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Rapid changes in the microvascular circulation of skeletal muscle impair insulin
delivery during sepsis.
Authors Mignemi NA, McClatchey PM, Kilchrist KV, Williams IM, Millis BA, Syring KE,
Duvall CL, Wasserman DH, McGuinness OP
Submitted By Submitted Externally on 5/13/2019
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2019
Date Published 3/1/2019
Volume : Pages Not Specified : Not Specified
PubMed Reference 30860883
Abstract Sepsis costs the healthcare system $23 billion annually and has a mortality rate
between 10-40%. An early indication of sepsis is the onset of hyperglycemia,
which is the result of sepsis-induced insulin resistance in skeletal muscle.
Previous investigations have focused on events in the myocyte (e.g. insulin
signaling and glucose transport and subsequent metabolism) as the causes for
this insulin resistant state. However, the delivery of insulin to the skeletal
muscle is also an important determinant of insulin action. Skeletal muscle
microvascular blood flow, which delivers the insulin to the muscle, is known to
be decreased during sepsis. Here we test whether the reduced capillary blood
flow to skeletal muscle belies the sepsis-induced insulin resistance by reducing
insulin delivery to the myocyte. We hypothesize that decreased capillary flow
and consequent decrease in insulin delivery is an early event that precedes
gross cardiovascular alterations seen with sepsis. This hypothesis was examined
in mice treated with either lipopolysaccharide (LPS) or polymicrobial sepsis
followed by intravital microscopy of the SkM microcirculation. We calculated
insulin delivery to the myocyte using two independent methods and found that LPS
and sepsis rapidly reduce insulin delivery to the skeletal muscle by ~50%; this
was driven by decreases in capillary flow velocity and the number of perfused
capillaries. Further, the changes in skeletal muscle microcirculation occur
prior to changes in both cardiac output and arterial blood pressure. These data
suggest that a rapid reduction in skeletal muscle insulin delivery contributes
to the induction of insulin resistance during sepsis.


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