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Fasting Decreases Rates of Noninsulin-Mediated Glucose Uptake in Man^*

ALAIN D. BARON, GINGER BRECHTEL, PENNY WALLACE and STEVEN V. EDELMAN

Department of Medicine, University of California, and the Medical Research Service, Veterans Administration Medical Center San Diego, California 92161

Address all correspondence and requests for reprints to: Alain D. Baron, M.D., Veterans Administration Medical Center (V-111G), 3350 La Jolla Village Drive, San Diego, California 92161.

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 µg/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 < 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 < 0.01 between all values). During insulinopenia plasma FFA and serum betahydroxybutyrate 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 < 0.001). Results in the lean group were similar to those in the obese group after a 3-day fast.

In summary, 1) fasting did not modulate NIMGU during euglycemia; 2) a 9-day fast caused a 20% decrease in NIMGU during hyperglycemia (11 mmol/L) and a 40% fall in NIMGU into non-CNS tissues (NIMGU at 11 mmol/L – NIMGU at 4.7 mmol/L). Thus, fasting does not modulate CNS glucose uptake despite a marked rise in the availability of the brain metabolic substrate β-hydroxybutyrate and fasting decreases the rate of NIMGU in non-CNS tissues.

^* This work was supported in part by Dr. Olefsky's Grants Am-33649 from the NIADDK, NIH and grants from the Medical Research Services of the V.A. Medical Center; Grant RR-00827 from the Clinical Research Center, NIH; and the Juvenile Diabetes Foundation.

Clinical Associate Physician of the General Clinical Research Center, NIH, and recipient of a Juvenile Diabetes Foundation Research grant.

Received December 14, 1987.