User:Joanna Morelli/Sandbox 1
From Proteopedia
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== Manufacture == | == Manufacture == | ||
| - | Insulin glargine is made by recombinant DNA technology with ''Escherichia coli''. <ref name="one">McKeage, K., & Goa, K. L. (2001). Insulin glargine. Drugs, 61(11), 1599-1624.</ref> Insulin glargine was originally created by Aventis Pharmaceuticals and was accepted for use in 2000 in the USA and the EU. <ref name="two">Baeshen, N. A., Baeshen, M. N., Sheikh, A., Bora, R. S., Ahmed, M. M. M., Ramadan, H. A., ... & Redwan, E. M. (2014). Cell factories for insulin production. Microbial cell factories, 13(1), 141. | + | Insulin glargine is made by recombinant DNA technology with ''Escherichia coli''.<ref name="one">McKeage, K., & Goa, K. L. (2001). Insulin glargine. Drugs, 61(11), 1599-1624.</ref> Insulin glargine was originally created by Aventis Pharmaceuticals and was accepted for use in 2000 in the USA and the EU.<ref name="two">Baeshen, N. A., Baeshen, M. N., Sheikh, A., Bora, R. S., Ahmed, M. M. M., Ramadan, H. A., ... & Redwan, E. M. (2014). Cell factories for insulin production. Microbial cell factories, 13(1), 141. |
| - | </ref> Insulin glargine is created through the manipulation of amino acids. <ref name="two">Baeshen, N. A., Baeshen, M. N., Sheikh, A., Bora, R. S., Ahmed, M. M. M., Ramadan, H. A., ... & Redwan, E. M. (2014) Cell factories for insulin production. Microbial cell factories, 13(1), 141. | + | </ref> Insulin glargine is created through the manipulation of amino acids.<ref name="two">Baeshen, N. A., Baeshen, M. N., Sheikh, A., Bora, R. S., Ahmed, M. M. M., Ramadan, H. A., ... & Redwan, E. M. (2014) Cell factories for insulin production. Microbial cell factories, 13(1), 141. |
| - | </ref>. A glycine is added to the C-terminal A-chain asparagine and two arginines are added to the C-terminal B-chain threonine. <ref name="two">Baeshen, N. A., Baeshen, M. N., Sheikh, A., Bora, R. S., Ahmed, M. M. M., Ramadan, H. A., ... & Redwan, E. M. (2014). Cell factories for insulin production. Microbial cell factories, 13(1), 141. | + | </ref>. A glycine is added to the C-terminal A-chain asparagine and two arginines are added to the C-terminal B-chain threonine.<ref name="two">Baeshen, N. A., Baeshen, M. N., Sheikh, A., Bora, R. S., Ahmed, M. M. M., Ramadan, H. A., ... & Redwan, E. M. (2014). Cell factories for insulin production. Microbial cell factories, 13(1), 141. |
| - | </ref> The final drug product forms at a pH of 4 through the expression of ''E. coli'' and the generation of the precursor proinsulin. <ref name="three">Walsh, G. (2005). Therapeutic insulins and their large-scale manufacture. Applied microbiology and biotechnology, 67(2), 151-159. | + | </ref> The final drug product forms at a pH of 4 through the expression of ''E. coli'' and the generation of the precursor proinsulin.<ref name="three">Walsh, G. (2005). Therapeutic insulins and their large-scale manufacture. Applied microbiology and biotechnology, 67(2), 151-159. |
</ref> | </ref> | ||
== Structure == | == Structure == | ||
| - | Insulin glargine is a hormone protein consisting of 52 amino acids in an asymmetric unit. It has two unique chains, chain A and B. The structure was determined by X-ray diffraction and was measured at a resolution of 1.66 Angstroms. Chain A is 21 amino acids long and consists of two alpha helices and one beta sheet. It is modified from normal insulin by the substitution of asparagine for glycine at the twenty first amino acid of the chain. It also has an L-cystine protein modification at amino acids C6 and C11 of the chain. <ref name="four">Barba de la Rosa, A. P., Lara-Gonzalez, S., Montero-Moran, G. M., Escobedo-Moratilla, A., and Perez-Urizar, J.T. Physiochemical and structural analysis of a biosimilar insulin glargine formulation and its reference. In Press.</ref> This modification is in which a disulfide bond is formed between the side chains of two cysteine residues within the amino acid chain via an oxidation reaction. <ref name="five">Gortner, R. A., & Hoffmann, W. F. (1925). l-Cystine. Organic Syntheses, 5, 39.</ref> | + | Insulin glargine is a hormone protein consisting of 52 amino acids in an asymmetric unit. It has two unique chains, chain A and B. The structure was determined by X-ray diffraction and was measured at a resolution of 1.66 Angstroms. Chain A is 21 amino acids long and consists of two alpha helices and one beta sheet. It is modified from normal insulin by the substitution of asparagine for glycine at the twenty first amino acid of the chain. It also has an L-cystine protein modification at amino acids C6 and C11 of the chain.<ref name="four">Barba de la Rosa, A. P., Lara-Gonzalez, S., Montero-Moran, G. M., Escobedo-Moratilla, A., and Perez-Urizar, J.T. Physiochemical and structural analysis of a biosimilar insulin glargine formulation and its reference. In Press.</ref> This modification is in which a disulfide bond is formed between the side chains of two cysteine residues within the amino acid chain via an oxidation reaction.<ref name="five">Gortner, R. A., & Hoffmann, W. F. (1925). l-Cystine. Organic Syntheses, 5, 39.</ref> |
| - | Chain B is 31 amino acids long and consists of two alpha helices and one beta sheet. <ref name="four">Barba de la Rosa, A. P., Lara-Gonzalez, S., Montero-Moran, G. M., Escobedo-Moratilla, A., and Perez-Urizar, J.T. Physiochemical and structural analysis of a biosimilar insulin glargine formulation and its reference. In Press.</ref><ref name="six">Agin, A., Jeandidier, N., Gasser, F., Grucker, F., and Sapin, R. (2007) Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay, Diabetes and Metabolism 33, 205-212</ref> It is modified from normal insulin by the addition of two arginine residues to the C-terminus of the chain. <ref name="six">Agin, A., Jeandidier, N., Gasser, F., Grucker, F., and Sapin, R. (2007) Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay, Diabetes and Metabolism 33, 205-212</ref> These modifications raise the isoelectric point (pI) from 5.4 to 6.7, improving solubility under mildly acidic conditions <ref name="seven">Bolli, G. B. & Owens, D. R. (2000). Insulin glargine. The Lancet, 356(9228), 443-445.</ref> | + | Chain B is 31 amino acids long and consists of two alpha helices and one beta sheet.<ref name="four">Barba de la Rosa, A. P., Lara-Gonzalez, S., Montero-Moran, G. M., Escobedo-Moratilla, A., and Perez-Urizar, J.T. Physiochemical and structural analysis of a biosimilar insulin glargine formulation and its reference. In Press.</ref><ref name="six">Agin, A., Jeandidier, N., Gasser, F., Grucker, F., and Sapin, R. (2007) Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay, Diabetes and Metabolism 33, 205-212</ref> It is modified from normal insulin by the addition of two arginine residues to the C-terminus of the chain.<ref name="six">Agin, A., Jeandidier, N., Gasser, F., Grucker, F., and Sapin, R. (2007) Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay, Diabetes and Metabolism 33, 205-212</ref> These modifications raise the isoelectric point (pI) from 5.4 to 6.7, improving solubility under mildly acidic conditions.<ref name="seven">Bolli, G. B. & Owens, D. R. (2000). Insulin glargine. The Lancet, 356(9228), 443-445.</ref> |
| - | These two chains are held together by disulfide bonds formed between cysteine side chains on opposing chains. One disulfide bond is formed between the cysteine residues at amino acid seven of chain A and amino acid seven of chain B. Another disulfide bond is formed between the cysteine residues at amino acid 21 of chain A and amino acid 19 of chain B. <ref name="six">Agin, A., Jeandidier, N., Gasser, F., Grucker, F., and Sapin, R. (2007) Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay, Diabetes and Metabolism 33, 205-212</ref> | + | These two chains are held together by disulfide bonds formed between cysteine side chains on opposing chains. One disulfide bond is formed between the cysteine residues at amino acid seven of chain A and amino acid seven of chain B. Another disulfide bond is formed between the cysteine residues at amino acid 21 of chain A and amino acid 19 of chain B.<ref name="six">Agin, A., Jeandidier, N., Gasser, F., Grucker, F., and Sapin, R. (2007) Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay, Diabetes and Metabolism 33, 205-212</ref> |
These disulfide linkages, general structure of insulin glargine, and its sequence differences with normal human insulin are shown by a [http://www.sciencedirect.com/science/article/pii/S1262363607000523#fig1 figure] presented by Agin et. al.<ref name="six">Agin, A., Jeandidier, N., Gasser, F., Grucker, F., and Sapin, R. (2007) Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay, Diabetes and Metabolism 33, 205-212</ref> | These disulfide linkages, general structure of insulin glargine, and its sequence differences with normal human insulin are shown by a [http://www.sciencedirect.com/science/article/pii/S1262363607000523#fig1 figure] presented by Agin et. al.<ref name="six">Agin, A., Jeandidier, N., Gasser, F., Grucker, F., and Sapin, R. (2007) Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay, Diabetes and Metabolism 33, 205-212</ref> | ||
== Mechanism == | == Mechanism == | ||
| - | The affinity of insulin glargine for the receptor insulin is very similar to the affinity of human insulin for insulin, and has been documented by multiple reports. <ref name="eight">Ciaraldi, T. P., Carter, L., Seipke, G., Mudaliar, S., & Henry, R. R. (2001). Effects of the long-acting insulin analog insulin glargine on cultured human skeletal muscle cells: comparisons to insulin and IGF-I. The Journal of Clinical Endocrinology & Metabolism, 86(12), 5838-5847.</ref> Insulin glargine’s mechanism is akin to [http://proteopedia.org/wiki/index.php/Insulin human insulin’s] mechanism. <ref name="one">McKeage, K., & Goa, K. L. (2001). Insulin glargine. Drugs, 61(11), 1599-1624.</ref> It has been shown that after subcutaneous injection of glargine, it becomes metabolized into M1 (A21-Gly-insulin) and M2 (A21-Gly-des-30B-Thr-insulin); M1 has been found to be the pharmacologically active metabolite of glargine. <ref name="nine">Kuerzel, G. U., Shukla, U., Scholtz, H. E.,Pretorius, S. G., Wessels, D. H., Venter, C., Potgieter, M. A., Lang, A. M., Koose, T. & Bernhardt, E. (2003). Biotransformation of insulin glargine after subcutaneous injection in healthy subjects, Current Medical Research and Opinion, 19:1, 34-40.</ref><ref name="ten">Lucidi, P., Porcellati, F., Candeloro, P., Cioli, P., Marinelli Andreoli, A., Marzotti, S., Schmidt, R., Bolli, G.B. & Fanelli, C.G. (2014). Glargine metabolism over 24 h following its subcutaneous injection in patients with type 2 diabetes mellitus: A dose response study. Nutrition, Metabolism & Cardiovascular Diseases, 24, 709-716.</ref> | + | The affinity of insulin glargine for the receptor insulin is very similar to the affinity of human insulin for insulin, and has been documented by multiple reports.<ref name="eight">Ciaraldi, T. P., Carter, L., Seipke, G., Mudaliar, S., & Henry, R. R. (2001). Effects of the long-acting insulin analog insulin glargine on cultured human skeletal muscle cells: comparisons to insulin and IGF-I. The Journal of Clinical Endocrinology & Metabolism, 86(12), 5838-5847.</ref> Insulin glargine’s mechanism is akin to [http://proteopedia.org/wiki/index.php/Insulin human insulin’s] mechanism.<ref name="one">McKeage, K., & Goa, K. L. (2001). Insulin glargine. Drugs, 61(11), 1599-1624.</ref> It has been shown that after subcutaneous injection of glargine, it becomes metabolized into M1 (A21-Gly-insulin) and M2 (A21-Gly-des-30B-Thr-insulin); M1 has been found to be the pharmacologically active metabolite of glargine.<ref name="nine">Kuerzel, G. U., Shukla, U., Scholtz, H. E.,Pretorius, S. G., Wessels, D. H., Venter, C., Potgieter, M. A., Lang, A. M., Koose, T. & Bernhardt, E. (2003). Biotransformation of insulin glargine after subcutaneous injection in healthy subjects, Current Medical Research and Opinion, 19:1, 34-40.</ref><ref name="ten">Lucidi, P., Porcellati, F., Candeloro, P., Cioli, P., Marinelli Andreoli, A., Marzotti, S., Schmidt, R., Bolli, G.B. & Fanelli, C.G. (2014). Glargine metabolism over 24 h following its subcutaneous injection in patients with type 2 diabetes mellitus: A dose response study. Nutrition, Metabolism & Cardiovascular Diseases, 24, 709-716.</ref> |
== Medical Use == | == Medical Use == | ||
| - | Insulin glargine functions as an insulin analogue, providing basal control of glycaemia for patients with Type 1 and Type 2 diabetes. <ref name="one">McKeage, K., & Goa, K. L. (2001). Insulin glargine. Drugs, 61(11), 1599-1624.</ref>The pH 4 glargine solution is subcutaneously injected to form a microprecipitate in physiological pH.The effectiveness of glargine is dampened when mixed with more neutral insulins due to resulting disruption of precipitate formation. <ref name="eleven">Havelund, S., Plum, A., Ribel, U., Jonassen, I., Vølund, A., Markussen, J., & Kurtzhals, P. (2004). The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharmaceutical research, 21(8), 1498-1504.</ref> Insulin glargine’s | + | Insulin glargine functions as an insulin analogue, providing basal control of glycaemia for patients with Type 1 and Type 2 diabetes.<ref name="one">McKeage, K., & Goa, K. L. (2001). Insulin glargine. Drugs, 61(11), 1599-1624.</ref>The pH 4 glargine solution is subcutaneously injected to form a microprecipitate in physiological pH.The effectiveness of glargine is dampened when mixed with more neutral insulins due to resulting disruption of precipitate formation.<ref name="eleven">Havelund, S., Plum, A., Ribel, U., Jonassen, I., Vølund, A., Markussen, J., & Kurtzhals, P. (2004). The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharmaceutical research, 21(8), 1498-1504.</ref> Insulin glargine’s stability allows the formed microprecipitate to be slowly administered simulating non-diabetic basal insulin secretion.<ref name="seven">Bolli, G. B. & Owens, D. R. (2000). Insulin glargine. The Lancet, 356(9228), 443-445.</ref> This enables insulin glargine to be an extended release insulin treatment administered once per day. |
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 01:26, 30 March 2017
Insulin Glargine
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References
- ↑ 1.0 1.1 1.2 McKeage, K., & Goa, K. L. (2001). Insulin glargine. Drugs, 61(11), 1599-1624.
- ↑ 2.0 2.1 2.2 Baeshen, N. A., Baeshen, M. N., Sheikh, A., Bora, R. S., Ahmed, M. M. M., Ramadan, H. A., ... & Redwan, E. M. (2014). Cell factories for insulin production. Microbial cell factories, 13(1), 141.
- ↑ Walsh, G. (2005). Therapeutic insulins and their large-scale manufacture. Applied microbiology and biotechnology, 67(2), 151-159.
- ↑ 4.0 4.1 Barba de la Rosa, A. P., Lara-Gonzalez, S., Montero-Moran, G. M., Escobedo-Moratilla, A., and Perez-Urizar, J.T. Physiochemical and structural analysis of a biosimilar insulin glargine formulation and its reference. In Press.
- ↑ Gortner, R. A., & Hoffmann, W. F. (1925). l-Cystine. Organic Syntheses, 5, 39.
- ↑ 6.0 6.1 6.2 6.3 Agin, A., Jeandidier, N., Gasser, F., Grucker, F., and Sapin, R. (2007) Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay, Diabetes and Metabolism 33, 205-212
- ↑ 7.0 7.1 Bolli, G. B. & Owens, D. R. (2000). Insulin glargine. The Lancet, 356(9228), 443-445.
- ↑ Ciaraldi, T. P., Carter, L., Seipke, G., Mudaliar, S., & Henry, R. R. (2001). Effects of the long-acting insulin analog insulin glargine on cultured human skeletal muscle cells: comparisons to insulin and IGF-I. The Journal of Clinical Endocrinology & Metabolism, 86(12), 5838-5847.
- ↑ Kuerzel, G. U., Shukla, U., Scholtz, H. E.,Pretorius, S. G., Wessels, D. H., Venter, C., Potgieter, M. A., Lang, A. M., Koose, T. & Bernhardt, E. (2003). Biotransformation of insulin glargine after subcutaneous injection in healthy subjects, Current Medical Research and Opinion, 19:1, 34-40.
- ↑ Lucidi, P., Porcellati, F., Candeloro, P., Cioli, P., Marinelli Andreoli, A., Marzotti, S., Schmidt, R., Bolli, G.B. & Fanelli, C.G. (2014). Glargine metabolism over 24 h following its subcutaneous injection in patients with type 2 diabetes mellitus: A dose response study. Nutrition, Metabolism & Cardiovascular Diseases, 24, 709-716.
- ↑ Havelund, S., Plum, A., Ribel, U., Jonassen, I., Vølund, A., Markussen, J., & Kurtzhals, P. (2004). The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharmaceutical research, 21(8), 1498-1504.
