Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells

Joana Almaça, Judith Molina, Danusa Menegaz, Alexey N. Pronin, Alejandro Tamayo, Vladlen Slepak, Per Olof Berggren, Alejandro Caicedo

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


In the pancreatic islet, serotonin is an autocrine signal increasing beta cell mass during metabolic challenges such as those associated with pregnancy or high-fat diet. It is still unclear whether serotonin is relevant for regular islet physiology and hormone secretion. Here, we show that human beta cells produce and secrete serotonin when stimulated with increases in glucose concentration. Serotonin secretion from beta cells decreases cyclic AMP (cAMP) levels in neighboring alpha cells via 5-HT1F receptors and inhibits glucagon secretion. Without serotonergic input, alpha cells lose their ability to regulate glucagon secretion in response to changes in glucose concentration, suggesting that diminished serotonergic control of alpha cells can cause glucose blindness and the uncontrolled glucagon secretion associated with diabetes. Supporting this model, pharmacological activation of 5-HT1F receptors reduces glucagon secretion and has hypoglycemic effects in diabetic mice. Thus, modulation of serotonin signaling in the islet represents a drug intervention opportunity.

Original languageEnglish (US)
Pages (from-to)3281-3291
Number of pages11
JournalCell Reports
Issue number12
StatePublished - Dec 20 2016


  • alpha cell
  • beta cell
  • diabetes
  • glucagon secretion
  • insulin secretion
  • pancreatic islet
  • paracrine signal
  • serotonin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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