Function and expression of sulfonylurea, adrenergic, and glucagon-like peptide 1 receptors in isolated porcine islets

Amy C. Kelly, Leah V. Steyn, Jenna P. Kitzmann, Miranda J. Anderson, Kate R. Mueller, Nathaniel J. Hart, Ron Lynch, Klearchos K Papas, Sean W Limesand

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The scarcity of human cadaveric pancreata limits large-scale application of islet transplantation for patients with diabetes. Islets isolated from pathogen-free pigs provide an economical and abundant alternative source assuming immunologic barriers are appropriate. Membrane receptors involved in insulin secretion that also have potential as imaging targets were investigated in isolated porcine islets. Quantitative (q)PCR revealed that porcine islets express mRNA transcripts for sulfonylurea receptor 1 (Sur1), inward rectifying potassium channel (Kir6.2, associated with Sur1), glucagon-like peptide 1 receptor (GLP1R), and adrenergic receptor alpha 2A (ADRα2A). Receptor function was assessed in static incubations with stimulatory glucose concentrations, and in the presence of receptor agonists. Glibenclamide, an anti-diabetic sulfonylurea, and exendin-4, a GLP-1 mimetic, potentiated glucose-stimulated insulin secretion >2-fold. Conversely, epinephrine maximally reduced insulin secretion 72 ± 9% (P < 0.05) and had a half maximal inhibitory concentration of 60 nm in porcine islets (95% confidence interval of 45-830 nm). The epinephrine action was inhibited by the ADRα2A antagonist yohimbine. Our findings demonstrate that porcine islets express and are responsive to both stimulatory and inhibitory membrane localized receptors, which can be used as imaging targets after transplantation or to modify insulin secretion.

Original languageEnglish (US)
Pages (from-to)385-391
Number of pages7
JournalXenotransplantation
Volume21
Issue number4
DOIs
StatePublished - 2014

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Adrenergic Agents
Swine
Adrenergic alpha-2 Receptors
Sulfonylurea Receptors
Insulin
Epinephrine
Glucose
Islets of Langerhans Transplantation
Glucagon-Like Peptide 1
Membranes
Yohimbine
Glyburide
Potassium Channels
Pancreas
Transplantation
Glucagon-Like Peptide-1 Receptor
Confidence Intervals
Polymerase Chain Reaction
Messenger RNA

Keywords

  • epinephrine
  • exendin-4
  • glibenclamide
  • insulin secretion
  • porcine islet

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Function and expression of sulfonylurea, adrenergic, and glucagon-like peptide 1 receptors in isolated porcine islets. / Kelly, Amy C.; Steyn, Leah V.; Kitzmann, Jenna P.; Anderson, Miranda J.; Mueller, Kate R.; Hart, Nathaniel J.; Lynch, Ron; Papas, Klearchos K; Limesand, Sean W.

In: Xenotransplantation, Vol. 21, No. 4, 2014, p. 385-391.

Research output: Contribution to journalArticle

Kelly, Amy C. ; Steyn, Leah V. ; Kitzmann, Jenna P. ; Anderson, Miranda J. ; Mueller, Kate R. ; Hart, Nathaniel J. ; Lynch, Ron ; Papas, Klearchos K ; Limesand, Sean W. / Function and expression of sulfonylurea, adrenergic, and glucagon-like peptide 1 receptors in isolated porcine islets. In: Xenotransplantation. 2014 ; Vol. 21, No. 4. pp. 385-391.
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