No reduction in total hepatic glucose output by inhibition of gluconeogenesis with ethanol in NIDDM patients.
Increased gluconeogenesis has been suggested to account for all of the increase in basal glucose production in patients with non-insulin-dependent diabetes mellitus (NIDDM). We studied the effect of inhibition of gluconeogenesis with ethanol on total hepatic glucose output (HGO) in patients with NIDDM. Fourteen patients with NIDDM (mean +/- SE age 61 +/- 2 yr, fasting plasma glucose 11.4 +/- 0.8 mM; body mass index 27 +/- 1 kg/m2) were studied twice after an overnight fast, once during ethanol administration (blood ethanol approximately 12 mM) and once during saline administration. Total HGO rate was measured with [3H]glucose. Inhibition of gluconeogenesis by ethanol was followed qualitatively with [U-14C]lactate (n = 8) and [U-14C]glycerol (n = 6) as tracers. Ethanol inhibited gluconeogenesis from lactate by 71 +/- 5% (0.5 +/- 0.2 vs. 1.8 +/- 0.1 mumol glucose.kg-1.min-1, 240-300 min, P less than 0.001; ethanol vs. saline, P less than 0.001) and from glycerol by 65 +/- 6% (0.8 +/- 0.2 vs. 2.3 +/- 0.6 mumol glucose.kg.min-1, P less than 0.001). Total HGO rate remained unchanged and averaged 12.8 +/- 1.8 and 11.8 +/- 2.1 mumol.kg-1.min-1 in the saline and ethanol studies, respectively (NS). We concluded that inhibition of gluconeogenesis by ethanol does not decrease total HGO in patients with NIDDM. Our results suggest the existence of a regulatory mechanism in the liver that maintains constant total HGO despite inhibition of gluconeogenesis.
Second Department of Medicine, University of Helsinki, Finland.
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Puhakainen
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Koivisto
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Yki-Järvinen
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects*; D005990:Glycerol / Q000097:blood; D006801:Humans; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D019344:Lactic Acid; D000431:Ethanol; D005990:Glycerol