Preparation of an insulin with improved pharmacokinetics relative to human insulin through consideration of structural homology with insulin-like growth factor I.
The Diabetes Control and Complications Trial has emphasized the need for improved control of blood glucose as a means to diminish long-term complications of diabetes. LysPro-insulin is an analog of human insulin whose design was modeled on structural homology with insulin-like growth factor I. An analysis of the structural conformation of insulin suggested that an inversion of amino acids B28 and B29 in the C-terminus of the B chain could yield an insulin analog with a faster onset of biological action. This insulin analog has proved to be virtually identical to human insulin in action, with one important exception. LysPro-insulin has demonstrated an improved time course of action in control of a mealtime glucose elevation. This offers the opportunity for improved convenience and safety for patients with insulin-dependent diabetes mellitus.
DiMarchi
R D
RD
Division of Diabetes Research, Lilly Research Laboratories, Indianapolis, IN 46285.
Chance
R E
RE
Long
H B
HB
Shields
J E
JE
Slieker
L J
LJ
D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D007334:Insulin-Like Growth Factor I / Q000737:chemistry*; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017386:Sequence Homology, Amino Acid
D007328:Insulin; D007334:Insulin-Like Growth Factor I