Editing Proinsulin (section)

== Immunogenicity ==

When insulin was originally purified from [[bovine]] or [[porcine]] pancreata, all the proinsulin was not fully removed.<ref name=Purified>{{cite journal | vauthors = 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 | date = September 1985 | pmid = 3905477 | doi = 10.1007/BF00291973 | doi-access = free }}</ref><ref name=Endotext>{{cite web | url = http://www.endotext.org/diabetes/diabetes17/diabetes17.htm | title = Insulin Pharmacology, Type of Regimens and Adjustments | vauthors = Tanyolac S, Goldfine ID, Kroon L | date =  | website =  | publisher = Endotext.com | access-date = 2011-03-18 | archive-url = https://web.archive.org/web/20110725130334/http://www.endotext.org/diabetes/diabetes17/diabetes17.htm | archive-date = 2011-07-25 | url-status = dead }}</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 causing 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 | vauthors = 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 = 10.2337/diacare.9.2.120 }}</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 | vauthors = Home PD, Alberti KG | title = The new insulins. Their characteristics and clinical indications | journal = Drugs | volume = 24 | issue = 5 | pages = 401–13 | date = November 1982 | pmid = 6756879 | doi = 10.2165/00003495-198224050-00003 | s2cid = 28616749 | url = https://www.semanticscholar.org/paper/05663202b5ffa42441c735516788e4fa9eeece68 }}</ref> With respect to their influence on insulin pharmacokinetics, moderate concentrations of certain insulin antibodies may 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 help to prolong its pharmacological and biological half lives.<ref name="pmid3924216">{{cite journal | vauthors = 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 = British Medical Journal | volume = 290 | issue = 6483 | pages = 1687–91 | date = June 1985 | pmid = 3924216 | pmc = 1416075 | doi = 10.1136/bmj.290.6483.1687 }}</ref>{{Clarify|date=August 2009}}