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- Title
Glucagon-like peptide 1 increases insulin sensitivity in depancreatized dogs.
- Authors
Sandhu, Harmanjit; Wiesenthal, Stephanie R.; MacDonald, Patrick E.; McCall, Richard H.; Tchipashvili, Vaja; Rashid, Shirya; Satkunarajah, Malathy; Irwin, David M.; Z. Qing Shi; Brubaker, Patricia L.; Wheeler, Michael B.; Vranic, Mladen; Efendic, Suad; Giacca, Adria; Sandhu, H; Wiesenthal, S R; MacDonald, P E; McCall, R H; Tchipashvili, V; Rashid, S
- Abstract
To determine whether glucagon-like peptide (GLP)-1 increases insulin sensitivity in addition to stimulating insulin secretion, we studied totally depancreatized dogs to eliminate GLP-1's incretin effect. Somatostatin was infused (0.8 microg x kg(-1) x min(-1)) to inhibit extrapancreatic glucagon in dogs, and basal glucagon was restored by intraportal infusion (0.65 ng x kg(-1) x min(-1)). To simulate the residual intraportal insulin secretion in type 2 diabetes, basal intraportal insulin infusion was given to obtain plasma glucose concentrations of approximately 10 mmol/l. Glucose was clamped at this level for the remainder of the experiment, which included peripheral insulin infusion (high dose, 5.4 pmol x kg(-1) x min(-1), or low dose, 0.75 pmol x kg(-1) x min(-1)) with or without GLP-1(7-36) amide (1.5 pmol x kg(-1) x min(-1)). Glucose production and utilization were measured with 3-[3H]glucose, using radiolabeled glucose infusates. In 12 paired experiments with six dogs at the high insulin dose, GLP-1 infusion resulted in higher glucose requirements than saline (60.9+/-11.0 vs. 43.6+/-8.3 micromol x kg(-1) x min(-1), P< 0.001), because of greater glucose utilization (72.6+/-11.0 vs. 56.8+/-9.7 micromol x kg(-1) x min(-1), P<0.001), whereas the suppression of glucose production was not affected by GLP-1. Free fatty acids (FFAs) were significantly lower with GLP-1 than saline (375.3+/-103.0 vs. 524.4+/-101.1 micromol/l, P<0.01), as was glycerol (77.9+/-17.5 vs. 125.6+/-51.8 micromol/l, P<0.05). GLP-1 receptor gene expression was found using reverse transcriptase-polymerase chain reaction of poly(A)-selected RNA in muscle and adipose tissue, but not in liver. Low levels of GLP-1 receptor gene expression were also found in adipose tissue using Northern blotting. In 10 paired experiments with five dogs at the low insulin dose, GLP-1 infusion did not affect glucose utilization or FFA and glycerol suppression when compared with saline, suggesting that GLP-1's effect on insulin action was dependent on the insulin dose. In conclusion, in depancreatized dogs, GLP-1 potentiates insulin-stimulated glucose utilization, an effect that might be contributed in part by GLP-1 potentiation of insulin's antilipolytic action.
- Subjects
GLUCAGON-like peptide 1; PHYSIOLOGICAL transport of insulin; GLUCOSE
- Publication
Diabetes, 1999, Vol 48, Issue 5, p1045
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.48.5.1045