title: Hepatic glucose sensing is impaired, but can be normalized, in people with impaired fasting glucose.
abstract: OBJECTIVE
  Abnormal endogenous glucose production (EGP) is a characteristic feature in people with impaired fasting glucose (IFG). We sought to determine whether impaired hepatic glucose sensing contributes to abnormal EGP in IFG and whether it could be experimentally restored.
  
  
  METHODS
  Glucose production (rate of appearance; Ra) and flux (glucose cycling) were assessed during a hyperglycemic-euinsulinemic somatostatin clamp with an infusion of [6,6-(2)H2-]glucose and [2-(2)H]glucose before and after enhanced hepatic glucokinase activity via an infusion of low-dose fructose in people with IFG and normal glucose tolerance (NGT).
  
  
  RESULTS
  During euglycemia, neither endogenous glucose production [(6,6-(2)H2)-glucose Ra; P = 0.53] or total glucose output (TGO; [2-(2)H]-glucose Ra; P = .12) was different between groups, but glucose cycling ([2-(2)H]glucose Ra to [6,6-(2)H2-]glucose Ra; a surrogate measure of hepatic glucokinase activity in the postabsorptive state) was lower in IFG than NGT (P = .04). Hyperglycemia suppressed EGP more in NGT than IFG (P < .01 for absolute or relative suppression, NGT vs IFG), whereas TGO decreased similarly in both groups (P = .77). The addition of fructose completely suppressed EGP in IFG (P < .01) and tended to do the same to TGO (P = .01; no such changes in NGT, P = .39-.55). Glucose cycling (which reflects glucose-6-phosphatase activity during glucose infusion) was similar in IFG and NGT (P = .51) during hyperglycemia and was unchanged and comparable between groups with the addition of fructose (P = .24).
  
  
  CONCLUSIONS
  In summary, glucose sensing is impaired in IFG but can be experimentally restored with low-dose fructose. Glucokinase activation may prove to be a novel strategy for the prevention of diabetes in this high-risk group.
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes (L.P., A.A.K., S.D.B., B.C.B.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045; and Steno Diabetes Center (K.F.), DK-2820 Gentofte, Denmark.
authors.forename: Leigh
authors.initials: L
authors.lastname: Perreault
authors.forename: Kristine
authors.initials: K
authors.lastname: Færch
authors.forename: Anna A
authors.initials: AA
authors.lastname: Kerege
authors.forename: Samantha D
authors.initials: SD
authors.lastname: Bacon
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Bergman
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005215:Fasting / Q000378:metabolism*; D005260:Female; D005632:Fructose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D011236:Prediabetic State / Q000378:metabolism*; D013004:Somatostatin / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D005632:Fructose; D013004:Somatostatin
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