Effects of glucose ingestion versus infusion on pulsatile insulin secretion. The incretin effect is achieved by amplification of insulin secretory burst mass.
In the present studies, we used a recently validated canine model to determine 1) if glucose ingestion stimulates insulin secretion by amplifying the pulsatile component of insulin release, and if so, 2) whether this effect is achieved preferentially through burst mass or frequency modulation, and 3) if the mechanism of incretin effect of insulin secretion is mediated via the pulsatile mode of secretion. We report that 30 g of glucose ingestion stimulates an approximately 550% increase in the overall rate of insulin secretion (1.8 +/- 0.2 to 11.6 +/- 1.5 pmol.kg-1.min-1), which is achieved via an approximately 400% increase in the mass of insulin secreted per burst (202 +/- 38 to 1,003 +/- 147 pmol/pulse, P < 0.001) and a approximately 40% increase in burst frequency (8.7 +/- 0.5 to 12.3 +/- 0.6 pulse/h, P < 0.001). Of the insulin secreted after glucose ingestion, 68% (+/-4) was released in discrete secretory bursts. Further analyses showed that the incretin effect of ingested (GPO) versus infused glucose (GIV) is achieved through regulation of pulsatile insulin secretion. Glucose ingestion led to an approximately 70% greater rate of insulin secretion than intravenous glucose delivery (10.0 +/- 1.6 vs. 5.9 +/- 0.9 pmol.kg-1.min-1, P < 0.005, GPO vs. GIV). This incretin effect was achieved by the specific mechanism of an approximately 70% greater pulse mass (930 +/- 196 vs. 558 +/- 97 pmol/pulse, P < 0.02, GPO vs. GIV) but with a comparable pulse frequency (13.1 +/- 0.9 vs. 12.0 +/- 0.5 pulses/h, P = 0.14, n = 9 dogs, GPO vs. GIV). We conclude that in vivo glucose regulates overall insulin secretion almost exclusively by amplification of the pulsatile mode of insulin secretion, and that the incretin effect is achieved by preferential enhancement of insulin secretory burst mass.
Pørksen
N
N
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA.
Munn
S
S
Steers
J
J
Veldhuis
J D
JD
Butler
P C
PC
D000818:Animals; D004040:Dietary Carbohydrates; D004285:Dogs; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D011169:Portal Vein; D019518:Postprandial Period; D013997:Time Factors
D004040:Dietary Carbohydrates; D007328:Insulin; D005947:Glucose