title: Effect of exenatide on postprandial glucose fluxes, lipolysis, and ß-cell function in non-diabetic, morbidly obese patients.
abstract: To investigate the effect of exenatide on glucose disposal, insulin secretion, ß-cell function, lipolysis and hormone concentrations in non-diabetic, morbidly obese subjects under physiological conditions.
  
  
  
  Patients were assigned to exenatide 10 µg twice daily (EXE, n = 15) or control (CT, n = 15) for 3 months. Patients received a meal test/tracer study (MTT) to measure endogenous glucose production (EGP), rate of oral glucose appearance (RaO), insulin secretion rate (ISR), ß-cell function, hepatic insulin resistance (HIR) and adipose tissue insulin resistance (AT-IR) and insulin sensitivity (IS).
  
  
  
  Post treatment, the EXE group showed a significant reduction in body weight ( P < .001). The postmeal time-course of glucose, insulin and ISR showed a lower peak between 60 and 180 minutes in phase with a reduction in RaO ( P < .01). After an initial similar suppression, EGP resumed at higher rates between 60 and 180 minutes ( P = .02) in EXE vs CT, while total RaO and EGP were similar throughout the MTT. In EXE, the postmeal glucagon, GLP1 and GIP responses were reduced ( P < .05). Fasting and postprandial lipolysis and ß-cell function were unaltered by active treatment. HIR, AT-IR and IS were all improved after exenatide treatment ( P < .05).
  
  
  
  In morbidly obese non-diabetic subjects, exenatide causes weight loss, decreased postprandial glycaemia and glucagon response without changes in ß-cell function. These effects are consequent upon delayed oral glucose appearance in the circulation. Exenatide treatment is also associated with an improvement in hepatic, adipose tissue and whole-body IS with no influence on postprandial lipolysis.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Stefania
authors.identifier: 0000-0001-9015-7244
authors.initials: S
authors.lastname: Camastra
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Brenno
authors.initials: B
authors.lastname: Astiarraga
authors.affiliation: Institute of Neurosciences, C.N.R., Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Frascerra
authors.affiliation: Institute of Clinical Physiology, C.N.R., Pisa, Italy.
authors.forename: Demetrio
authors.initials: D
authors.lastname: Ciociaro
authors.affiliation: Institute of Neurosciences, C.N.R., Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.affiliation: Institute of Clinical Physiology, C.N.R., Pisa, Italy.
authors.forename: Amalia
authors.identifier: 0000-0003-2594-1651
authors.initials: A
authors.lastname: Gastaldelli
authors.affiliation: Institute of Clinical Physiology, C.N.R., Pisa, Italy.
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D000077270:Exenatide; D005215:Fasting / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000187:drug effects / Q000378:metabolism; D005934:Glucagon / Q000187:drug effects / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D019518:Postprandial Period; D014688:Venoms / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide
keywords: GLP-1 receptor agonist; endogenous glucose production; exenatide; glucagon; glucose metabolism; insulin resistance; insulin secretion; lipolysis