PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic β-cells

Claudia Miele, Gregory Alexander Raciti, Angela Cassese, Chiara Romano, Ferdinando Giacco, Francesco Oriente, Flora Paturzo, Francesco Andreozzi, Assunta Zabatta, Giancarlo Troncone, Fatima Bosch, Anna Pujol, Hervé Chneiweiss, Pietro Formisano, Francesco Beguinot

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (ped/pea-15) gene is overexpressed in human diabetes and causes this abnormality in mice. Transgenic mice with β-cell-specific overexpression of ped/pea-15 (β-tg) exhibited decreased glucose tolerance but were not insulin resistant. However, they showed impaired insulin response to hyperglycemia. Islets from the β-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-ζ by glucose in mouse islets and in β-cells of the MIN-6 and INS-1 lines. Rescue of PKC-ζ activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing β-cells. Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-ζ by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic β-cells. Overexpression of PED/PEA-15 dysregulates β-cell function and is sufficient to impair glucose tolerance in mice.

Original languageEnglish (US)
Pages (from-to)622-633
Number of pages12
JournalDiabetes
Volume56
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Potassium Channels
Insulin
Glucose
Peas
Phosphoproteins
Protein Kinase C
Messenger RNA
Islets of Langerhans
Astrocytes
Hyperglycemia
Transgenic Mice
Genes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Miele, C., Raciti, G. A., Cassese, A., Romano, C., Giacco, F., Oriente, F., ... Beguinot, F. (2007). PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic β-cells. Diabetes, 56(3), 622-633. https://doi.org/10.2337/db06-1260

PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic β-cells. / Miele, Claudia; Raciti, Gregory Alexander; Cassese, Angela; Romano, Chiara; Giacco, Ferdinando; Oriente, Francesco; Paturzo, Flora; Andreozzi, Francesco; Zabatta, Assunta; Troncone, Giancarlo; Bosch, Fatima; Pujol, Anna; Chneiweiss, Hervé; Formisano, Pietro; Beguinot, Francesco.

In: Diabetes, Vol. 56, No. 3, 03.2007, p. 622-633.

Research output: Contribution to journalArticle

Miele, C, Raciti, GA, Cassese, A, Romano, C, Giacco, F, Oriente, F, Paturzo, F, Andreozzi, F, Zabatta, A, Troncone, G, Bosch, F, Pujol, A, Chneiweiss, H, Formisano, P & Beguinot, F 2007, 'PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic β-cells', Diabetes, vol. 56, no. 3, pp. 622-633. https://doi.org/10.2337/db06-1260
Miele, Claudia ; Raciti, Gregory Alexander ; Cassese, Angela ; Romano, Chiara ; Giacco, Ferdinando ; Oriente, Francesco ; Paturzo, Flora ; Andreozzi, Francesco ; Zabatta, Assunta ; Troncone, Giancarlo ; Bosch, Fatima ; Pujol, Anna ; Chneiweiss, Hervé ; Formisano, Pietro ; Beguinot, Francesco. / PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic β-cells. In: Diabetes. 2007 ; Vol. 56, No. 3. pp. 622-633.
@article{91fc97b2521a486bbf02d706c3ec5a5c,
title = "PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic β-cells",
abstract = "The phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (ped/pea-15) gene is overexpressed in human diabetes and causes this abnormality in mice. Transgenic mice with β-cell-specific overexpression of ped/pea-15 (β-tg) exhibited decreased glucose tolerance but were not insulin resistant. However, they showed impaired insulin response to hyperglycemia. Islets from the β-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-ζ by glucose in mouse islets and in β-cells of the MIN-6 and INS-1 lines. Rescue of PKC-ζ activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing β-cells. Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-ζ by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic β-cells. Overexpression of PED/PEA-15 dysregulates β-cell function and is sufficient to impair glucose tolerance in mice.",
author = "Claudia Miele and Raciti, {Gregory Alexander} and Angela Cassese and Chiara Romano and Ferdinando Giacco and Francesco Oriente and Flora Paturzo and Francesco Andreozzi and Assunta Zabatta and Giancarlo Troncone and Fatima Bosch and Anna Pujol and Herv{\'e} Chneiweiss and Pietro Formisano and Francesco Beguinot",
year = "2007",
month = "3",
doi = "10.2337/db06-1260",
language = "English (US)",
volume = "56",
pages = "622--633",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "3",

}

TY - JOUR

T1 - PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic β-cells

AU - Miele, Claudia

AU - Raciti, Gregory Alexander

AU - Cassese, Angela

AU - Romano, Chiara

AU - Giacco, Ferdinando

AU - Oriente, Francesco

AU - Paturzo, Flora

AU - Andreozzi, Francesco

AU - Zabatta, Assunta

AU - Troncone, Giancarlo

AU - Bosch, Fatima

AU - Pujol, Anna

AU - Chneiweiss, Hervé

AU - Formisano, Pietro

AU - Beguinot, Francesco

PY - 2007/3

Y1 - 2007/3

N2 - The phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (ped/pea-15) gene is overexpressed in human diabetes and causes this abnormality in mice. Transgenic mice with β-cell-specific overexpression of ped/pea-15 (β-tg) exhibited decreased glucose tolerance but were not insulin resistant. However, they showed impaired insulin response to hyperglycemia. Islets from the β-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-ζ by glucose in mouse islets and in β-cells of the MIN-6 and INS-1 lines. Rescue of PKC-ζ activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing β-cells. Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-ζ by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic β-cells. Overexpression of PED/PEA-15 dysregulates β-cell function and is sufficient to impair glucose tolerance in mice.

AB - The phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (ped/pea-15) gene is overexpressed in human diabetes and causes this abnormality in mice. Transgenic mice with β-cell-specific overexpression of ped/pea-15 (β-tg) exhibited decreased glucose tolerance but were not insulin resistant. However, they showed impaired insulin response to hyperglycemia. Islets from the β-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-ζ by glucose in mouse islets and in β-cells of the MIN-6 and INS-1 lines. Rescue of PKC-ζ activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing β-cells. Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-ζ by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic β-cells. Overexpression of PED/PEA-15 dysregulates β-cell function and is sufficient to impair glucose tolerance in mice.

UR - http://www.scopus.com/inward/record.url?scp=33847388518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847388518&partnerID=8YFLogxK

U2 - 10.2337/db06-1260

DO - 10.2337/db06-1260

M3 - Article

C2 - 17327429

AN - SCOPUS:33847388518

VL - 56

SP - 622

EP - 633

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -