Prolonged near-physiological pulsatile insulin infusion has a greater hypoglycemie effect than continuous insulin infusion. We have previously shown that continuous hyperinsulinemia induces insulin insensitivity. This study examines the mechanisms responsible for the greater hypoglycemie effect of pulsatile insulin administration, in particular, whether prolonged pulsatile hyperinsulinemia induces insulin insensitivity. Basally and 1 h after cessation of a 20-h pulsatile infusion of insulin (0.5 mU · kg−1 · min−1), eight nondiabetic human subjects were assessed for 1) glucose turnover with [3-3H]glucose, 2) insulin sensitivity by minimal-model analysis of intravenous glucose tolerance tests, and 3) monocyte insulin-receptor binding. The time-averaged plasma insulin levels were 30 ± 5 mU/L (mean ± SE) during the infusion, which was similar to the levels achieved in our previous continuous hyperinsulinemia study. However, the average rate of glucose infusion to maintain euglycemia was 55% greater than in the previous study. Hepatic glucose production was -5.2 ±1.4 μmol · kg −1 · min−1 during the infusion but returned to preinfusion levels 1 h after the infusion was stopped. Insulin sensitivity (Si) and glucose tolerance (rate of glucose disappearance, Kg) showed changes opposite in direction to our previous continuous hyperinsulinemia study (pre- vs. postinfusion Kg 1.5 ± 0.1 vs. 1.7 ± 0.2 min−1 × 102, NS; pre- vs. postinfusion S, 8.4 ± 2.3 vs. 11.8 ± 3.7 min−1 · mU1 · L × 104 P < 0.05). There was no change in glucose-mediated glucose disposal (2.0 ± 0.2 vs. 2.3 ± 0.4 min−1 × 102) or pancreatic β-cell responsiveness (1st phase, 1.8 ± 0.2 vs. 2.2 ± 0.4 μU · ml−1 · min−1 · mg−1 · dl; 2nd phase, 9.9 ± 1.0 vs. 16.6 ± 3.5 μU · ml−1 · min∼−2 · mg−1 · dl). Monocyte insulin-receptor binding showed a postinfusion decrease. Plasma nonesterified fatty acids were profoundly suppressed during the infusion (0.05 ± 0.01 mM) and remained significantly (P < 0.05) suppressed 1 h postinfusion (0.21 ± 0.06 mM) compared with preinfusion (0.54 ± 0.08 mM). We conclude that despite a reduction in monocyte insulin-receptor binding, prolonged moderate pulsatile hyperinsulinemia, in contrast to equivalent continuous hyperinsulinemia, induced enhancement of insulin sensitivity, causing a greater hypoglycemie effect and greater suppression of plasma nonesterified-fatty acid levels.
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Original Articles|
April 01 1990
Effects of Prolonged Pulsatile Hyperinsulinemia in Humans: Enhancement of Insulin Sensitivity
Glenn M Ward;
Glenn M Ward
Endocrine Unit and University of Melbourne Department of Medicine, St. Vincent's Hospital, Fitzroy
Victoria, Australia
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Jacqueline M Walters;
Jacqueline M Walters
Endocrine Unit and University of Melbourne Department of Medicine, St. Vincent's Hospital, Fitzroy
Victoria, Australia
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Patricia M Aitken;
Patricia M Aitken
Endocrine Unit and University of Melbourne Department of Medicine, St. Vincent's Hospital, Fitzroy
Victoria, Australia
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James D Best;
James D Best
Endocrine Unit and University of Melbourne Department of Medicine, St. Vincent's Hospital, Fitzroy
Victoria, Australia
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Frank P Alford
Frank P Alford
Endocrine Unit and University of Melbourne Department of Medicine, St. Vincent's Hospital, Fitzroy
Victoria, Australia
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Address correspondence and reprint requests to Dr. G. M. Ward, Endocrine Unit, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.
Diabetes 1990;39(4):501–507
Article history
Received:
December 21 1988
Revision Received:
November 29 1989
Accepted:
November 29 1989
PubMed:
2180760
Citation
Glenn M Ward, Jacqueline M Walters, Patricia M Aitken, James D Best, Frank P Alford; Effects of Prolonged Pulsatile Hyperinsulinemia in Humans: Enhancement of Insulin Sensitivity. Diabetes 1 April 1990; 39 (4): 501–507. https://doi.org/10.2337/diab.39.4.501
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