Type:Protein
SpeciesReactivity:H;R
B=Bovine;Ca=Cat;Ch=Chicken;D=Dog;EQ=Equine;GP=GuineaPig;H=Human;M=Mouse;P=Porcine;Pr=Primate;R=Rat;Rb=Rabbit;Y=Yeast;Xe=Xenopus;Ze=Zebrafish;;;;NA-NotApplicable;STP=Step-TactinProteins;Allpro-Insulinissynthesizedasasinglechain,110aminoacid(aa)preproprecursorthatcontainsa24aasignalsequenceandan86aaproinsulinpropeptide.Followingremovalofthesignalpeptide,thepro-insulinpeptideundergoesfurtherproteolysistogeneratematureinsulin,a51aadisulfidelinkeddimerthatconsistsofa30aaBchain(aa2554)boundtoa21aaAchain(aa90110).The34aainterveningpeptide(aa5589)thatconnectstheBandAchainsistermedtheC-peptide.HumanproIinsulinshares84%and80%aasequenceidentitywiththeratandbovineprotein,respectively.MostofthesequencevariationbetweenspeciesoccursintheregionoftheC-peptide(1).
Thispeptidegeneratesastructuralconformationthatallowsforthecorrectformationoftheintrachaindisulphidebonds(1).Insulinisamoleculethatfacilitatesthecellularuptakeofglucose.Thisisaccomplishedbyregulatingtheappearanceofmembraneglucosetransporters.Lowinsulinlevelsorlackofinsulinareassociatedwithtype2andtype1diabetesmellitus,respectively.Theseconditionsareassociatedwithanincreasedriskformicrovascularcomplicationssuchasretinopathy,nephropathy,andperipheralneuropathy(3).pro-Insulinalsocirculates,butitsphysiologicroleislesswellunderstood.Itdoespossessabout25%oftheactivityofmatureinsulin,butitwouldseemunlikelytobeanaturalsubstituteforinsulin(4).Intype2diabetes,anelevatedpro-insulintoinsulinratiointhecirculationisawellknownabnormality(59).PerhapsthisabnormalityrepresentseithercompromisedproteolyticprocessingorageneralinABIlitytoprocessincreasedlevelsofinsulinprecursor(5).Inanyevent,pro-insulinwillstimulateamylinsecretionbyβ-cells,andamyloidformationinpancreaticisletsthatpromotesdecreasedβcellfunction(10).Studiesalsosuggestthatfastingserumproinsulinmaybeabetterpredictoroffuturetype2diabetesthanfastinginsulinlevelsinobesechildren(11).
