title: Metabolic fate of plasma glucose during hyperglycemia in impaired glucose tolerance: evidence for further early defects in the pathogenesis of type 2 diabetes.
abstract: We examined the intracellular metabolic fate of plasma glucose during a hyperglycemic clamp in impaired glucose-tolerant (IGT; n = 21) and normal glucose-tolerant subjects (n = 10) using a combination of [3-(3)H]glucose infusion with measurement of [(3)H]water formation and indirect calorimetry. IGT was associated with approximately 35% reduced first-phase insulin responses, normal second-phase insulin response, and 25-30% reduced insulin sensitivity, resulting in approximately 35% reduced plasma glucose disposal. This was coupled with approximately 55% reduced storage of plasma glucose (P < 0.01) and approximately 15-20% reduced glycolysis of plasma glucose (P < 0.03), accounting for approximately 75 and 25% of the reduction in glucose disposal, respectively. Decreased glucose oxidation accounted for virtually all the decrease in glycolysis. Therefore, nonoxidative glycolysis of plasma glucose in IGT was similar to that in NGT (P > 0.9) and accounted for an increased proportion of systemic glucose disposal (P < 0.05). We conclude that, in IGT, decreased disposal of plasma glucose involves mainly decreased glycogen synthesis and to a lesser extent decreased glycolysis, which is accounted for by decreased glucose oxidation. An increased proportion of plasma glucose hence undergoes nonoxidative glycolysis, representing a novel early abnormality in the pathogenesis of T2DM.
authors.affiliation: Department of Endocrinology, Carl T. Hayden VA Medical Center, Phoenix, AZ 85012, USA.
authors.forename: Syed
authors.initials: S
authors.lastname: Bokhari
authors.forename: Peter
authors.initials: P
authors.lastname: Emerson
authors.forename: Zarmen
authors.initials: Z
authors.lastname: Israelian
authors.forename: Anchal
authors.initials: A
authors.lastname: Gupta
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
mesh_terms: D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D019344:Lactic Acid; D006003:Glycogen; D005934:Glucagon; D000409:Alanine