title: Mechanisms for abnormal postprandial glucose metabolism in type 2 diabetes.
abstract: To assess mechanisms for postprandial hyperglycemia, we used a triple-isotope technique ([\3-(3)H]glucose and [(14)C]bicarbonate and oral [6,6-dideutero]glucose iv) and indirect calorimetry to compare components of glucose release and pathways for glucose disposal in 26 subjects with type 2 diabetes and 15 age-, weight-, and sex-matched normal volunteers after a standard meal. The results were as follows: 1) diabetic subjects had greater postprandial glucose release (P<0.001) because of both increased endogenous and meal-glucose release; 2) the greater endogenous glucose release (P<0.001) was due to increased gluconeogenesis (P<0.001) and glycogenolysis (P=0.01); 3) overall tissue glucose uptake, glycolysis, and storage were comparable in both groups (P>0.3); 4) glucose clearance (P<0.001) and oxidation (P=0.004) were reduced, whereas nonoxidative glycolysis was increased (P=0.04); and 5) net splanchnic glucose storage was reduced by approximately 45% (P=0.008) because of increased glycogen cycling (P=0.03). Thus in type 2 diabetes, postprandial hyperglycemia is primarily due to increased glucose release; hyperglycemia overcomes the effects of impaired insulin secretion and sensitivity on glucose transport, but intracellular defects persist so that pathways of glucose metabolism are abnormal and glucose is shunted away from normal sites of storage (e.g., liver and muscle) into other tissues.
authors.affiliation: Department of Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
authors.forename: Ervin
authors.initials: E
authors.lastname: Szoke
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.forename: Jean M
authors.initials: JM
authors.lastname: Dostou
authors.forename: Steven D
authors.initials: SD
authors.lastname: Wittlin
authors.forename: Niyaz R
authors.initials: NR
authors.lastname: Gosmanov
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Welle
authors.forename: John E
authors.initials: JE
authors.lastname: Gerich
mesh_terms: D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000097:blood; D050261:Glycogenolysis / Q000502:physiology; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D019518:Postprandial Period / Q000502:physiology*; D014781:Viscera / Q000378:metabolism; D014867:Water / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014867:Water; D002245:Carbon Dioxide; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose; D000409:Alanine; D005990:Glycerol