Induction of Insulin and Islet Amyloid Polypeptide Production in Pancreatic Islet Glucagonoma Cells by Insulin Promoter Factor 1

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1996 Aug 20

PMID 8799146

Citations 27

Authors

P Serup

J Jensen

F G Andersen

M C Jorgensen

N Blume

J J Holst

O D Madsen

Affiliations

Soon will be listed here.

Abstract

Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by the lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (1994) Nature (London) 371, 606-609]. In adults, IPF1 expression is restricted to the beta-cells in the islets of Langerhans. We report here that IPF1 induces expression of a subset of beta-cell-specific genes (insulin and islet amyloid polypeptide) when ectopically expressed in clones of transformed pancreatic islet alpha-cells. In contrast, expression of IPF1 in rat embryo fibroblasts factor failed to induce insulin and islet amyloid polypeptide expression. This is most likely due to the lack of at least one other essential insulin gene transcription factor, the basic helix-loop-helix protein Beta 2/NeuroD, which is expressed in both alpha- and beta-cells. We conclude that IPF1 is a potent transcriptional activator of endogenous insulin genes in non-beta islet cells, which suggests an important role of IPF1 in beta-cell maturation.

Citing Articles

Pancreatic and duodenal homeobox-1 (PDX1) contributes to β-cell mass expansion and proliferation induced by Akt/PKB pathway.

Jara M, Werneck-de-Castro J, Lubaczeuski C, Johnson J, Bernal-Mizrachi E Islets. 2020; 12(2):32-40.

PMID: 32876522 PMC: 7527019. DOI: 10.1080/19382014.2020.1762471.

Small Molecule-Induced Pancreatic β-Like Cell Development: Mechanistic Approaches and Available Strategies.

Thakur G, Lee H, Jeon R, Lee S, Rho G Int J Mol Sci. 2020; 21(7).

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Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma.

Zhou G, Yu J, Wang A, Liu S, Sinnett-Smith J, Wu J Curr Mol Med. 2015; 16(1):83-90.

PMID: 26695692 PMC: 4994969. DOI: 10.2174/1566524016666151222145551.

Down-regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5: a novel mechanism for inhibition of cellular proliferation and insulin secretion by somatostatin.

Zhou G, Sinnett-Smith J, Liu S, Yu J, Wu J, Sanchez R Front Physiol. 2014; 5:226.

PMID: 25009500 PMC: 4069483. DOI: 10.3389/fphys.2014.00226.

New role for alpha cells as a source for new beta cells.

Watada H J Diabetes Investig. 2014; 2(1):43-4.

PMID: 24843459 PMC: 4008013. DOI: 10.1111/j.2040-1124.2010.00069.x.

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