Proinsulin: Difference between revisions
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== Immunogenicity == |
== Immunogenicity == |
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When insulin was originally purified from [[bovine]] or [[porcine]] pancreata, all the proinsulin was not fully removed.<ref name=Purified>{{cite |
When insulin was originally purified from [[bovine]] or [[porcine]] pancreata, all the proinsulin was not fully removed.<ref name=Purified>{{cite journal | author = Wilson RM, Douglas CA, Tattersall RB, Reeves WG | title = Immunogenicity of highly purified bovine insulin: a comparison with conventional bovine and highly purified human insulins | journal = Diabetologia | volume = 28 | issue = 9 | pages = 667–70 | year = 1985 | month = September | pmid = 3905477 | doi = }}</ref><ref name=Endotext>{{cite web | url = http://www.endotext.org/diabetes/diabetes17/diabetes17.htm | title = Insulin Pharmacology, Type of Regimens and Adjustments | author = Tanyolac S, Goldfine ID, Kroon L | authorlink = | coauthors = | date = | format = | work = | publisher = Endotext.com | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2011-03-18 }}</ref> When some people used these insulins, the proinsulin may have caused the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin was injected. This can be described as an [[iatrogenic]] injury due to slight differences between the proinsulin of different species.<!-- The differences are in the amino acid composition of the respective insulins. While some skin injuries were due to the non-highly purified insulins cauing immunogenic reactions, these issues are still present due to various poor injection techniques, and can occur with any that is poorly used. http://www.endocrine-abstracts.org/ea/0012/ea0012p40.htm These same amino acid differences in insulin species can cause longer duration which can be a "positive" aspect in some cases. Bovine Ultralente is peakless and lasts longer than Lantus because of this<ref name="pmid3698778">{{cite journal | author = Rizza RA, O'Brien PC, Service FJ | title = Use of beef ultralente for basal insulin delivery: plasma insulin concentrations after chronic ultralente administration in patients with IDDM | journal = Diabetes Care | volume = 9 | issue = 2 | pages = 120–3 | year = 1986 | pmid = 3698778 | doi = | url = | issn = }}</ref> But I question whether this belongs on a page about proinsulin.--> Since the late 1970s, when highly-purified [[porcine]] insulin was introduced, and the level of insulin purity reached 99%, this ceased to be a significant clinical issue.<ref name="pmid6756879">{{cite journal | author = Home PD, Alberti KG | title = The new insulins. Their characteristics and clinical indications | journal = Drugs | volume = 24 | issue = 5 | pages = 401–13 | year = 1982 | month = November | pmid = 6756879 | doi = }}</ref> It should also be noted that in respect of their influence on insulin pharmacokinetics, moderate concentrations of certain insulin antibodies may, in fact, be of positive advantage to all diabetics without endogenous insulin secretion (e.g. people with [[type 1 diabetes]]) because insulin binding antibodies effectively increase the insulin's clearance rate and distribution space and therefore helps to prolong its pharmacological and biological half lives.<ref name="pmid3924216">{{cite journal | author = Gray RS, Cowan P, di Mario U, Elton RA, Clarke BF, Duncan LJ | title = Influence of insulin antibodies on pharmacokinetics and bioavailability of recombinant human and highly purified beef insulins in insulin dependent diabetics | journal = Br Med J (Clin Res Ed) | volume = 290 | issue = 6483 | pages = 1687–91 | year = 1985 | month = June | pmid = 3924216 | pmc = 1416075 | doi = 10.1136/bmj.290.6483.1687| url = | issn = }}</ref>{{Clarify|date=August 2009}} |
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== See also == |
== See also == |
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Revision as of 07:11, 19 March 2011
| insulin | |||||||
|---|---|---|---|---|---|---|---|
 Insulin undergoes extensive posttranslational modification along the production pathway. Production and secretion are largely independent; prepared insulin is stored awaiting secretion. Both C-peptide and mature insulin are biologically active. Cell components and proteins in this image are not to scale. | |||||||
| Identifiers | |||||||
| Symbol | INS | ||||||
| NCBI gene | 3630 | ||||||
| HGNC | 6081 | ||||||
| OMIM | 176730 | ||||||
| RefSeq | NM_000207 | ||||||
| UniProt | P01308 | ||||||
| Other data | |||||||
| Locus | Chr. 11 p15.5 | ||||||
| |||||||
Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. In humans, proinsulin is encoded by the INS gene.[1][2]
Synthesis and post-translational modification
Proinsulin is synthesized in the endoplasmic reticulum, where it is folded and its disulfide bonds are oxidized. It is then transported to the Golgi apparatus where it is packaged into secretory vesicles, and where it is processed by a series of proteases to form mature insulin. Mature insulin has 35 fewer amino acids; 4 are removed altogether, and the remaining 31 form the C-peptide. The C-peptide is abstracted from the center of the proinsulin sequence; the two other ends (the B chain and A chain) remain connected by disulfide bonds.
Immunogenicity
When insulin was originally purified from bovine or porcine pancreata, all the proinsulin was not fully removed.[3][4] When some people used these insulins, the proinsulin may have caused the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin was injected. This can be described as an iatrogenic injury due to slight differences between the proinsulin of different species. Since the late 1970s, when highly-purified porcine insulin was introduced, and the level of insulin purity reached 99%, this ceased to be a significant clinical issue.[5] It should also be noted that in respect of their influence on insulin pharmacokinetics, moderate concentrations of certain insulin antibodies may, in fact, be of positive advantage to all diabetics without endogenous insulin secretion (e.g. people with type 1 diabetes) because insulin binding antibodies effectively increase the insulin's clearance rate and distribution space and therefore helps to prolong its pharmacological and biological half lives.[6][clarification needed]
See also
- insulin
- signal peptide, signal peptide peptidase, preproinsulin
- proprotein convertase 1, proprotein convertase 2
References
- ^ "Entrez Gene: INS insulin".
- ^ Bell GI, Pictet RL, Rutter WJ, Cordell B, Tischer E, Goodman HM (1980). "Sequence of the human insulin gene". Nature. 284 (5751): 26–32. doi:10.1038/284026a0. PMID 6243748.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Wilson RM, Douglas CA, Tattersall RB, Reeves WG (1985). "Immunogenicity of highly purified bovine insulin: a comparison with conventional bovine and highly purified human insulins". Diabetologia. 28 (9): 667–70. PMID 3905477.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Tanyolac S, Goldfine ID, Kroon L. "Insulin Pharmacology, Type of Regimens and Adjustments". Endotext.com. Retrieved 2011-03-18.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help)CS1 maint: multiple names: authors list (link) - ^ Home PD, Alberti KG (1982). "The new insulins. Their characteristics and clinical indications". Drugs. 24 (5): 401–13. PMID 6756879.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Gray RS, Cowan P, di Mario U, Elton RA, Clarke BF, Duncan LJ (1985). "Influence of insulin antibodies on pharmacokinetics and bioavailability of recombinant human and highly purified beef insulins in insulin dependent diabetics". Br Med J (Clin Res Ed). 290 (6483): 1687–91. doi:10.1136/bmj.290.6483.1687. PMC 1416075. PMID 3924216.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)