Excessive hepatic glucose output is an important factor in the fasting hyperglycemia of non-insulindependent 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 μmol · kg−1 · min−1 in the nondiabetic volunteers, P < .001); phosphoenolpyruvate gluconeogenesis was increased more than threefold in the NIDDM subjects (12.7 ± 1.4 vs. 3.6 ± 0.4 μmol kg−1 min−1 in the nondiabetic subjects, P < .001) and was accompanied by increased plasma lactate, alanine, and glucagon concentrations (all P < .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 < .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 μmol · kg−1 · min−1) and the nondiabetic volunteers (8.4 ± 0.3 μmol kg−1 · min−1). We conclude that increased gluconeogenesis is the predominant mechanism responsible for increased hepatic glucose output in NIDDM.
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Original Articles| May 01 1989
Predominant Role of Gluconeogenesis in Increased Hepatic Glucose Production in NIDDM
Address correspondence and reprint requests to John E. Gerich, MD, Clinical Research Center, 3488 Presbyterian-University Hospital, 230 Lothrop Street, Pittsburgh, PA 15261.
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Agostino Consoli, Nurjahan Nurjhan, Fabio Capani, John Gerich; Predominant Role of Gluconeogenesis in Increased Hepatic Glucose Production in NIDDM. Diabetes 1 May 1989; 38 (5): 550–557. https://doi.org/10.2337/diab.38.5.550
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