REVIEWS   

Minerva Endocrinologica 2016 March;41(1):43-56

Copyright © 2016 EDIZIONI MINERVA MEDICA

language: English

Gastrointestinal dopamine as an anti-incretin and its possible role in bypass surgery as therapy for type 2 diabetes with associated obesity

Suleman CHAUDHRY ¹, Marilia BERNARDES ², Paul E. HARRIS ^{2, 3}, Antonella MAFFEI ^{2, 4} ✉

¹ Department of Surgery, Columbia University Medical Center, New York, NY, USA; ² Division of Endocrinology, Department of Medicine, Columbia University Medical Center New York, NY, USA; ³ Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, NY, USA; ⁴ Institute of Genetics and Biophysics Adriano Buzzati‑Traverso, Consiglio Nazionale delle Ricerche, Naples, Italy

The objective of this review was to summarize and integrate specific clinical observations from the field of gastric bypass surgery and recent findings in beta cell biology. When considered together, these data sets suggest a previously unrecognized physiological mechanism which may explain how Roux-en-Y gastric bypass (RYGB) surgery mediates the early rapid reversal of hyperglycemia, observed before weight loss, in certain type 2 diabetes mellitus (T2DM) patients. The novel mechanism is based on a recently recognized inhibitory circuit of glucose stimulated insulin secretion driven by DA stored in β-cell vesicles and the gut. We propose that DA and glucagon-like peptide 1 (GLP-1) represent two opposing arms of a glucose stimulated insulin secretion (GSIS) regulatory system and hypothesize that dopamine represents the “anti-incretin” hypothesized to explain the beneficial effects of bariatric surgery on T2DM. These new hypotheses and the research driven by them may directly impact our understanding of: 1) the mechanisms underlying improved glucose homeostasis seen before weight loss following bariatric surgery; and 2) the regulation of glucose stimulated insulin secretion within islets. On a practical level, these studies may result in the development of novels drugs to modulate insulin secretion and/or methods to quantitatively asses in real time beta cell function and mass.