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cAMP signalling in insulin and glucagon secretion
Author(s) -
Tengholm Anders,
Gylfe Erik
Publication year - 2017
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12993
Subject(s) - glucagon , second messenger system , endocrinology , adenylyl cyclase , medicine , insulin , guanine nucleotide exchange factor , protein kinase a , phosphodiesterase , secretion , forskolin , microbiology and biotechnology , hormone , ibmx , chemistry , biology , signal transduction , kinase , biochemistry , stimulation , enzyme
The “second messenger” archetype cAMP is one of the most important cellular signalling molecules with central functions including the regulation of insulin and glucagon secretion from the pancreatic β‐ and α‐cells, respectively. cAMP is generally considered as an amplifier of insulin secretion triggered by Ca 2+ elevation in the β‐cells. Both messengers are also positive modulators of glucagon release from α‐cells, but in this case cAMP may be the important regulator and Ca 2+ have a more permissive role. The actions of cAMP are mediated by protein kinase A (PKA) and the guanine nucleotide exchange factor Epac. The present review focuses on how cAMP is regulated by nutrients, hormones and neural factors in β‐ and α‐cells via adenylyl cyclase‐catalysed generation and phosphodiesterase‐mediated degradation. We will also discuss how PKA and Epac affect ion fluxes and the secretory machinery to transduce the stimulatory effects on insulin and glucagon secretion. Finally, we will briefly describe disturbances of the cAMP system associated with diabetes and how cAMP signalling can be targeted to normalize hypo‐ and hypersecretion of insulin and glucagon, respectively, in diabetic patients.