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Exogenous Glucose–Dependent Insulinotropic Polypeptide Worsens Post prandial Hyperglycemia in T ype 2 Diabetes

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP), unlike glucagon-like peptide (GLP)-1, lacks glucose-lowering properties in patients with type 2 diabetes. We designed this study to elucidate the underlying pathophysiology. RESEARCH DESIGN AND METHODS: Twenty-two insulin-naïve subjects...

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Autores principales: Chia, Chee W., Carlson, Olga D., Kim, Wook, Shin, Yu-Kyong, Charles, Cornelia P., Kim, Hee Seung, Melvin, Denise L., Egan, Josephine M.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682676/
https://www.ncbi.nlm.nih.gov/pubmed/19276444
http://dx.doi.org/10.2337/db08-0958
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author Chia, Chee W.
Carlson, Olga D.
Kim, Wook
Shin, Yu-Kyong
Charles, Cornelia P.
Kim, Hee Seung
Melvin, Denise L.
Egan, Josephine M.
author_facet Chia, Chee W.
Carlson, Olga D.
Kim, Wook
Shin, Yu-Kyong
Charles, Cornelia P.
Kim, Hee Seung
Melvin, Denise L.
Egan, Josephine M.
author_sort Chia, Chee W.
collection PubMed
description OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP), unlike glucagon-like peptide (GLP)-1, lacks glucose-lowering properties in patients with type 2 diabetes. We designed this study to elucidate the underlying pathophysiology. RESEARCH DESIGN AND METHODS: Twenty-two insulin-naïve subjects with type 2 diabetes were given either synthetic human GIP (20 ng · kg(−1) · min(−1)) or placebo (normal saline) over 180 min, starting with the first bite of a mixed meal (plus 1 g of acetaminophen) on two separate occasions. Frequent blood samples were obtained over 6 h to determine plasma GIP, GLP-1, glucose, insulin, glucagon, resistin, and acetaminophen levels. RESULTS: Compared with placebo, GIP induced an early postprandial increase in insulin levels. Intriguingly, GIP also induced an early postprandial augmentation in glucagon, a significant elevation in late postprandial glucose, and a decrease in late postprandial GLP-1 levels. Resistin and acetaminophen levels were comparable in both interventions. By immunocytochemistry, GIP receptors were present on human and mouse α-cells. In αTC1 cell line, GIP induced an increase in intracellular cAMP and glucagon secretion. CONCLUSIONS: GIP, given to achieve supraphysiological plasma levels, still had an early, short-lived insulinotropic effect in type 2 diabetes. However, with a concomitant increase in glucagon, the glucose-lowering effect was lost. GIP infusion further worsened hyperglycemia postprandially, most likely through its suppressive effect on GLP-1. These findings make it unlikely that GIP or GIP receptor agonists will be useful in treating the hyperglycemia of patients with type 2 diabetes.
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spelling pubmed-26826762010-06-01 Exogenous Glucose–Dependent Insulinotropic Polypeptide Worsens Post prandial Hyperglycemia in T ype 2 Diabetes Chia, Chee W. Carlson, Olga D. Kim, Wook Shin, Yu-Kyong Charles, Cornelia P. Kim, Hee Seung Melvin, Denise L. Egan, Josephine M. Diabetes Original Article OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP), unlike glucagon-like peptide (GLP)-1, lacks glucose-lowering properties in patients with type 2 diabetes. We designed this study to elucidate the underlying pathophysiology. RESEARCH DESIGN AND METHODS: Twenty-two insulin-naïve subjects with type 2 diabetes were given either synthetic human GIP (20 ng · kg(−1) · min(−1)) or placebo (normal saline) over 180 min, starting with the first bite of a mixed meal (plus 1 g of acetaminophen) on two separate occasions. Frequent blood samples were obtained over 6 h to determine plasma GIP, GLP-1, glucose, insulin, glucagon, resistin, and acetaminophen levels. RESULTS: Compared with placebo, GIP induced an early postprandial increase in insulin levels. Intriguingly, GIP also induced an early postprandial augmentation in glucagon, a significant elevation in late postprandial glucose, and a decrease in late postprandial GLP-1 levels. Resistin and acetaminophen levels were comparable in both interventions. By immunocytochemistry, GIP receptors were present on human and mouse α-cells. In αTC1 cell line, GIP induced an increase in intracellular cAMP and glucagon secretion. CONCLUSIONS: GIP, given to achieve supraphysiological plasma levels, still had an early, short-lived insulinotropic effect in type 2 diabetes. However, with a concomitant increase in glucagon, the glucose-lowering effect was lost. GIP infusion further worsened hyperglycemia postprandially, most likely through its suppressive effect on GLP-1. These findings make it unlikely that GIP or GIP receptor agonists will be useful in treating the hyperglycemia of patients with type 2 diabetes. American Diabetes Association 2009-06 2009-03-10 /pmc/articles/PMC2682676/ /pubmed/19276444 http://dx.doi.org/10.2337/db08-0958 Text en © 2009 by the American Diabetes Association.
spellingShingle Original Article
Chia, Chee W.
Carlson, Olga D.
Kim, Wook
Shin, Yu-Kyong
Charles, Cornelia P.
Kim, Hee Seung
Melvin, Denise L.
Egan, Josephine M.
Exogenous Glucose–Dependent Insulinotropic Polypeptide Worsens Post prandial Hyperglycemia in T ype 2 Diabetes
title Exogenous Glucose–Dependent Insulinotropic Polypeptide Worsens Post prandial Hyperglycemia in T ype 2 Diabetes
title_full Exogenous Glucose–Dependent Insulinotropic Polypeptide Worsens Post prandial Hyperglycemia in T ype 2 Diabetes
title_fullStr Exogenous Glucose–Dependent Insulinotropic Polypeptide Worsens Post prandial Hyperglycemia in T ype 2 Diabetes
title_full_unstemmed Exogenous Glucose–Dependent Insulinotropic Polypeptide Worsens Post prandial Hyperglycemia in T ype 2 Diabetes
title_short Exogenous Glucose–Dependent Insulinotropic Polypeptide Worsens Post prandial Hyperglycemia in T ype 2 Diabetes
title_sort exogenous glucose–dependent insulinotropic polypeptide worsens post prandial hyperglycemia in t ype 2 diabetes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682676/
https://www.ncbi.nlm.nih.gov/pubmed/19276444
http://dx.doi.org/10.2337/db08-0958
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