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Isolated Pancreatic Islet Treatment and Apoptosis Measurement
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Small molecules exert anti-apoptotic effect and reduce oxidative stress augmenting insulin secretion in stem cells

Bhawna Chandravanshi1, Ramesh Bhonde1

  • 1School of Regenerative Medicine, Manipal University, GKVK Post, Bellary Road, Allalasandra, Yelahanka, 560065 Bangalore, India.

European Journal of Pharmacology
|September 11, 2016
PubMed

Insights

Small molecules like EPA, DHA, metformin, and GABA protect engineered pancreatic islet-like cell aggregates (ICAs) from hypoxia-induced cell death. These compounds enhance ICA survival and function, crucial for diabetes transplantation success.

Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Endocrinology

Background:

  • Pancreatic islet transplantation is a key treatment for Type 1 diabetes.
  • Hypoxia-induced cell death significantly hinders the success of islet transplantation.
  • Islet-like cell aggregates (ICAs) offer a potential alternative for cell-based therapies.

Purpose of the Study:

  • To investigate the protective role of small molecules against hypoxia in engineered ICAs.
  • To evaluate the impact of specific small molecule combinations on ICA viability and function under oxygen deprivation.
  • To explore the underlying molecular mechanisms, including hypoxia-inducible factor 1α (HIF1α) and apoptotic pathways.

Main Methods:

  • Engineered ICAs from umbilical cord matrix were exposed to hypoxic conditions (<5% O2).
  • Cell death was assessed using FDA/PI staining, Caspase 3 activity, and reactive oxygen species (ROS) levels.
  • HIF1α expression (transcriptional and translational) and antioxidant enzyme activity (GPx) were analyzed.

Main Results:

  • Small molecules, particularly combinations of EPA, DHA with metformin or GABA, significantly improved ICA viability and insulin secretion under hypoxia.
  • These combinations demonstrated anti-apoptotic effects by reducing Caspase 3 activity, ROS, and malonaldehyde (MDA) levels.
  • Enhanced glutathione peroxidase (GPx) activity and increased HIF1α expression at both gene and protein levels were observed.

Conclusions:

  • Small molecules effectively protect engineered ICAs from hypoxic damage, preserving their viability and function.
  • The protective mechanism involves up-regulation of HIF1α and down-regulation of Caspase 3 activity.
  • These findings support the potential of small molecule preconditioning for improving islet transplantation outcomes in Type 1 diabetes.
Keywords:
Docosahexaenoic acid (DHA)Eicosapentaenoic acid (EPA)HypoxiaIslet like cell aggregates (ICA's)Metforminγ amino butyric acid (GABA)

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