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)

Meera Shah, Marcello C. Laurenti, Chiara Dalla Man, Jing Ma, Claudio Cobelli, Robert A. Rizza, Adrian Vella

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)10-17
Number of pages8
JournalMetabolism: Clinical and Experimental
Volume93
DOIs
StatePublished - Apr 1 2019
Externally publishedYes

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Glucagon-Like Peptide 1
Gastric Bypass
Type 2 Diabetes Mellitus
Glucose
Insulin
Meals
Obesity
exendin (9-39)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

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). / Shah, Meera; Laurenti, Marcello C.; Dalla Man, Chiara; Ma, Jing; Cobelli, Claudio; Rizza, Robert A.; Vella, Adrian.

In: Metabolism: Clinical and Experimental, Vol. 93, 01.04.2019, p. 10-17.

Research output: Contribution to journalArticle

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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.",
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AU - Rizza, Robert A.

AU - Vella, Adrian

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