Intraportally Delivered Glucose and Glucagon-Like Peptide-1 Determine Distribution of Glucose Uptake.

Autor: Johnson, Kathryn M., Edgerton, Dale S., Rodewald, Tiffany D., Farmer, Ben, Neal, Doss, Scott, Melanie, Smith, Marta, Hajizadeh, Susan, Donahue, Patrick, Poffenberger, Greg, Snead, Wanda, Cherrington, Alan D.
Předmět:
Zdroj: Diabetes; Jun2007 Supplement 1, Vol. 56, pA371-A372, 2p
Abstrakt: In previous experiments conscious dogs received glucose intraportally (4 mg/kg/min) and peripherally to clamp arterial plasma glucose levels at 160 mg/dl in the presence (PoGlu-GLP, n=11) or absence (PoGlu-CON, n=8) of an intraportal infusion of glucagon-like peptide-1 (GLP-1, 1 pmol/kg/min) for 240 minutes. These rates of glucose and GLP-1 infusion created portal vein levels resembling those observed after an oral glucose load. PoGlu-GLP required a significantly (p = 0.03) greater peripheral glucose infusion (GIR) (4.5 ± 0.7 mg/kg/min, over the last 2 hours of the study) than PoGlu-CON (2.1 ± 0.5 mg/kg/min). The greater GIR was accounted for by an increase in non-hepatic glucose uptake. This increase occurred despite there being no difference in arterial plasma insulin (23 ± 3, 24 ± 2 µU/ml) or glucagon levels (30 ± 3, 23 ± 2 pg/ml) between groups. Increased glucose levels within the portal vein decrease afferent vagal firing, while elevated portal vein GLP-1 levels increase afferent vagal firing. To see if portal glucose delivery was essential for the GLP-1 effect, the study was repeated using only a peripheral glucose infusion to clamp the arterial plasma glucose levels at 160 mg/dl again in the presence (PeGlu-GLP, n=6) or absence (PeGlu-CON, n=6) of an intraportal GLP-1 (1 pmol/kg/min) infusion. There was no difference in GIR needed to maintain the glucose clamp in the two groups (6.4±1.3, 6.1±1.1 mg/kg/min). Once again, there was no difference in arterial plasma insulin (28±5, 24±1 µU/ml) or glucagon levels (22±5, 20±6 pg/ml). Taken together our studies indicate that a physiologic increase in intraportal GLP-1 increased non-hepatic glucose uptake but only in the presence of intraportal glucose delivery. Furthermore, this increase was not dependent on changes in pancreatic hormone levels. These data thus suggest that portal vein GLP-1 sensing plays a role in the tissue distribution of an oral glucose load. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index