Regulation of islet hormone release and gastric emptying by endogenous glucagon-like peptide 1 after glucose ingestion

Marzieh Salehi, Torsten P. Vahl, David A. D'Alessio

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Background: Exogenous administration of glucagon-like peptide (GLP)-1 improves glucose tolerance by stimulation of insulin secretion, inhibition of glucagon secretion, and delay of gastric emptying. It is not known which of these effects is involved in the action of endogenous GLP-1 to control blood glucose. To determine the role of endogenous GLP-1 on islet cell function and gastric emptying independent of variable glycemia, we clamped blood glucose before and during glucose ingestion with and without GLP-1 receptor blockade with exendin-[9-39] (Ex-9). Methods: There were 10 healthy subjects that participated in two experiments each, one a control and one with infusion of 750 pm/kg·min Ex-9. Subjects consumed 75 g oral glucose solution mixed with D-xylose and 13C-glucose while their blood glucose levels were held fixed at approximately 8.9 mmol/liter. Results: Plasma insulin levels during hyperglycemia alone were similar in the two studies (control, 282.5 ± 42 vs. Ex-9, 263.8 ± 59 pmol/liter) but were reduced by approximately 30% by Ex-9 after glucose ingestion (control, 1154± 203 vs. Ex-9, 835± 120 pmol/liter; P < 0.05). Blocking the action of endogenous GLP-1 caused an approximate 80% increase in postprandial glucagon concentrations. The appearance of ingested D-xylose in the blood was not affected by Ex-9, suggesting that postprandial secretion of GLP-1 has only minimal effects on gastric emptying of oral glucose. Conclusions: These findings indicate that GLP-1 is an incretin in healthy humans at modestly supraphysiological blood glucose levels. The primary effect of GLP-1 to regulate oral glucose tolerance is mediated by effectsonislet hormones and notongastric emptying.

Original languageEnglish (US)
Pages (from-to)4909-4916
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number12
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

Glucagon-Like Peptide 1
Gastric Emptying
Eating
Hormones
Glucose
Blood Glucose
Xylose
Glucagon
Insulin
Incretins
Glucose Tolerance Test
Islets of Langerhans
Hyperglycemia
exendin (9-39)
Healthy Volunteers
Blood
Plasmas

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Regulation of islet hormone release and gastric emptying by endogenous glucagon-like peptide 1 after glucose ingestion. / Salehi, Marzieh; Vahl, Torsten P.; D'Alessio, David A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 93, No. 12, 01.01.2008, p. 4909-4916.

Research output: Contribution to journalArticle

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abstract = "Background: Exogenous administration of glucagon-like peptide (GLP)-1 improves glucose tolerance by stimulation of insulin secretion, inhibition of glucagon secretion, and delay of gastric emptying. It is not known which of these effects is involved in the action of endogenous GLP-1 to control blood glucose. To determine the role of endogenous GLP-1 on islet cell function and gastric emptying independent of variable glycemia, we clamped blood glucose before and during glucose ingestion with and without GLP-1 receptor blockade with exendin-[9-39] (Ex-9). Methods: There were 10 healthy subjects that participated in two experiments each, one a control and one with infusion of 750 pm/kg·min Ex-9. Subjects consumed 75 g oral glucose solution mixed with D-xylose and 13C-glucose while their blood glucose levels were held fixed at approximately 8.9 mmol/liter. Results: Plasma insulin levels during hyperglycemia alone were similar in the two studies (control, 282.5 ± 42 vs. Ex-9, 263.8 ± 59 pmol/liter) but were reduced by approximately 30{\%} by Ex-9 after glucose ingestion (control, 1154± 203 vs. Ex-9, 835± 120 pmol/liter; P < 0.05). Blocking the action of endogenous GLP-1 caused an approximate 80{\%} increase in postprandial glucagon concentrations. The appearance of ingested D-xylose in the blood was not affected by Ex-9, suggesting that postprandial secretion of GLP-1 has only minimal effects on gastric emptying of oral glucose. Conclusions: These findings indicate that GLP-1 is an incretin in healthy humans at modestly supraphysiological blood glucose levels. The primary effect of GLP-1 to regulate oral glucose tolerance is mediated by effectsonislet hormones and notongastric emptying.",
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