PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery.
Roux-en-Y gastric bypass (RYGB) is a weight-reduction procedure resulting in rapid resolution of type 2 diabetes (T2D). The role of pancreatic islet function in this restoration of normoglycemia has not been fully elucidated. Using the diabetic Goto-Kakizaki (GK) rat model, we demonstrate that RYGB restores normal glucose regulation of glucagon and insulin secretion and normalizes islet morphology. Culture of isolated islets with serum from RYGB animals mimicked these effects, implicating a humoral factor. These latter effects were reversed following neutralization of the gut hormone peptide tyrosine tyrosine (PYY) but persisted in the presence of a glucagon-like peptide-1 (GLP-1) receptor antagonist. The effects of RYGB on secretion were replicated by chronic exposure of diabetic rat islets to PYY in vitro. These findings indicate that the mechanism underlying T2D remission may be mediated by PYY and suggest that drugs promoting PYY release or action may restore pancreatic islet function in T2D.
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, Oxon OX3 7LE, UK. Electronic address: reshma.ramracheya@ocdem.ox.ac.uk.
Reshma D
RD
Ramracheya
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, Oxon OX3 7LE, UK.
Laura J
LJ
McCulloch
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, Oxon OX3 7LE, UK.
Anne
A
Clark
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, Oxon OX3 7LE, UK.
David
D
Wiggins
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Helene
H
Johannessen
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Magnus Kringstad
MK
Olsen
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Xing
X
Cai
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Chun-Mei
CM
Zhao
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Duan
D
Chen
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, Oxon OX3 7LE, UK; Metabolic Research, Department of Physiology, Institute of Neuroscience and Physiology, University of Goteborg, Box 432, 40530 Göteborg, Sweden.
Patrik
P
Rorsman
D000328:Adult; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015390:Gastric Bypass; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008297:Male; D019894:Peptide YY / Q000378:metabolism*; D017208:Rats, Wistar; D014158:Transcription, Genetic
D007328:Insulin; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D005934:Glucagon