Universität zu Köln

Horn, Signe, Kirkegaard, Jeannette S., Hoelper, Soraya, Seymour, Philip A., Rescan, Claude, Nielsen, Jens H., Madsen, Ole D., Jensen, Jan N., Kruger, Marcus, Gronborg, Mads and Ahnfelt-Ronne, Jonas (2016). Research Resource: A Dual Proteomic Approach Identifies Regulated Islet Proteins During beta-Cell Mass Expansion In Vivo. Mol. Endocrinol., 30 (1). S. 133 - 144. CARY: OXFORD UNIV PRESS INC. ISSN 1944-9917

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Abstract

Diabetes is characterized by insulin insufficiency due to a relative paucity of functional beta-cell mass. Thus, strategies for increasing beta-cell mass in situ are sought-after for therapeutic purposes. Pregnancy is a physiological state capable of inducing robust beta-cell mass expansion, however, the mechanisms driving this expansion are not fully understood. Thus, the aim of this study was to characterize pregnancy-induced changes in the islet proteome at the peak of beta-cell proliferation in mice. Islets from pregnant and nonpregnant littermates were compared via 2 proteomic strategies. In vivo pulsed stable isotope labeling of amino acids in cell culture was used to monitor de novo protein synthesis during the first 14.5 days of pregnancy. In parallel, protein abundance was determined using ex vivo dimethyl labelling at gestational day 14.5. Comparison of the 2 datasets revealed 170 islet proteins to be up regulated as a response to pregnancy. These included several proteins, not previously associated with pregnancy-induced islet expansion, such as CLIC1, STMN1, MCM6, PPIB, NEDD4, and HLTF. Confirming the validity of our approach, we also identified proteins encoded by genes known to be associated with pregnancy-induced islet expansion, such as CHGB, IGFBP5, MATN2, EHHADH, IVD, and BMP1. Bioinformatic analyses demonstrated enrichment and activation of the biological functions: protein synthesis and proliferation, and predicted the transcription factors HNF4 alpha, MYC, MYCN, E2F1, NFE2L2, and HNF1 alpha as upstream regulators of the observed expressional changes. As the first characterization of the islet-proteome during pregnancy, this study provides novel insight into the mechanisms involved in promoting pregnancy-induced beta-cell mass expansion and function.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Horn, Signe UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirkegaard, Jeannette S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoelper, Soraya UNSPECIFIED UNSPECIFIED UNSPECIFIED Seymour, Philip A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rescan, Claude UNSPECIFIED UNSPECIFIED UNSPECIFIED Nielsen, Jens H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Madsen, Ole D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jensen, Jan N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kruger, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Gronborg, Mads UNSPECIFIED UNSPECIFIED UNSPECIFIED Ahnfelt-Ronne, Jonas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-293070
DOI:	10.1210/me.2015-1208
Journal or Publication Title:	Mol. Endocrinol.
Volume:	30
Number:	1
Page Range:	S. 133 - 144
Date:	2016
Publisher:	OXFORD UNIV PRESS INC
Place of Publication:	CARY
ISSN:	1944-9917
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INSULIN-SECRETION; GENE-EXPRESSION; PROLACTIN RECEPTOR; PANCREATIC-ISLETS; CYCLOPHILIN-B; PREGNANCY; GROWTH; MOUSE; PROLIFERATION; RNA Multiple languages Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29307