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The separate and combined impact of the intestinal hormones, GIP, GLP-1, and GLP-2, on glucagon secretion in type 2 diabetes.
Am J Physiol Endocrinol Metab. 2011 Jun; 300(6):E1038-46.AJ

Abstract

Type 2 diabetes mellitus (T2DM) is associated with reduced suppression of glucagon during oral glucose tolerance test (OGTT), whereas isoglycemic intravenous glucose infusion (IIGI) results in normal glucagon suppression in these patients. We examined the role of the intestinal hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2) in this discrepancy. Glucagon responses were measured during a 3-h 50-g OGTT (day A) and an IIGI (day B) in 10 patients with T2DM [age (mean ± SE), 51 ± 3 yr; body mass index, 33 ± 2 kg/m(2); HbA(1c), 6.5 ± 0.2%]. During four additional IIGIs, GIP (day C), GLP-1 (day D), GLP-2 (day E) and a combination of the three (day F) were infused intravenously. Isoglycemia during all six study days was obtained. As expected, no suppression of glucagon occurred during the initial phase of the OGTT, whereas significantly (P < 0.05) lower plasma levels of glucagon during the first 30 min of the IIGI (day B) were observed. The glucagon response during the IIGI + GIP + GLP-1 + GLP-2 infusion (day F) equaled the inappropriate glucagon response to OGTT (P = not significant). The separate GIP infusion (day C) elicited significant hypersecretion of glucagon, whereas GLP-1 infusion (day D) resulted in enhancement of glucagon suppression during IIGI. IIGI + GLP-2 infusion (day E) resulted in a glucagon response in the midrange between the glucagon responses to OGTT and IIGI. Our results indicate that the intestinal hormones, GIP, GLP-1, and GLP-2, may play a role in the inappropriate glucagon response to orally ingested glucose in T2DM with, especially, GIP, acting to increase glucagon secretion.

Authors+Show Affiliations

Diabetes Research Division, Department of Internal Medicine F, Gentofte Hospital, Hellerup, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21386059

Citation

Lund, Asger, et al. "The Separate and Combined Impact of the Intestinal Hormones, GIP, GLP-1, and GLP-2, On Glucagon Secretion in Type 2 Diabetes." American Journal of Physiology. Endocrinology and Metabolism, vol. 300, no. 6, 2011, pp. E1038-46.
Lund A, Vilsbøll T, Bagger JI, et al. The separate and combined impact of the intestinal hormones, GIP, GLP-1, and GLP-2, on glucagon secretion in type 2 diabetes. Am J Physiol Endocrinol Metab. 2011;300(6):E1038-46.
Lund, A., Vilsbøll, T., Bagger, J. I., Holst, J. J., & Knop, F. K. (2011). The separate and combined impact of the intestinal hormones, GIP, GLP-1, and GLP-2, on glucagon secretion in type 2 diabetes. American Journal of Physiology. Endocrinology and Metabolism, 300(6), E1038-46. https://doi.org/10.1152/ajpendo.00665.2010
Lund A, et al. The Separate and Combined Impact of the Intestinal Hormones, GIP, GLP-1, and GLP-2, On Glucagon Secretion in Type 2 Diabetes. Am J Physiol Endocrinol Metab. 2011;300(6):E1038-46. PubMed PMID: 21386059.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The separate and combined impact of the intestinal hormones, GIP, GLP-1, and GLP-2, on glucagon secretion in type 2 diabetes. AU - Lund,Asger, AU - Vilsbøll,Tina, AU - Bagger,Jonatan I, AU - Holst,Jens J, AU - Knop,Filip K, Y1 - 2011/03/08/ PY - 2011/3/10/entrez PY - 2011/3/10/pubmed PY - 2011/7/30/medline SP - E1038 EP - 46 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 300 IS - 6 N2 - Type 2 diabetes mellitus (T2DM) is associated with reduced suppression of glucagon during oral glucose tolerance test (OGTT), whereas isoglycemic intravenous glucose infusion (IIGI) results in normal glucagon suppression in these patients. We examined the role of the intestinal hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2) in this discrepancy. Glucagon responses were measured during a 3-h 50-g OGTT (day A) and an IIGI (day B) in 10 patients with T2DM [age (mean ± SE), 51 ± 3 yr; body mass index, 33 ± 2 kg/m(2); HbA(1c), 6.5 ± 0.2%]. During four additional IIGIs, GIP (day C), GLP-1 (day D), GLP-2 (day E) and a combination of the three (day F) were infused intravenously. Isoglycemia during all six study days was obtained. As expected, no suppression of glucagon occurred during the initial phase of the OGTT, whereas significantly (P < 0.05) lower plasma levels of glucagon during the first 30 min of the IIGI (day B) were observed. The glucagon response during the IIGI + GIP + GLP-1 + GLP-2 infusion (day F) equaled the inappropriate glucagon response to OGTT (P = not significant). The separate GIP infusion (day C) elicited significant hypersecretion of glucagon, whereas GLP-1 infusion (day D) resulted in enhancement of glucagon suppression during IIGI. IIGI + GLP-2 infusion (day E) resulted in a glucagon response in the midrange between the glucagon responses to OGTT and IIGI. Our results indicate that the intestinal hormones, GIP, GLP-1, and GLP-2, may play a role in the inappropriate glucagon response to orally ingested glucose in T2DM with, especially, GIP, acting to increase glucagon secretion. SN - 1522-1555 UR - https://www.unboundmedicine.com/medline/citation/21386059/The_separate_and_combined_impact_of_the_intestinal_hormones_GIP_GLP_1_and_GLP_2_on_glucagon_secretion_in_type_2_diabetes_ L2 - https://journals.physiology.org/doi/10.1152/ajpendo.00665.2010?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -