Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

β-Cell failure in type 2 diabetes (T2D) was recently proposed to involve dedifferentiation of β-cells and ectopic expression of other islet hormones, including somatostatin and glucagon. Here we show that gastrin, a stomach hormone typically expressed in the pancreas only during embryogenesis, is expressed in islets of diabetic rodents and humans with T2D. Although gastrin in mice is expressed in insulin+ cells, gastrin expression in humans with T2D occurs in both insulin+ and somatostatin+ cells. Genetic lineage tracing in mice indicates that gastrin expression is turned on in a subset of differentiated β-cells after exposure to severe hyperglycemia. Gastrin expression in adult β-cells does not involve the endocrine progenitor cell regulator neurogenin3 but requires membrane depolarization, calcium influx, and calcineurin signaling. In vivo and in vitro experiments show that gastrin expression is rapidly eliminated upon exposure of β-cells to normal glucose levels. These results reveal the fetal hormone gastrin as a novel marker for reversible human β-cell reprogramming in diabetes.

Original publication

DOI

10.2337/db16-0641

Type

Journal article

Journal

Diabetes

Publication Date

02/2017

Volume

66

Pages

426 - 436

Keywords

Aged, Aged, 80 and over, Animals, Basic Helix-Loop-Helix Transcription Factors, Case-Control Studies, Diabetes Mellitus, Diabetes Mellitus, Type 2, Gastrins, Gene Expression Regulation, Developmental, Gerbillinae, Humans, Immunohistochemistry, Insulin-Secreting Cells, Islets of Langerhans, Male, Mice, Nerve Tissue Proteins, Real-Time Polymerase Chain Reaction, Somatostatin-Secreting Cells, Stem Cells