Short-term protocols to obtain insulin-producing cells from rat adipose tissue : signaling pathways and in vivo effect

Autor: Carlos Alberto Gonçalves, Nicholas Guerini Selistre, Letícia Rodrigues, Lucas Zingano Suardi, Bárbara Carolina Federhen, Patrícia Sesterheim, Krista Minéia Wartchow
Jazyk: angličtina
Rok vydání: 2019
Předmět:
MAPK/ERK pathway
medicine.medical_treatment
Gene Expression
Adipose tissue
p38-MAPK
lcsh:Chemistry
Insulin-Secreting Cells
Insulina
exendin-4
Adipocytes
Insulin
lcsh:QH301-705.5
Adipose-derived stromal cells
Cells
Cultured
Spectroscopy
Chemistry
Cell Differentiation
General Medicine
P38-MAPK
Immunohistochemistry
Computer Science Applications
Cell biology
Phenotype
Adipose Tissue
Insulin-producing cells
Diabetic rats
diabetic rats
Signal transduction
Fosfatidilinositol 3-quinase
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
Stromal cell
Diabetes mellitus experimental
insulin-producing cells
Article
Catalysis
Diabetes Mellitus
Experimental
Inorganic Chemistry
In vivo
parasitic diseases
medicine
Animals
cardiovascular diseases
Physical and Theoretical Chemistry
Molecular Biology
PI3K/AKT/mTOR pathway
PI3K/Akt
Exenatida
Exendin-4
Organic Chemistry
Mesenchymal stem cell
Biological Transport
Mesenchymal Stem Cells
Rats
Células-tronco mesenquimais
Glucose
lcsh:Biology (General)
lcsh:QD1-999
Proteínas quinases p38 ativadas por mitógeno
adipose-derived stromal cells
Biomarkers
Zdroj: Repositório Institucional da UFRGS
Universidade Federal do Rio Grande do Sul (UFRGS)
instacron:UFRGS
International Journal of Molecular Sciences, Vol 20, Iss 10, p 2458 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 10
Popis: Studies using mesenchymal stromal cells (MSCs) as a source of insulin-secreting cells (IPCs) are a promising path in the pursuit for diabetes therapy. Here, we investigate three short-term differentiation protocols in order to generate IPCs from autologous adipose-derived stromal cells (ADSCs) with an expressive insulin-secreting profile in vitro and in vivo, as well as the signaling pathways involved in the chosen differentiation protocols. We extracted and cultured ADSCs and differentiated them into IPCs, using three different protocols with different inductors. Afterwards, the secretory profile was analyzed and IPCs differentiated in exendin-4/activin A medium, which presented the best secretory profile, was implanted in the kidney subcapsular region of diabetic rats. All protocols induced the differentiation, but media supplemented with exendin-4/activin A or resveratrol induced the expression and secretion of insulin more efficiently, and only the exendin-4/activin-A-supplemented medium generated an insulin secretion profile more like &beta
cells, in response to glucose. The PI3K/Akt pathway seems to play a negative role in IPC differentiation
however, the differentiation of ADSCs with exendin-4/activin A positively modulated the p38/MAPK pathway. Resveratrol medium activated the Jak/STAT3 pathway and generated IPCs apparently less sensitive to insulin and insulin-like receptors. Finally, the implant of IPCs with the best secretory behavior caused a decrease in hyperglycemia after one-week implantation in diabetic rats. Our data provide further information regarding the generation of IPCs from ADSCs and strengthen evidence to support the use of MSCs in regenerative medicine, specially the use of exendin-4/activin A to produce rapid and effectively IPCs with significant in vivo effects.
Databáze: OpenAIRE
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