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

TY - JOUR

T1 - Early phase glucagon and insulin secretory abnormalities, but not incretin secretion, are similarly responsible for hyperglycemia after ingestion of nutrients

AU - Yabe, Daisuke

AU - Kuroe, Akira

AU - Watanabe, Koin

AU - Iwasaki, Masahiro

AU - Hamasaki, Akihiro

AU - Hamamoto, Yoshiyuki

AU - Harada, Norio

AU - Yamane, Shunsuke

AU - Lee, Soushou

AU - Murotani, Kenta

AU - Deacon, Carolyn F

AU - Holst, Jens Juul

AU - Hirano, Tsutomu

AU - Inagaki, Nobuya

AU - Kurose, Takeshi

AU - Seino, Yutaka

N1 - Copyright © 2015. Published by Elsevier Inc.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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 0-30min, unlike NGT and IGT, along with reduced insulin. In MTT, all three groups showed a rise in glucagon at 0-30min, 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.

AB - 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 0-30min, unlike NGT and IGT, along with reduced insulin. In MTT, all three groups showed a rise in glucagon at 0-30min, 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.

U2 - 10.1016/j.jdiacomp.2014.12.010

DO - 10.1016/j.jdiacomp.2014.12.010

M3 - Journal article

C2 - 25613093

SN - 1056-8727

VL - 29

SP - 413

EP - 421

JO - Journal of Diabetes and its Complications

JF - Journal of Diabetes and its Complications

ER -