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Abstract
The monomeric insulin analogue insulin lispro (Lys B28, Pro B29) is a rapid-acting
insulin with a shorter duration of activity than human regular insulin. This compound
has the advantage of reducing early postprandial hyperglycemia and the accompanying
late hypoglycemia, thereby improving overall blood glucose control. To date, all published
studies of the functional properties of insulin lispro have been conducted in whole
animals. This study aimed to characterize the cellular actions of insulin lispro and
the signals it elicits in an insulin-sensitive muscle cell line, L6 cells. Comparing
the cellular actions of insulin lispro with those of human regular insulin, a number
of observations were made. (1) Insulin lispro stimulated glucose and amino acid transport
into L6 myotubes with a dose dependency and time course virtually identical to those
of human regular insulin. (2) Insulin lispro was as effective as human regular insulin
in stimulating time-dependent phosphorylation of insulin receptor substrate 1 (IRS-1),
p70 ribosomal S6 kinase, and two isoforms of mitogen-activated protein kinase (ERK1
and ERK2). (3) Insulin lispro's ability to induce the association of IRS-1 with the
p85 subunit of phosphatidylinositol 3-kinase was similar to that of human regular
insulin. (4) As with human regular insulin, 100 nmol of the fungal metabolite wortmannin
completely inhibited insulin lispro stimulation of glucose uptake. We concluded that
the cellular actions of insulin lispro are similar to those of human regular insulin
with respect to glucose and amino acid uptake and that the biochemical signals elicited
are also comparable.
Keywords
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© 1998 Published by Elsevier Inc.
