Journal
JOURNAL OF DIABETES AND ITS COMPLICATIONS
Volume 29, Issue 3, Pages 413-421Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jdiacomp.2014.12.010
Keywords
Insulin; Glucagon; GLP-1; GIP; Hyperglycemia
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Funding
- Merck, Sharp and Dohme
- NNF Center for Basic Metabolic Research [Holst Group] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [25860748, 25461344] Funding Source: KAKEN
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Aims: Hypersecretion of glucagon and reduced insulin secretion both contribute to hyperglycemia in type 2 diabetes (T2DM). However, the relative contributions of impaired glucagon and insulin secretions in glucose excursions at the various stages of T2DM development remain to be determined. Methods: The responses of glucagon and insulin as well as those of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were examined before and after ingestion of glucose or mixed meal in Japanese subjects with normal or impaired glucose tolerance (NGT and IGT) and in non-obese, untreated T2DM of short duration. Results: In OGTT, T2DM showed a rise in glucagon at 0-30 min, unlike NGT and IGT, along with reduced insulin. In MTT, all three groups showed a rise in glucagon at 0-30 min, with that in T2DM being highest, while T2DM showed a significant reduction in insulin. Linear regression analyses revealed that glucose area under the curve (AUC)(0-120) min was associated with glucagon-AUC(0-30) min and insulin-AUC(0-30min) in both OGTT and MTT. Total and biologically intact GIP and GLP-1 levels were similar among the three groups. Conclusions: Disordered early phase insulin and glucagon secretions but not incretin secretion are involved in hyperglycemia after ingestion of nutrients in T2DM of even a short duration. (C) 2015 The authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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