Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM

• Published in: Diabetes (New York, N.Y.) Vol. 39; no. 11; pp. 1381 - 1390
• Main Authors: Mitrakou, A., Kelley, D., Veneman, T., Jenssen, T., Pangburn, T., Reilly, J., Gerich, J.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.11.1990
• Subjects: 550501 - Metabolism- Tracer Techniques; 550901 - Pathology- Tracer Techniques; ALANINES; ALDEHYDES; AMINO ACIDS; BASIC BIOLOGICAL SCIENCES; BODY; CARBOHYDRATES; CARBON 14 COMPOUNDS; CARBON COMPOUNDS; CARBON DIOXIDE; CARBON OXIDES; CARBOXYLIC ACID SALTS; CARBOXYLIC ACIDS; CHALCOGENIDES; DIABETES MELLITUS; DIGESTIVE SYSTEM; DISEASES; ELEMENTS; ENDOCRINE DISEASES; GLANDS; GLUCOSE; HEXOSES; HYPERGLYCEMIA; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; LACTATES; LIVER; METABOLIC DISEASES; METABOLISM; MONOSACCHARIDES; MUSCLES; NONMETALS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; OXIDES; OXYGEN; OXYGEN COMPOUNDS; PATHOGENESIS; SACCHARIDES; TRACER TECHNIQUES
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.39.11.1381

Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM. A Mitrakou , D Kelley , T Veneman , T Jenssen , T Pangburn , J Reilly and J Gerich Department of Medicine, University of Pittsburgh School of Medicine, PA. Abstract To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with [14C]glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2 (with forearm calorimetry). In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects (45.1 +/- 2.3 vs. 34.4 +/- 1.5 g, P less than 0.01), but glucose Rd was not significantly different in NIDDM (35.1 +/- 2.4 g) and nondiabetic (33.3 +/- 2.7 g) subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM.