Int J Stem Cells.  2017 Nov;10(2):154-159. 10.15283/ijsc17033.

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

• Pfützner
• Schipper D
• Pansky A
• Kleinfeld
• Roitzheim
• Tobiasch E

• KMID: 2400869
• DOI: http://doi.org/10.15283/ijsc17033

Abstract

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.

Keyword

Intact proinsulin; β-cell dysfunction; Visceral lipid tissue; Adipogenic effect; Stem cell differentiation

MeSH Terms

Adipocytes*
Adiponectin
Body Weight
Cell Culture Techniques
Cell Differentiation
Humans
In Vitro Techniques*
Insulin*
Lipectomy
Mesenchymal Stromal Cells*
Proinsulin*
Adiponectin
Insulin
Proinsulin

Figure

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  Fig. 1 Differentiation of adipose-tissue derived mesenchymal stem cells into adipocytes as seen microscopically and confirmed by Oil-Red-Staining.

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  Fig. 2 The adiponectin secretion from differentiating mesenchymal stem cells cultivated with insulin and proinsulin in vitro confirms that the lipogenic effect of proinsulin is equipotent to the lipogenic action of insulin. ***p<0.001.

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  Fig. 3 Schematic presentation of the contribution of proinsulin to the overall impairment of the metabolic situation in case of severe β-cell dysfunction.

Reference

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