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Articles in PresS, published online ahead of print December 18, 2001
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00427.2001
Submitted on September 24, 2001
Accepted on December 4, 2001
1 The Clinical Research Unit of Gastrointestinal Endocrinology, Department of Internal Medicine, Philipps University Marburg, Marburg, Germany
2 Novo Nordisk, Bagsvaerd, Denmark
3 Department of Gastroenterology, Ludwig-Maximilians-University, Munich, Germany
* To whom correspondence should be addressed. E-mail: byrne{at}uni-muenster.de.
Impaired glucose tolerance (IGT) and non-insulin dependent diabetes mellitus (NIDDM) are associated with an impaired ability of the ß-cell to sense and respond to small changes in plasma glucose. The aim of this study was to establish if acute hyperglycemia per se, plays a role in inducing this defect in ß-cell response. Seven healthy volunteers with no family history of NIDDM were studied on two occasions during a 12-h oscillatory glucose infusion, with a periodicity of 144 min. Once, low-dose glucose was infused at a mean rate of 6 mg/kg/min and amplitude 33 % above and below the mean rate, and once high-dose glucose was infused at 12 mg/kg/min and amplitude 16 % above and below the mean rate. Mean glucose levels were significantly higher during the high-dose compared to the low-dose glucose infusion 9.5±0.8 vs 6.8±0.2 mM; P<0.01, resulting in increased mean insulin secretion rates (ISRs) 469.1±43.8 vs 268.4±29 pmol/min;P<0.001, and mean insulin levels 213.6±46 vs 67.9±10.9 pmol/L;P<0.008. Spectral analysis evaluates the regularity of oscillations in glucose, insulin secretion and insulin at a predetermined frequency. Spectral power for glucose, ISR and insulin was reduced during the high-dose glucose infusion 11.8±1.4 to 7.0±1.6 (P<0.02), 7.6±1.5 to 3.2±0.5 (P<0.04) and 10.5±1.6 to 4.6±0.7 (P<0.01) respectively. In conclusion, short term infusion of high-dose glucose to obtain glucose levels similar to those previously seen in IGT subjects results in reduced spectral power for glucose, ISR and insulin. The reduction in spectral power previously observed for ISR in IGT or NIDDM subjects may be due partly to hyperglycemia.
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