Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM.
Excessive hepatic glucose output is an important factor in the fasting hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM). To determine the relative contributions of gluconeogenesis and glycogenolysis in a quantitative manner, we applied a new isotopic approach, using infusions of [6-3H]glucose and [2-14C]acetate to trace overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis in 14 postabsorptive NIDDM subjects and in 9 nondiabetic volunteers of similar age and weight. Overall hepatic glucose output was increased nearly twofold in the NIDDM subjects (22.7 +/- 1.0 vs. 12.0 +/- 0.6 mumol.kg-1.min-1 in the nondiabetic volunteers, P less than .001); phosphoenolpyruvate gluconeogenesis was increased more than threefold in the NIDDM subjects (12.7 +/- 1.4 vs. 3.6 +/- 0.4 mumol.kg-1.min-1 in the nondiabetic subjects, P less than .001) and was accompanied by increased plasma lactate, alanine, and glucagon concentrations (all P less than .05). The increased phosphoenolpyruvate gluconeogenesis accounted for 89 +/- 6% of the increase in overall hepatic glucose output in the NIDDM subjects and was significantly correlated with the fasting plasma glucose concentrations (r = .67, P less than .01). Glycogenolysis, calculated as the difference between overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis, was not significantly different in the NIDDM subjects (9.9 +/- 0.06 mumol.kg-1.min-1) and the nondiabetic volunteers (8.4 +/- 0.3 mumol.kg-1.min-1). We conclude that increased gluconeogenesis is the predominant mechanism responsible for increased hepatic glucose output in NIDDM.
Consoli
A
A
Department of Medicine, University of Pittsburgh, School of Medicine, Pennsylvania.
Nurjhan
N
N
Capani
F
F
Gerich
J
J
D000328:Adult; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002952:Citric Acid Cycle; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D005934:Glucagon; D005947:Glucose; D000409:Alanine