Fasting decreases rates of noninsulin-mediated glucose uptake in man

Abstract

Although fasting decreases insulin-mediated glucose uptake (IMGU), its effect on noninsulin-mediated glucose uptake (NIMGU) is not known. To examine this issue we studied seven obese men [mean (+/- SD) age, 36 +/- 5 yr; weight, 91 +/- 13 kg] after an overnight fast (day 0) and 3 days (day 4) and 9 days (day 10) of total fasting and six normal weight men (age, 32 +/- 4 yr; weight, 73 +/- 6 kg) after an overnight and 3 days of fasting. To study NIMGU, somatostatin (0.16 micrograms/kg.min) was infused to create severe insulin deficiency and [3H]3-glucose to measure glucose disappearance (Rd), while serum glucose was sequentially clamped at a level of about 4.7 mmol/L for 180 min and about 11 mmol/L for an additional 100 min. The results from the last 60 min of each glycemic plateau were used for analysis. Under these conditions insulin action is absent and Rd = NIMGU. Since under conditions of euglycemic insulinopenia, NIMGU into noncentral nervous system tissues is negligible, and central nervous system (CNS) glucose uptake saturates at physiological glucose concentrations, it follows that at a glucose level of about 4.7 mmol/L, NIMGU reflects CNS glucose uptake and at about 11 mmol/L, NIMGU reflect CNS plus non-CNS tissues. Thus, non-CNS NIMGU = NIMGU at 11 mmol/L - NIMGU at about 4.7 mmol/L. The obese subjects' mean weight fell to 88 +/- 5 kg on day 4 and 85 +/- 5 kg on day 10 (P less than 0.001 between all values). The mean basal serum glucose level fell from 5.3 +/- 0.1 on day 0 to 4.2 +/- 0.2 and 3.8 +/- 0.2 mmol/L on days 4 and 10, respectively (P less than 0.01 between all values). During insulinopenia plasma FFA and serum beta-hydroxybutyrate levels on day 10 were 3- and 30-fold higher than the basal prefast levels, respectively. Noninsulin-mediated glucose clearance at about 4.7 mmol/L did not change during fasting [0.0016 +/- 0.0001 (day 0) vs. 0.0016 +/- 0.0001 (day 4) and 0.0014 +/- 0.0001 L/kg.min (day 10); P = NS between all values]; at about 11 mmol/L noninsulin-mediated glucose clearance fell from 0.0016 +/- 0.0001 on day 0 to 0.0001 +/- 0.0001 dL/kg.min on day 10 (P less than 0.001). Results in the lean group were similar to those in the obese group after a 3-day fast.(ABSTRACT TRUNCATED AT 400 WORDS)