TY - JOUR
T1 - GIP contributes to islet trihormonal abnormalities in type 2 diabetes
AU - Chia, Chee W.
AU - Odetunde, Juliana O.
AU - Kim, Wook
AU - Carlson, Olga D.
AU - Ferrucci, Luigi
AU - Egan, Josephine M.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/7
Y1 - 2014/7
N2 - Context: Research and clinical treatmentsontype 2 diabetes mainly focusoninsulin deficiency with little attention paid to other islet hormones. Objective: This study tested the hypothesis that glucose-dependent insulinotropic polypeptide (GIP) is involved in diabetes-associated multiislet hormone dysregulation. Design: This paper included a case-control study involving 92 community-based volunteers from the Baltimore Longitudinal Study of Aging (BLSA): 23 with type 2 diabetes on glucose-lowering agents, 25 with newly diagnosed drug-naïve type 2 diabetes, 19 with prediabetes, and 25 with normal glucose tolerance; a separate intervention study with 13 non-BLSA volunteers with type 2 diabetes treated with diet alone, metformin, and/or metformin/sulfonylurea combination; a rodent study; and an in vitro cell line study. Interventions: An oral glucose tolerance test was performed in the BLSA participants. For the intervention study, saline (0.9% NaCl) or synthetic human GIP (20 ng · kg-1 · min-1) was administered to type 2 diabetes subjects for 180 minutes together with a meal, and plasma samples were obtained at predetermined intervals for 360 minutes. A bolus of GIP or placebo was given to C57BL/6 mice. Main Outcome Measures: Plasma glucose, insulin, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and GIP were measured. Results: After an oral glucose tolerance test, glucose, glucagon, PP, GLP-1, and GIP levels were significantly elevated in type 2 diabetes groups, compared with normal and prediabetes groups. GIP infusion in type 2 diabetes subjects was associated with significantly elevated PP levels compared with placebo. The GIP bolus given to C57BL/6 mice was followed by increased PP levels. GIP receptors were found in both human and mouse PP cells. Conclusions: Up-regulation of GIP production may play an important role in multihormonal dysregulation in type 2 diabetes, most likely through interaction with GIP receptors on islets.
AB - Context: Research and clinical treatmentsontype 2 diabetes mainly focusoninsulin deficiency with little attention paid to other islet hormones. Objective: This study tested the hypothesis that glucose-dependent insulinotropic polypeptide (GIP) is involved in diabetes-associated multiislet hormone dysregulation. Design: This paper included a case-control study involving 92 community-based volunteers from the Baltimore Longitudinal Study of Aging (BLSA): 23 with type 2 diabetes on glucose-lowering agents, 25 with newly diagnosed drug-naïve type 2 diabetes, 19 with prediabetes, and 25 with normal glucose tolerance; a separate intervention study with 13 non-BLSA volunteers with type 2 diabetes treated with diet alone, metformin, and/or metformin/sulfonylurea combination; a rodent study; and an in vitro cell line study. Interventions: An oral glucose tolerance test was performed in the BLSA participants. For the intervention study, saline (0.9% NaCl) or synthetic human GIP (20 ng · kg-1 · min-1) was administered to type 2 diabetes subjects for 180 minutes together with a meal, and plasma samples were obtained at predetermined intervals for 360 minutes. A bolus of GIP or placebo was given to C57BL/6 mice. Main Outcome Measures: Plasma glucose, insulin, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and GIP were measured. Results: After an oral glucose tolerance test, glucose, glucagon, PP, GLP-1, and GIP levels were significantly elevated in type 2 diabetes groups, compared with normal and prediabetes groups. GIP infusion in type 2 diabetes subjects was associated with significantly elevated PP levels compared with placebo. The GIP bolus given to C57BL/6 mice was followed by increased PP levels. GIP receptors were found in both human and mouse PP cells. Conclusions: Up-regulation of GIP production may play an important role in multihormonal dysregulation in type 2 diabetes, most likely through interaction with GIP receptors on islets.
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U2 - 10.1210/jc.2013-3994
DO - 10.1210/jc.2013-3994
M3 - Article
C2 - 24712564
AN - SCOPUS:84904060080
VL - 99
SP - 2477
EP - 2485
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 7
ER -