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Abstract
It has previously been shown that in normal subjects, physiological elevation of norepinephrine
(NE) impairs insulin sensitivity (Si) but does not influence insulin secretion. The
aim of this study was to determine the effect of short-term physiological elevation
of NE on insulin secretion, Si, and glucose-mediated glucose disposal, or the glucose
effectiveness index (Sg), in non-insulin-dependent diabetes mellitus (NIDDM). Two
intravenous glucose tolerance tests (IVGTTs) were performed in eight well-controlled
NIDDM patients, using a supplemental exogenous insulin infusion to achieve an approximation
of normal endogenous insulin secretion. The IVGTTs were performed in random order
after 30 minutes of either the saline (SAL) or NE (25 ng/kg/min) infusions, which
were continued throughout the 3-hour IVGTT. Sg and Si were estimated by minimal model
analysis of the IVGTT data as previously described. Plasma C-peptide was used to estimate
insulin secretion rate using the ISEC program. NE infusion produced approximately
a threefold increase in plasma NE, associated with (1) a significant reduction in
glucose disposal ([KG] SAL v NE, 0.73 ± 0.06 v 0.61 ± 0.06 × 10−2 · min−2, P < .05), (2) no reduction in Si (2.33 ± 0.8 v 2.62 ± 0.9 × 10−4 · min−1/mU/L, NS), (3) a reduced mean second-phase insulin secretion rate (1.21 ± 0.19 v 1.01 ± 0.16 × 10−3 pmol/kg/min per mmol/L glucose, P < .05), (4) a significant increase in Sg (0.89 ± 0.08 v 1.63 ± 0.2 × 10−2 · min−1 P < .05), and (5) a corresponding increase in glucose effectiveness at zero insulin
([GEZI] 0.55 ± 0.13 v 1.30 ± 0.33 × 10−2 · min−1, P < .05). These results show that in contrast to normal subjects, physiological elevation
of NE in NIDDM does not result in a reduction in Si, but causes a reduction in glucose
disposal related to inhibition of insulin secretion that is only partially compensated
for by increased Sg.
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Article info
Publication history
Accepted:
June 22,
1997
Received:
January 7,
1997
Footnotes
☆Supported in part by the National Health and Medical Research Council of Australia, St. Vincent's Hospital Research Committee, the National Heart Foundation, and CSL-Novo Nordisk.
Identification
Copyright
© 1997 Published by Elsevier Inc.
