title: Effect of acute hyperglycemia on insulin secretion in humans.
abstract: First-phase insulin response to intravenous glucose is impaired both in type 2 diabetic patients and in subjects at risk for the disease. Hyperglycemia can modify beta-cell response by either inhibiting or potentiating both first- and second-phase insulin release. In normal subjects, the effect of acute hyperglycemia on insulin secretion is controversial. We measured (in 13 healthy volunteers) insulin secretion (by deconvolution of plasma C-peptide concentrations) during three consecutive 30-min hyperglycemic steps (2.8, 2.8, and 5.6 mmol/l), followed by an intravenous arginine bolus. First-phase insulin secretion in response to the first hyperglycemic step (456 +/- 83 pmol.min(-1).m(-2)) was significantly larger than that in response to the second step (311 +/- 37 pmol.min(-1).m(-2), P < 0.01); the subsequent increase in glycemia failed to stimulate first-phase secretion any further (377 +/- 60 pmol.min(-1).m(-2), NS vs. the previous value). This inhibition was also evident when insulin release rates were corrected for the respective increments (absolute or percentage) in plasma glucose levels and was not due to beta-cell exhaustion because the arginine bolus still elicited a large peak of insulin secretion (4,790 +/- 2,330 pmol.min(-1).m(-2)). In contrast, second-phase insulin secretion was related to the prevailing glucose levels across the three hyperglycemic steps in a direct quasilinear manner. We conclude that first-phase insulin secretion is inhibited by short-term modest hyperglycemia, whereas the second-phase insulin secretion increases linearly with hyperglycemia.
authors.affiliation: Metabolism Unit, CNR Institute of Clinical Physiology, University of Pisa, Via Savi 8, 56126 Pisa, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Toschi
authors.forename: Stefania
authors.initials: S
authors.lastname: Camastra
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sironi
authors.forename: Antonio
authors.initials: A
authors.lastname: Masoni
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Andrea
authors.initials: A
authors.lastname: Natali
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001120:Arginine / Q000008:administration & dosage; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D002096:C-Peptide; D007328:Insulin; D001120:Arginine; D005947:Glucose