ISSN:
1432-0428
Schlagwort(e):
Intermediate acting insulin
;
biosynthetic human diarginylinsulin
;
insulin receptor binding
;
glucose transport
;
anti-lipolysis
;
protamine allergy
;
proinsulin
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary In diarginylinsulin two arginine residues are located at the C-terminal end of the B-chain (ArgB31 and ArgB32). This accounts for a shift of the isoelectric point from pH 5.4 in native insulin to pH 7.0 in diarginylinsulin leading to pharmacodynamic characteristics of an intermediate acting insulin when administered s. c. as pH 4.0–5.0 solution. We have investigated insulin receptor binding and biological activity of biosynthetic human diarginylinsulin in human adipocytes and compared to native insulin and proinsulin. Association- and dissociation studies of insulin receptor binding revealed no differences for diarginylinsulin and native insulin. In competition studies under steady-state binding conditions, half-maximal displacement of tracer occurred at 352±33 pmol/l, 337±32 pmol/l and 3640±480 pmol/l for diarginylinsulin, insulin and proinsulin, respectively. The biologic potency of human diarginylinsulin was evaluated by the ability to stimulate D-glucose transport and by the assessment of the antilipolytic activity. Activation of D-glucose transport was half-maximal at 49.6±5.4 pmol/l (diarginylinsulin), 44.8±5.8 pmol/l (insulin) and at 476.7±134.3 pmol/l (proinsulin). Half-maximal inhibition of lipolysis occurred at 13.9±3.4 pmol/l, 15.4±2.9 pmol/l and 138.4±38.6 pmol/l, respectively. In conclusion, diarginylinsulin has almost identical insulin receptor binding characteristics and full biological activity in vitro compared to native insulin. This pharmacodynamically intermediate acting insulin preparation is therefore of potential therapeutical value.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00401042
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