INVIVO NON-INVASIVE MEASUREMENT OF GLUCOSE DYNAMICS APPLICATION OF GLUCOSE CLAMP AND STABLE ISOTOPE

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1. Evaluation of insulin-stimulated glucose disposal by euglycemic hyperinsulinemic clamp combined with oral glucose loading:In order to assess in vivo glucose handlings by peripheral tissues and liver separately, we developed a new noninvasive method applicable to diabetic subjects by combining hyperinsulinemic euglycemic clamp with an oral glucose load. By applying this technique to in non-insulin dependent diabetics, we documented 1) that strict metabolic control by 3 to 4 weeks' intensified insulin therapy significantly augmented hepatic glucose diposal without significant change in insulin sensitivity of peripheral tissues and 2) that hepatic glucose disposal measured 1 hour after moderate-intensity exercise (200 kcal) by a cycle-ergometer significantly increased.2. Application of stable isotope-labeled glucose for the assessment of glucose turnover rates:we applied ^<13>C-glucose as a tracer for the measurement of glucose turnover rates during insulin clamp in the rats. By analyzing fragment peaks of gas chromatography mass spectrometry (GCMS) of various kinds of ^<13>C-glucose ([1-^<13>C]-,[2-^<13>C]-,[U-^<13>C]-), it was concluded that the derivatization of glucose with N-methyl bis[trifluoroacetamide] is most suitable for the acurate assessment of ^<13>C enrichment in the glucose of plasma samples and therefore for the calculation of glucose turnovers.