Insulin inhibition of overnight glucose production and gluconeogenesis from lactate in NIDDM.
Increased gluconeogenesis contributes to fasting hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM). We examined whether insulin inhibits gluconeogenesis from lactate by altering the fate of lactate and/or by reducing lactate flux. Seven patients with NIDDM (age 51 +/- 4 yr, body mass index 28 +/- 2 kg/m2) were studied before and 3 wk after achieving normoglycemia with evening insulin therapy. Basal glucose production (Ra) and utilization were measured overnight [( 3-3H]glucose infusion from 9 P.M. to 8 A.M.) and lactate turnover and conversion to glucose between 4 and 8 A.M. [( U-14C]lactate infusion) before and after insulin therapy. During insulin therapy, fasting plasma glucose decreased from 188 +/- 13 to 99 +/- 7 mg/dl (P less than 0.001) due to inhibition of glucose Ra from 3.0 +/- 0.1 to 2.2 +/- 0.1 mumol.kg-1.min-1 (P less than 0.005). Plasma free insulin increased from 6 +/- 1 to 11 +/- 1 microU/ml (P less than 0.005). Plasma lactate concentrations (1.1 +/- 0.2 vs. 1.0 +/- 0.1 mmol/l before vs. after insulin therapy) and the lactate turnover rate (15.6 +/- 0.9 vs. 14.2 +/- 0.8 mumol.kg.min) remained unchanged, whereas the amount of glucose formed from lactate decreased from 2.0 +/- 0.1 to 1.4 +/- 0.2 mumol.kg-1.min-1 (P less than 0.02) and the percent of lactate turnover converted to glucose decreased from 26 +/- 1 to 20 +/- 2% (P less than 0.05). We conclude that insulin inhibits overnight glucose Ra from lactate by decreasing the proportion of lactate diverted towards gluconeogenesis rather than by altering lactate availability or total flux.
Yki-Järvinen
H
H
Second Department of Medicine, University of Helsinki, Finland.
Helve
E
E
Sane
T
T
Nurjhan
N
N
Taskinen
M R
MR
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D007700:Kinetics; D007773:Lactates / Q000097:blood*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates