Glucagon-like peptide 1 (GLP-1).

Background: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability.

Discovery, characterization, and clinical development of the glucagon-like peptides.

The discovery, characterization, and clinical development of glucagon-like-peptide-1 (GLP-1) spans more than 30 years and includes contributions from multiple investigators, science recognized by the 2017 Harrington Award Prize for Innovation in Medicine. Herein, we provide perspectives on the historical events and key experimental findings establishing the biology of GLP-1 as an insulin-stimulating glucoregulatory hormone. Important attributes of GLP-1 action and enteroendocrine science are reviewed, with emphasis on mechanistic advances and clinical proof-of-concept studies.

Pancreas and Not Gut Mediates the GLP-1-Induced Glucoincretin Effect.

The gut is believed to be the source of GLP-1 that augments insulin secretion in response to oral nutrients. In this issue of Cell Metabolism, Chambers et al. (2017) shift the paradigm by finding that GLP-1 produced within the islets of the pancreas, and not the gut, is responsible for the incretin effect in mice.

Evolving function and potential of pancreatic alpha cells.

The alpha cells that co-occupy the islets in association with beta cells have been long recognized as the source of glucagon, a hyperglycemia-producing and diabetogenic hormone. Although the mechanisms that control the functions of alpha cells, glucagon secretion, and the role of glucagon in diabetes have remained somewhat enigmatic over the fifty years since their discovery, seminal findings during the past few years have moved alpha cells into the spotlight of scientific discovery. These findings obtained largely from studies in mice are: Alpha cells have the capacity to trans-differentiate into insulin-producing beta cells.

Does GLP-1 suppress its own basal secretion?

Purpose/aim: Negative feedback controls in endocrine regulatory systems are well recognized. The incretins and their role in glucose regulation have been of major interest recently. Whether the same negative control system applies to the regulation of incretin secretion is not clear.