Early phase glucagon and insulin secretory abnormalities, but not incretin secretion, are similarly responsible for hyperglycemia after ingestion of nutrients

Abstract 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....

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Published in:Journal of diabetes and its complications 2015-04, Vol.29 (3), p.413-421
Main Authors: Yabe, Daisuke, Kuroe, Akira, Watanabe, Koin, Iwasaki, Masahiro, Hamasaki, Akihiro, Hamamoto, Yoshiyuki, Harada, Norio, Yamane, Shunsuke, Lee, Soushou, Murotani, Kenta, Deacon, Carolyn F, Holst, Jens J, Hirano, Tsutomu, Inagaki, Nobuya, Kurose, Takeshi, Seino, Yutaka
Format: Article
Language:English
Subjects:
Adult
Aged
Blood Glucose - metabolism
Body mass index
Eating
Endocrinology & Metabolism
Female
Food
GIP
GLP-1
Glucagon
Glucagon - metabolism
Glucose
Glucose Tolerance Test
Humans
Hyperglycemia
Hyperglycemia - etiology
Hyperglycemia - metabolism
Incretins - metabolism
Insulin
Insulin - metabolism
Insulin resistance
Insulin Secretion
Male
Middle Aged
Pancreas
Postprandial Period
Time Factors
Young Adult
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Summary:Abstract 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-AUC0–30 min and insulin-AUC0–30 min 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.
ISSN:1056-8727
1873-460X
DOI:10.1016/j.jdiacomp.2014.12.010