GIP contributes to islet trihormonal abnormalities in type 2 diabetes

Chee W. Chia, Juliana O. Odetunde, Wook Kim, Olga D. Carlson, Luigi Ferrucci, Josephine M. Egan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2477-2485
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number7
DOIs
StatePublished - 2014
Externally publishedYes

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Medical problems
Type 2 Diabetes Mellitus
Glucose
Peptides
Pancreatic Polypeptide
Longitudinal Studies
Prediabetic State
Baltimore
Glucagon-Like Peptide 1
Metformin
Glucose Tolerance Test
Glucagon
Inbred C57BL Mouse
Aging of materials
Volunteers
Pancreatic Polypeptide-Secreting Cells
Placebos
Hormones
Plasmas
Nutrition

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Chia, C. W., Odetunde, J. O., Kim, W., Carlson, O. D., Ferrucci, L., & Egan, J. M. (2014). GIP contributes to islet trihormonal abnormalities in type 2 diabetes. Journal of Clinical Endocrinology and Metabolism, 99(7), 2477-2485. https://doi.org/10.1210/jc.2013-3994

GIP contributes to islet trihormonal abnormalities in type 2 diabetes. / Chia, Chee W.; Odetunde, Juliana O.; Kim, Wook; Carlson, Olga D.; Ferrucci, Luigi; Egan, Josephine M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 7, 2014, p. 2477-2485.

Research output: Contribution to journalArticle

Chia, CW, Odetunde, JO, Kim, W, Carlson, OD, Ferrucci, L & Egan, JM 2014, 'GIP contributes to islet trihormonal abnormalities in type 2 diabetes', Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 7, pp. 2477-2485. https://doi.org/10.1210/jc.2013-3994
Chia, Chee W. ; Odetunde, Juliana O. ; Kim, Wook ; Carlson, Olga D. ; Ferrucci, Luigi ; Egan, Josephine M. / GIP contributes to islet trihormonal abnormalities in type 2 diabetes. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 7. pp. 2477-2485.
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abstract = "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-na{\"i}ve 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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