Incretin effect potentiates beta-cell responsivity to glucose as well as to its rate of change: OGTT and matched intravenous study.
The aim of this study is to gain greater insight into the mechanism whereby "incretins" (greater insulinemia after oral than intravenous glucose) enhance insulin secretion. To do so, we use a model of C-peptide secretion to reanalyze data from a previously published study in which glycemic profiles observed following glucose ingestion were matched in the same 10 subjects by means of an intravenous glucose infusion. We report that incretins increase insulin secretion by enhancing both the dynamic (to the rate of increase of glucose) and static (to given glucose concentration) response with an increase of 58% for the static (Phi(s) = 16.4 +/- 1.8 vs. 24.6 +/- 2.0 10(-9) min(-1), P = 0.01) and 63% for the dynamic (Phi(d) = 278 +/- 32 vs. 463 +/- 86 10(-9), P = 0.02) indexes. Since increases in the dynamic response to glucose are believed to be due to an increase in the rate of docking, and exocytosis of insulin containing granules and increases in the static response to glucose are believed to be caused by a shift in the sensitivity of the beta-cell to glucose, these results suggest that incretins may modulate more than one step in the beta-cell insulin secretory cascade.
Campioni
Marco
M
Dept. of Information Engineering, Via Gradenigo 6a, 35131 Padua, Italy. cobelli@dei.unipd.it
Toffolo
Gianna
G
Shuster
Lynne T
LT
Service
F John
FJ
Rizza
Robert A
RA
Cobelli
Claudio
C
D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D005951:Glucose Tolerance Test; D006801:Humans; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005947:Glucose