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Diabetes, Vol 44, Issue 11 1310-1317, Copyright © 1995 by American Diabetes Association
Elevation of serum insulin concentration during euglycemic hyperinsulinemic clamp studies leads to similar activation of insulin receptor kinase in skeletal muscle of subjects with and without NIDDM
HH Klein, H Vestergaard, G Kotzke and O Pedersen
Department of Internal Medicine, Medizinische Universitat zu Lubeck, Germany.
The role of skeletal muscle insulin receptor kinase in the pathogenesis of
non-insulin-dependent diabetes mellitus (NIDDM) was investigated. Muscle
biopsies from 13 patients with NIDDM and 10 control subjects at fasting
serum insulin concentrations and approximately 1,000 pmol/l steady-state
serum insulin during euglycemic hyperinsulinemic clamps were immediately
frozen. The biopsies were then solubilized, and the receptors were
immobilized to anti-insulin receptor antibody-coated microwells. Receptor
kinase and binding activities were consecutively measured in these wells.
The increase in serum insulin concentration (73 +/- 14 to 1,004 +/- 83 and
45 +/- 7 to 1,07 +/- 77 pmol/l in the NIDDM and control groups,
respectively) had similar effects on receptor kinase activity in both study
groups (12 +/- 1 to 42 +/- 5 and 12 +/- 2 to 47 +/- 5 amol P.fmol binding
activity-1. min-1 in the NIDDM and control groups, respectively). Moreover,
by selecting only the receptors that bound to anti-phosphotyrosine
antibody, we found similar hyperinsulinemia-induced increases of this
receptor fraction and its kinase activity in both study groups. In vitro
activation of the immobilized receptors with 2 mmol/l ATP and insulin
further increased their kinase activity to almost similar levels,
independently of whether they had been previously stimulated in vivo or
were from diabetic or nondiabetic subjects. Compared with this activity
reached in vitro, the kinase activity obtained by in vivo stimulation at
the clamp insulin concentration was only approximately 12%, because most
receptors remained inactive and only a few reached almost the in vitro
activation level.(ABSTRACT TRUNCATED AT 250 WORDS)

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Copyright © 1995 by the American Diabetes Association.
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