title: Effect of exenatide on splanchnic and peripheral glucose metabolism in type 2 diabetic subjects.
abstract: OBJECTIVE
  Our objective was to examine the mechanisms via which exenatide attenuates postprandial hyperglycemia in type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Seventeen T2DM patients (44 yr; seven females, 10 males; body mass index = 33.6 kg/m(2); glycosylated hemoglobin = 7.9%) received a mixed meal followed for 6 h with double-tracer technique ([1-(14)C]glucose orally; [3-(3)H]glucose i.v.) before and after 2 wk of exenatide. In protocol II (n = 5), but not in protocol I (n = 12), exenatide was given in the morning of the repeat meal. Total and oral glucose appearance rates (RaT and RaO, respectively), endogenous glucose production (EGP), splanchnic glucose uptake (75 g - RaO), and hepatic insulin resistance (basal EGP × fasting plasma insulin) were determined.
  
  
  RESULTS
  After 2 wk of exenatide (protocol I), fasting plasma glucose decreased (from 10.2 to 7.6 mm) and mean postmeal plasma glucose decreased (from 13.2 to 11.3 mm) (P < 0.05); fasting and meal-stimulated plasma insulin and glucagon did not change significantly. After exenatide, basal EGP decreased (from 13.9 to 10.8 μmol/kg · min, P < 0.05), and hepatic insulin resistance declined (both P < 0.05). RaO, gastric emptying (acetaminophen area under the curve), and splanchnic glucose uptake did not change. In protocol II (exenatide given before repeat meal), fasting plasma glucose decreased (from 11.1 to 8.9 mm) and mean postmeal plasma glucose decreased (from 14.2 to 10.1 mm) (P < 0.05); fasting and meal-stimulated plasma insulin and glucagon did not change significantly. After exenatide, basal EGP decreased (from 13.4 to 10.7 μmol/kg · min, P = 0.05). RaT and RaO decreased markedly from 0-180 min after meal ingestion, consistent with exenatide's action to delay gastric emptying.
  
  
  CONCLUSIONS
  Exenatide improves 1) fasting hyperglycemia by reducing basal EGP and 2) postmeal hyperglycemia by reducing the appearance of oral glucose in the systemic circulation.
authors.affiliation: Division of Diabetes, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
authors.forename: E
authors.initials: E
authors.lastname: Cersosimo
authors.forename: A
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: A
authors.initials: A
authors.lastname: Cervera
authors.forename: E
authors.initials: E
authors.lastname: Wajcberg
authors.forename: A
authors.initials: A
authors.lastname: Sriwijilkamol
authors.forename: M
authors.initials: M
authors.lastname: Fernandez
authors.forename: P
authors.initials: P
authors.lastname: Zuo
authors.forename: R
authors.initials: R
authors.lastname: Petz
authors.forename: C
authors.initials: C
authors.lastname: Triplitt
authors.forename: N
authors.initials: N
authors.lastname: Musi
authors.forename: R A
authors.initials: RA
authors.lastname: DeFronzo
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D000077270:Exenatide; D005260:Female; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology*; D019518:Postprandial Period / Q000187:drug effects* / Q000502:physiology; D014688:Venoms / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms