O5 HTD4010, an INGAP-PP analoguewith a more potenteffectonmodulation of β-cellmass and function

Abstract

Background: INGAP-PP, a 15-amino acidpeptidederivedfrom INGAP (IsletNeogenesisAssociatedProtein), positivelymodulates β-cellmass and function in normal and diabeticrats. In a clinical trial, INGAP-PP increased C-peptiderelease in peoplewith DT1 and improvedglycaemic control on DT2 patients, butthestudyhad to be stoppeddue to theappearance of skin lesions at theinjectionsite. Lookingfor more stable and potentanalogues, able of beingadministered in lowerconcentrationswith a reducedinjectionfrequency, HTD4010, a peptidethat shows greaterstability in plasma, has beendeveloped. Aim: to determine theeffect of HTD4010 oninsulinsecretion and gene expression of modulatorfactors of β cellsmass and function. Materials and methods:Isolatedislets (digestionwithcollagenase) from normal maleWistarratswereculturedfor 4 days in RPMI, without (Control group -C-) orwiththeaddition to the culture medium of 1 µg/ml INGAP-PP (I1), or HTD4010 at differentconcentrations: 0.01 (H0.01); 0.1 (H0.1) or 1 µg/ml (H1). Groups of 5 pre-culturedisletswereincubatedforonehour in KRB withdifferentglucoseconcentrations (3.3 or 16.6 mM) and insulinreleasedwasdeterminedby RIA. Total RNA wasobtainedfrom C, I1 and H0.01 islets and gene expressionlevels of markers of insulinsignalling and β-cellmass (neogenesis and apoptosis) and functionweredeterminedby RT-qPCR.

Keywords

• péptido análogo
• ingap-pp
• masa insular ß.