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β Cell tone is defined by proglucagon peptides through cAMP signaling.

Publication ,  Journal Article
Capozzi, ME; Svendsen, B; Encisco, SE; Lewandowski, SL; Martin, MD; Lin, H; Jaffe, JL; Coch, RW; Haldeman, JM; MacDonald, PE; Merrins, MJ ...
Published in: JCI Insight
March 7, 2019

Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis. Here, we demonstrate the importance of proglucagon-derived peptides (PGDPs) for α to β cell communication and control of insulin secretion. Signaling through this system occurs through both the glucagon-like peptide receptor (Glp1r) and glucagon receptor (Gcgr). Loss of PGDPs, or blockade of their receptors, decreases insulin secretion in response to both metabolic and nonmetabolic stimulation of mouse and human islets. This effect is due to reduced β cell cAMP and affects the quantity but not dynamics of insulin release, indicating that PGDPs dictate the magnitude of insulin output in an isolated islet. In healthy mice, additional factors that stimulate cAMP can compensate for loss of PGDP signaling; however, input from α cells is essential to maintain glucose tolerance during the metabolic stress induced by high-fat feeding. These findings demonstrate an essential role for α cell regulation of β cells, raising the possibility that abnormal paracrine signaling contributes to impaired insulin secretion in diabetes. Moreover, these findings support reconsideration of the role for α cells in postprandial glucose control.

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

March 7, 2019

Volume

4

Issue

5

Location

United States

Related Subject Headings

  • Signal Transduction
  • Proglucagon
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Insulin-Secreting Cells
  • Insulin
  • Humans
  • Homeostasis
  • Glucose
 

Citation

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Capozzi, M. E., Svendsen, B., Encisco, S. E., Lewandowski, S. L., Martin, M. D., Lin, H., … Campbell, J. E. (2019). β Cell tone is defined by proglucagon peptides through cAMP signaling. JCI Insight, 4(5). https://doi.org/10.1172/jci.insight.126742
Capozzi, Megan E., Berit Svendsen, Sara E. Encisco, Sophie L. Lewandowski, Mackenzie D. Martin, Haopeng Lin, Justin L. Jaffe, et al. “β Cell tone is defined by proglucagon peptides through cAMP signaling.JCI Insight 4, no. 5 (March 7, 2019). https://doi.org/10.1172/jci.insight.126742.
Capozzi ME, Svendsen B, Encisco SE, Lewandowski SL, Martin MD, Lin H, et al. β Cell tone is defined by proglucagon peptides through cAMP signaling. JCI Insight. 2019 Mar 7;4(5).
Capozzi, Megan E., et al. “β Cell tone is defined by proglucagon peptides through cAMP signaling.JCI Insight, vol. 4, no. 5, Mar. 2019. Pubmed, doi:10.1172/jci.insight.126742.
Capozzi ME, Svendsen B, Encisco SE, Lewandowski SL, Martin MD, Lin H, Jaffe JL, Coch RW, Haldeman JM, MacDonald PE, Merrins MJ, D’Alessio DA, Campbell JE. β Cell tone is defined by proglucagon peptides through cAMP signaling. JCI Insight. 2019 Mar 7;4(5).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

March 7, 2019

Volume

4

Issue

5

Location

United States

Related Subject Headings

  • Signal Transduction
  • Proglucagon
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Insulin-Secreting Cells
  • Insulin
  • Humans
  • Homeostasis
  • Glucose