4.4 Review

Nutrient regulation of glucagon secretion: involvement in metabolism and diabetes

Journal

NUTRITION RESEARCH REVIEWS
Volume 27, Issue 1, Pages 48-62

Publisher

CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0954422414000031

Keywords

Pancreatic alpha-cells; Diabetes; Glucagon secretion

Funding

  1. Ministerio de Ciencia e Innovacion [BFU2010-21773, BFU2011-28358]
  2. Generalitat Valenciana [PROM-ETEO/2011/080, ACOMP/2013/022]
  3. European Foundation for the Study of Diabetes (EFSD/BI Basic Programme)

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Glucose homeostasis is precisely regulated by glucagon and insulin, which are released by pancreatic alpha- and beta-cells, respectively. While beta-cells have been the focus of intense research, less is known about alpha-cell function and the actions of glucagon. In recent years, the study of this endocrine cell type has experienced a renewed drive. The present review contains a summary of established concepts as well as new information about the regulation of alpha-cells by glucose, amino acids, fatty acids and other nutrients, focusing especially on glucagon release, glucagon synthesis and alpha-cell survival. We have also discussed the role of glucagon in glucose homeostasis and in energy and lipid metabolism as well as its potential as a modulator of food intake and body weight. In addition to the well-established action on the liver, we discuss the effects of glucagon in other organs, where the glucagon receptor is expressed. These tissues include the heart, kidneys, adipose tissue, brain, small intestine and the gustatory epithelium. Alterations in alpha-cell function and abnormal glucagon concentrations are present in diabetes and are thought to aggravate the hyperglycaemic state of diabetic patients. In this respect, several experimental approaches in diabetic models have shown important beneficial results in improving hyperglycaemia after the modulation of glucagon secretion or action. Moreover, glucagon receptor agonism has also been used as a therapeutic strategy to treat obesity.

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