Contribution of endogenous glucagon-like peptide-1 to changes in glucose metabolism and islet function in people with type 2 diabetes four weeks after Roux-en-Y gastric bypass (RYGB)

Abstract

Glucagon-Like Peptide-1 (GLP-1) is an insulin secretagogue which is elevated after Roux-en-Y Gastric Bypass (RYGB). However, its contribution to glucose metabolism after RYGB remains uncertain.

Aims: We tested the hypothesis that GLP-1 lowers postprandial glucose concentrations and improves β-cell function after RYGB.

Materials and methods: To address these questions we used a labeled mixed meal to assess glucose metabolism and islet function in 12 obese subjects with type 2 diabetes studied before and four weeks after RYGB. During the post-RYGB study subjects were randomly assigned to receive an infusion of either saline or Exendin-9,39 a competitive antagonist of GLP-1 at its receptor. Exendin-9,39 was infused at 300 pmol/kg/min for 6 h. All subjects underwent RYGB for medically-complicated obesity.

Results: Exendin-9,39 resulted in increased integrated incremental postprandial glucose concentrations (181 ± 154 vs. 582 ± 129 mmol per 6 h, p = 0.02). In contrast, this was unchanged in the presence of saline (275 ± 88 vs. 315 ± 66 mmol per 6 h, p = 0.56) after RYGB. Exendin-9,39 also impaired β-cell responsivity to glucose but did not alter Disposition Index (DI).

Conclusions: These data indicate that the elevated GLP-1 concentrations that occur early after RYGB improve postprandial glucose tolerance by enhancing postprandial insulin secretion.

Figure 1:

Total GLP-1 concentrations in the Saline → Exendin-9,39 (left panels) and the Saline → Saline (right panels) group pre-RYGB + Saline (○) and post-RYGB + Exendin-9,39 (●) or post-RYGB + Saline (◆).

Figure 2:

Glucose, Insulin, C-peptide and glucagon concentrations in the Saline → Exendin-9,39 (left panels) and the Saline → Saline (right panels) group pre-RYGB + Saline (○) and post-RYGB + Exendin-9,39 (●) or post-RYGB + Saline (◆).

Figure 3:

Insulin action (S_i), dynamic (φ_d). static (φ_s,) and total (Φ) β-cell responsivity to glucose as well as Disposition Index, in the Saline → Exendin-9,39 group and the Saline → Saline group pre-RYGB + Saline (○) and post-RYGB + Exendin-9,39 (●) or post-RYGB + Saline (◆). The third column shows Symmetrical percent change for each study arm. * denotes p < 0.05.

Figure 4:

Glucagon-Like Peptide-1-induced potentiation of post-prandial insulin secretion (π) in the presence of Saline (open bars) and Exendin-9,39 (solid bars). * denotes p < 0.05.

Figure 5:

Endogenous glucose production, rate of systemic meal appearance and glucose disappearance in the Saline → Exendin-9,39 and the Saline → Saline group pre-RYGB + Saline (○) and post-RYGB + Exendin-9,39 (●) or post-RYGB + Saline (◆).