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

Joana Almaca, Judith Molina, Danusa Menegaz, Alexey N. Pronin, Alejandro Tamayo, Vladlen Z Slepak, Per Olof Berggren, Diego A Caicedo-Vierkant

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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
Volume17
Issue number12
DOIs
StatePublished - Dec 20 2016

Fingerprint

Glucagon
Serotonin
Glucose
Physiology
Nutrition
Medical problems
Hypoglycemic Agents
Cyclic AMP
High Fat Diet
Blindness
Islets of Langerhans
Chemical activation
Fats
Modulation
Hormones
Pharmacology
Pregnancy
Pharmaceutical Preparations
serotonin 1F receptor

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells. / Almaca, Joana; Molina, Judith; Menegaz, Danusa; Pronin, Alexey N.; Tamayo, Alejandro; Slepak, Vladlen Z; Berggren, Per Olof; Caicedo-Vierkant, Diego A.

In: Cell Reports, Vol. 17, No. 12, 20.12.2016, p. 3281-3291.

Research output: Contribution to journalArticle

Almaca, Joana ; Molina, Judith ; Menegaz, Danusa ; Pronin, Alexey N. ; Tamayo, Alejandro ; Slepak, Vladlen Z ; Berggren, Per Olof ; Caicedo-Vierkant, Diego A. / Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells. In: Cell Reports. 2016 ; Vol. 17, No. 12. pp. 3281-3291.
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