GIP contributes to islet trihormonal abnormalities in type 2 diabetes.
BACKGROUND
Research and clinical treatments on type 2 diabetes mainly focus on insulin 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.


METHODS
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.


METHODS
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.


METHODS
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.
Laboratory of Clinical Investigation (C.W.C., J.O.O., O.D.C., J.M.E.) and Translational Gerontology Branch (L.F.), National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21225; and Department of Molecular Science and Technology (W.K.), Ajou University, Suwon 443-749, South Korea.
Chee W
CW
Chia
Juliana O
JO
Odetunde
Wook
W
Kim
Olga D
OD
Carlson
Luigi
L
Ferrucci
Josephine M
JM
Egan
D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010182:Pancreatic Diseases / Q000209:etiology* / Q000378:metabolism; D010187:Pancreatic Hormones / Q000378:metabolism*
D010187:Pancreatic Hormones; D005749:Gastric Inhibitory Polypeptide