Daisuke Yabe1, Akira Kuroe2, Koin Watanabe2, Masahiro Iwasaki3, Akihiro Hamasaki4, Yoshiyuki Hamamoto4, Norio Harada4, Shunsuke Yamane4, Soushou Lee5, Kenta Murotani6, Carolyn F Deacon7, Jens J Holst7, Tsutomu Hirano5, Nobuya Inagaki4, Takeshi Kurose2, Yutaka Seino8. 1. Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan; Center for Metabolism and Clinical Nutrition, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan; Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojimaminamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: ydaisuke-kyoto@umin.ac.jp. 2. Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan. 3. Center for Metabolism and Clinical Nutrition, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan; Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojimaminamimachi, Chuo-ku, Kobe 650-0047, Japan. 4. Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogo-in Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. 5. Department of Diabetes, Metabolism and Endocrinology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. 6. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan. 7. Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, Blegdamsvej 3, 2200 Copenhagen N, Denmark. 8. Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan. Electronic address: seino.yutaka@e2.kepco.co.jp.
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.
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.
Authors: A D M Koopman; F Rutters; S P Rauh; G Nijpels; J J Holst; J W Beulens; M Alssema; J M Dekker Journal: PLoS One Date: 2018-01-11 Impact factor: 3.240