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Mesenchymal Stem Cell Differentiation into Adipocytes Is Equally Induced by Insulin and Proinsulin In Vitro

  • Background and Objectives: In advanced β-cell dysfunction, proinsulin is increasingly replacing insulin as major component of the secretion product. It has been speculated that proinsulin has at least the same adipogenic potency than insulin, leading to an increased tendency of lipid tissue formation in patients with late stage β-cell dysfunction. Methods and Results: Mesenchymal stem cells obtained from liposuction material were grown in differentiation media containing insulin (0.01 μmol), proinsulin (0.01 μmol) or insulin+proinsulin (each 0.005 μmol). Cell culture supernatants were taken from these experiments and an untreated control at weeks 1, 2, and 3, and were stored at -80°C until analysis. Cell differentiation was microscopically supervised and adiponectin concentrations were measured as marker for differentiation into mature lipid cells. This experiment was repeated three times. No growth of lipid cells and no change in adiponectin values was observed in the negative control group (after 7/14/12 days: 3.2±0.5/3.3±0.1/4.4±0.5 ng/ml/12 h). A continuous differentiation into mature adipocytes (also confirmed by Red-Oil-staining) and a corresponding increase in adiponectin values was observed in the experiments with insulin (3.6±1.9/5.1±1.4/13.3±1.5 ng/ml/12 h; p<0.05 week 1 vs. week 3) and proinsulin (3.3±1.2/3.5±0.3/12.2±1.2 ng/ml/12 h; p<0.05). Comparable effects were seen with the insulin/proinsulin combination. Conclusions: Proinsulin has the same adipogenic potential than insulin in vitro. Proinsulin has only 10∼20% of the glucose-lowering effect of insulin. It can be speculated that the adipogenic potential of proinsulin may be a large contributor to the increased body weight problems in patients with type 2 diabetes and advanced β-cell dysfunction.

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Document Type:Article
Author:Andreas Pfützner, Dorothee Schipper, Andreas Pansky, Claudia Kleinfeld, Barbara Roitzheim, Edda Tobiasch
Parent Title (English):International Journal of Stem Cells
First Page:154
Last Page:159
Publisher:Korean Society for Stem Cell Research
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2017/11/30
Copyright:Copyright ⓒ 2017 by the Korean Society for Stem Cells Research. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License.
Keyword:Adipogenic effect; Intact proinsulin; Stem cell differentiation; Visceral lipid tissue; β-cell dysfunction
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Projects:IngenieurNachwuchs 2015: PersoImplant - Personalisierte zellbesiedelte Implantate für Knochendefekte mit 'kritischer Größe' (DE/BMBF/03FH019IX5,13FH019IX5)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Entry in this database:2017/12/15
Licence (German):License LogoCreative Commons - CC BY-NC - Namensnennung - Nicht kommerziell 4.0 International