title: Early phase glucagon and insulin secretory abnormalities, but not incretin secretion, are similarly responsible for hyperglycemia after ingestion of nutrients.
abstract: OBJECTIVE
  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.affiliation: 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.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yabe
authors.affiliation: Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kuroe
authors.affiliation: Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan.
authors.forename: Koin
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: 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.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogo-in Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hamasaki
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogo-in Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hamamoto
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogo-in Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Harada
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogo-in Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamane
authors.affiliation: Department of Diabetes, Metabolism and Endocrinology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Soushou
authors.initials: S
authors.lastname: Lee
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Murotani
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Diabetes, Metabolism and Endocrinology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogo-in Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka 553-0003, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurose
authors.affiliation: 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.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating; D005260:Female; D005502:Food; D005934:Glucagon / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology* / Q000378:metabolism; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D005934:Glucagon
keywords: GIP; GLP-1; Glucagon; Hyperglycemia; Insulin