J Korean Diabetes Assoc.
1998 Mar;22(1):47-55.
The Effect of Elevated Plasma Free Fatty Acids on Non-Insulin-Mediated Glucose Uptake and Insulin
Resistance
Abstract
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BACKGROUND: In vivo glucose uptake occurs via two mechanisms, namely insulin-mediated glucose uptake(IMGU) and
non-insulin-mediated glucose up-take(NIMGU). NIMGU accaunts for about 70~85% of postabsorptive glucose uptake.
Despite many studies, it is still controversial how an increase in lipolysis affects glucose metabolism in man. More
specifically, the effect of free fatty acid(FFA) on NIMGU has not been exanuned. METHOD: Two-step(euglycemia-
hyperglycemia) glucose clamp techique with [3-H]-glucose infusion was performed in 6 normal men. Each man
was studied twice, with(test experiement) and without (control experiment) the administration of lipid and heparin at
an interval of at least 4 weeks in random order. The subjects received an insulin infusion at 1.1 pmol/kg. min in
conjuction with the infusion of somatostatin(step 1, 153 nmol/h; step 2, 458 nmol/h). Result: Plasma glucose levels
during step 1 were 5.4+0.1 mmol/L(control experiment), 5.4+0.1 mmol/ L(test experiment), and were raised to 14.7+0.2
mmol/L, 14.6+0.1 mmol/L, respectively, during step 2. Plasma insulin levels during step 1 were 56+4 pmol/L(control
experiment), 52+4 pmol/L(test experiment), and were 65+3 pmol/L, 62+4 pmol/L, respectively, during step 2. In control
experiment, plasma FFA levels were 0.24+0.02 mmol/L during step 1 and 0.11+0.01 mmol/L during step 2. In test
experiment, plasma FFA levels increased significantly to 1.08+0.06 mmol/L during step 1 and 1.01 +0.04 mmol/L
during step 2, respectively(p<0.01). Glucose infusion rate(GIR) to increase glucose concentrations to the desired
levels were 7.7+0.8 pnol/ kg,min during step 1 and 29.7+3.7 pmol/kg.min during step 2 in control experiment. In test
experiment, GIR decreawd significantly to 3.8+0.9 pmol/ kg.min during step 1 and 20.7+1.2 pmol/kg.min during step 2,
respectively(p<0.05). There was no significant difference between NIMGU, estimated by the difference between glucose
disapperance rate of step 1 and step 2 of lipid infusion test experiment and that of control experiment. CONCLUSION: These
results
showed that artificial elevation of plasma FFA levels led to a state of insulin resistance, however, the change of FFA level did not influence NIMGU in man.