminal half-life) following oral inhalation of 4 to 48 units of human insulin was 120-206 minutes. | Human Insulin, also known as Regular Insulin, is a short-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Human insulin is produced by recombinant DNA technology and is identical to endogenously produced insulin. Typically prescribed for the management of diabetes mellitus, insulin is a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions. Insulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after trying several oral medications such as [DB00331], [DB01120], or [DB01261] have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. Marketed as the brand name product Humulin R or Novolin R, human insulin begins to exert its effects within 30 minutes of subcutaneous administration, while peak levels occur 3-4 hours after administration. Due to its quick onset of action, human insulin is considered "bolus insulin" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting "basal insulin" such as [DB01307], [DB09564], and [DB00047] to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia. Human insulin is also available in an inhalable form, intended to be used as a bolus meal-time insulin. Exubera was the first inhaled insulin available on the market and was developed by Inhale Therapeutics (later named Nektar Therapeutics). Unfortunately, limited uptake by physicians and patients, poor sales, bulky packaging, and concerns over the possible impact on lung cancer development resulted in Exubera products being withdrawn from the US markets [A176005]. Exubera was followed by Afrezza, a monomeric inhaled insulin developed by Mannkind Corporation, which received FDA approval in 2016. While still available in the US, Afrezza has had similar concerns associated with its use, and had an FDA "black box" warning added to it to warn about use in patients with chronic lung disease. Afrezza does not currently have Health Canada or European Medicines Agency approval for marketing in Canada or the EU. Human Insulin is a 51 residue peptide hormone produced by recombinant DNA technology by inserting the human insulin gene into Escherichia coli bacteria or Saccharomyces cerevisiae. The structure is identical to native human insulin, with two amino acid chains covalently linked by disulfide bonds. Human insulin is also available in an intermediate-acting form as NPH (Neutral Protamine Hagedorn) as the marketed products Novolin N and Humulin N. NPH insulin is provided as a crystalline suspension of insulin with protamine and zinc, resulting in an onset of action in 1 to 3 hours, duration of action up to 24 hours, and peak action from 6 to 8 hours. Due to the added crystals, NPH insulin is typically cloudy when compared to other forms of insulin and has a neutral pH. Without an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy. | Human insulin is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). | The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism. | NA | The metabolism and elimination of orally inhaled human insulin are comparable to regular human insulin. | When injected subcutaneously, the glucose-lowering effect of human insulin begins approximately 30 minutes post-dose. After a single subcutaneous administration of 0.1 unit/kg of human insulin to healthy subjects, peak insulin concentrations occurred between 1.5 to 2.5 hours post-dose. When administered in an inhaled form (as the product Afrezza), the time to maximum serum insulin concentration ranges from 10-20 minutes after oral inhalation of 4 to 48 units of human insulin. Serum insulin concentrations declined to baseline by approximately 60-240 minutes for these dose levels. Intrapatient variability in insulin exposure measured by AUC and Cmax is approximately 16% (95% CI 12-23%) and 21% (95% CI 16-30%), respectively. | NA | NA | NA | 8215300 | 10-07-2012 | 24-11-2022 | NA | Insulin receptor,Insulin-like growth factor 1 receptor,Carboxypeptidase E,Protein NOV homolog,Low-density lipoprotein receptor-related protein 2,Insulin-like growth factor-binding protein 7 | Exubera | Pfizer Inc. | Pfizer Inc. | Respiratory (inhalation) | 3 mg/1 | EXUBERA (insulin human [rdna origin]) is contraindicated in patients hypersensitive to EXUBERA (insulin human [rdna origin]) or one of its excipients. EXUBERA (insulin human [rdna origin]) is contraindicated in patients who smoke or who have discontinued smoking less than 6 months prior to starting EXUBERA (insulin human [rdna origin]) therapy. If a patient starts or resumes smoking, EXUBERA (insulin human [rdna origin]) must be discontinued immediately due to the increased risk of hypoglycemia, and an alternative treatment must be utilized (see CLINICAL PHARMACOLOGY, Special Populations, Smoking). The safety and efficacy of EXUBERA (insulin human [rdna origin]) in patients who smoke have not been established. EXUBERA (insulin human [rdna origin]) is contraindicated in patients with unstable or poorly controlled lung disease, because of wide variations in lung function that could affect the absorption of EXUBERA (insulin human [rdna origin]) and increase the risk of hypoglycemia or hyperglycemia. | cough, sore throat, runny or stuffy nose, dry mouth, ear pain, respiratory tract infection, shortness of breath, bronchitis, asthma, nosebleed, laryngitis, pneumonia, or changes in voice. | Insulin inhalation was withdrawn from the U.S. market in 2007 due to lack of consumer demand for the product. No drug safety concerns were cited in this withdrawal. Exubera is a rapid-acting form of human insulin that is inhaled through the mouth. It works by lowering levels of glucose (sugar) in the... | EXUBERA (insulin human [rdna origin]) is indicated for the treatment of adult patients with diabetes mellitus for the control of hyperglycemia. EXUBERA (insulin human [rdna origin]) has an onset of action similar to rapid-acting insulin analogs and has a duration of glucose-lowering activity comparable to subcutaneously administered regular human insulin. In patients with type 1 diabetes, EXUBERA (insulin human [rdna origin]) should be used in regimens that include a longer-acting insulin. In patients with type 2 diabetes, EXUBERA (insulin human [rdna origin]) can be used as monotherapy or in combination with oral agents or longer-acting insulins. | NA | NA | Link | Link | NA |
| 11257 | Th1244 | Insulin human | >Th1244_Insulin_human GIVEQCCTSICSLYQLENYCN | 5808 | C257H383N65O77S6 | NA | NA | 81 °C | Systemic insulin disposition (apparent terminal half-life) following oral inhalation of 4 to 48 units of human insulin was 120-206 minutes. | Human Insulin, also known as Regular Insulin, is a short-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Human insulin is produced by recombinant DNA technology and is identical to endogenously produced insulin. Typically prescribed for the management of diabetes mellitus, insulin is a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions. Insulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after trying several oral medications such as [DB00331], [DB01120], or [DB01261] have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own. Marketed as the brand name product Humulin R or Novolin R, human insulin begins to exert its effects within 30 minutes of subcutaneous administration, while peak levels occur 3-4 hours after administration. Due to its quick onset of action, human insulin is considered "bolus insulin" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting "basal insulin" such as [DB01307], [DB09564], and [DB00047] to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia. Human insulin is also available in an inhalable form, intended to be used as a bolus meal-time insulin. Exubera was the first inhaled insulin available on the market and was developed by Inhale Therapeutics (later named Nektar Therapeutics). Unfortunately, limited uptake by physicians and patients, poor sales, bulky packaging, and concerns over the possible impact on lung cancer development resulted in Exubera products being withdrawn from the US markets [A176005]. Exubera was followed by Afrezza, a monomeric inhaled insulin developed by Mannkind Corporation, which received FDA approval in 2016. While still available in the US, Afrezza has had similar concerns associated with its use, and had an FDA "black box" warning added to it to warn about use in patients with chronic lung disease. Afrezza does not currently have Health Canada or European Medicines Agency approval for marketing in Canada or the EU. Human Insulin is a 51 residue peptide hormone produced by recombinant DNA technology by inserting the human insulin gene into Escherichia coli bacteria or Saccharomyces cerevisiae. The structure is identical to native human insulin, with two amino acid chains covalently linked by disulfide bonds. Human insulin is also available in an intermediate-acting form as NPH (Neutral Protamine Hagedorn) as the marketed products Novolin N and Humulin N. NPH insulin is provided as a crystalline suspension of insulin with protamine and zinc, resulting in an onset of action in 1 to 3 hours, duration of action up to 24 hours, and peak action from 6 to 8 hours. Due to the added crystals, NPH insulin is typically cloudy when compared to other forms of insulin and has a neutral pH. Without an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy. | Human insulin is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus. | Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). | The primary activity of insulin is the regulation of glucose metabolism. Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor is able to autophosphorylate and phosphorylate numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. These activated proteins, in turn, lead to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC) which play a critical role in metabolism and catabolism. | NA | The metabolism and elimination of orally inhaled human insulin are comparable to regular human insulin. | When injected subcutaneously, the glucose-lowering effect of human insulin begins approximately 30 minutes post-dose. After a single subcutaneous administration of 0.1 unit/kg of human insulin to healthy subjects, peak insulin concentrations occurred between 1.5 to 2.5 hours post-dose. When administered in an inhaled form (as the product Afrezza), the time to maximum serum insulin concentration ranges from 10-20 minutes after oral inhalation of 4 to 48 units of human insulin. Serum insulin concentrations declined to baseline by approximately 60-240 minutes for these dose levels. Intrapatient variability in insulin exposure measured by AUC and Cmax is approximately 16% (95% CI 12-23%) and 21% (95% CI 16-30%), respectively. | NA | NA | NA | 8146588 | 03-04-2012 | 24-04-2023 | NA | Insulin receptor,Insulin-like growth factor 1 receptor,Carboxypeptidase E,Protein NOV homolog,Low-density lipoprotein receptor-related protein 2,Insulin-like growth factor-binding protein 7 | Exubera | Pfizer Inc. | Pfizer Inc. | Respiratory (inhalation) | NA | EXUBERA (insulin human [rdna origin]) is contraindicated in patients hypersensitive to EXUBERA (insulin human [rdna origin]) or one of its excipients. EXUBERA (insulin human [rdna origin]) is contraindicated in patients who smoke or who have discontinued smoking less than 6 months prior to starting EXUBERA (insulin human [rdna origin]) therapy. If a patient starts or resumes smoking, EXUBERA (insulin human [rdna origin]) must be discontinued immediately due to the increased risk of hypoglycemia, and an alternative treatment must be utilized (see CLINICAL PHARMACOLOGY, Special Populations, Smoking). The safety and efficacy of EXUBERA (insulin human [rdna origin]) in patients who smoke have not been established. EXUBERA (insulin human [rdna origin]) is contraindicated in patients with unstable or poorly controlled lung disease, because of wide variations in lung function that could affect the absorption of EXUBERA (insulin human [rdna origin]) and increase the risk of hypoglycemia or hyperglycemia. | cough, sore throat, runny or stuffy nose, dry mouth, ear pain, respiratory tract infection, shortness of breath, bronchitis, asthma, nosebleed, laryngitis, pneumonia, or changes in voice. | Insulin inhalation was withdrawn from the U.S. market in 2007 due to lack of consumer demand for the product. No drug safety concerns were cited in this withdrawal. Exubera is a rapid-acting form of human insulin that is inhaled through the mouth. It works by lowering levels of glucose (sugar) in the... | EXUBERA (insulin human [rdna origin]) is indicated for the treatment of adult patients with diabetes mellitus for the control of hyperglycemia. EXUBERA (insulin human [rdna origin]) has an onset of action similar to rapid-acting insulin analogs and has a duration of glucose-lowering activity comparable to subcutaneously administered regular human insulin. In patients with type 1 diabetes, EXUBERA (insulin human [rdna origin]) should be used in regimens that include a longer-acting insulin. In patients with type 2 diabetes, EXUBERA (insulin human [rdna origin]) can be used as monotherapy or in combination with oral agents or longer-acting insulins. | NA | NA | Link | Link | NA |