Paracrine Interactions within the Pancreatic Islet Determine the Glycemic Set Point

Rayner Rodriguez Diaz, Ruth Molano, Jonathan R. Weitz, Midhat H Abdulreda, Dora Berman-Weinberg, Barbara Leibiger, Ingo B. Leibiger, Norma S Kenyon, Camillo Ricordi, Antonello Pileggi, Diego A Caicedo-Vierkant, Per Olof Berggren

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Every animal species has a signature blood glucose level or glycemic set point. These set points are different, and the normal glycemic levels (normoglycemia) of one species would be life threatening for other species. Mouse normoglycemia can be considered diabetic for humans. The biological determinants of the glycemic set point remain unclear. Here we show that the pancreatic islet imposes its glycemic set point on the organism, making it the bona fide glucostat in the body. Moreover, and in contrast to rodent islets, glucagon input from the alpha cell to the insulin-secreting beta cell is necessary to fine-tune the distinctive human set point. These findings affect transplantation and regenerative approaches to treat diabetes because restoring normoglycemia may require more than replacing only the beta cells. Furthermore, therapeutic strategies using glucagon receptor antagonists as hypoglycemic agents need to be reassessed, as they may reset the overall glucostat in the organism. It is not known if there is a leading organ that maintains blood glucose levels within the narrow physiological range. Rodriguez-Diaz and colleagues show that the pancreatic islet serves as the systemic glucostat and that paracrine glucagon input from alpha cells is essential for setting the glycemic set point. Therapeutic strategies using glucagon receptor antagonists to lower glycemia should thus be reassessed.

Original languageEnglish (US)
Pages (from-to)549-558.e4
JournalCell Metabolism
Volume27
Issue number3
DOIs
StatePublished - Mar 6 2018

Fingerprint

Glucagon Receptors
Islets of Langerhans
Glucagon
Blood Glucose
Insulin-Secreting Cells
Hypoglycemic Agents
Rodentia
Transplantation
Therapeutics

Keywords

  • alpha cell
  • beta cell
  • glucagon
  • glucose homeostasis
  • glycemia
  • glycemic set point
  • human pancreatic islet
  • humanized mouse
  • insulin secretion
  • paracrine signaling

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Paracrine Interactions within the Pancreatic Islet Determine the Glycemic Set Point. / Rodriguez Diaz, Rayner; Molano, Ruth; Weitz, Jonathan R.; Abdulreda, Midhat H; Berman-Weinberg, Dora; Leibiger, Barbara; Leibiger, Ingo B.; Kenyon, Norma S; Ricordi, Camillo; Pileggi, Antonello; Caicedo-Vierkant, Diego A; Berggren, Per Olof.

In: Cell Metabolism, Vol. 27, No. 3, 06.03.2018, p. 549-558.e4.

Research output: Contribution to journalArticle

Rodriguez Diaz, Rayner ; Molano, Ruth ; Weitz, Jonathan R. ; Abdulreda, Midhat H ; Berman-Weinberg, Dora ; Leibiger, Barbara ; Leibiger, Ingo B. ; Kenyon, Norma S ; Ricordi, Camillo ; Pileggi, Antonello ; Caicedo-Vierkant, Diego A ; Berggren, Per Olof. / Paracrine Interactions within the Pancreatic Islet Determine the Glycemic Set Point. In: Cell Metabolism. 2018 ; Vol. 27, No. 3. pp. 549-558.e4.
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