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

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Daisuke Yabe, Akira Kuroe, Koin Watanabe, Masahiro Iwasaki, Akihiro Hamasaki, Yoshiyuki Hamamoto, Norio Harada, Shunsuke Yamane, Soushou Lee, Kenta Murotani, Carolyn F Deacon, Jens Juul Holst, Tsutomu Hirano, Nobuya Inagaki, Takeshi Kurose, Yutaka Seino

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.

Original languageEnglish
JournalJournal of Diabetes and its Complications
Pages (from-to)413-421
Number of pages9
Publication statusPublished - 2015

ID: 132046701