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Updated: Sep 4, 2025

Isolated Pancreatic Islet Treatment and Apoptosis Measurement
Published on: May 2, 2025
Perilipin 2 Protects against Lipotoxicity-Induced Islet Fibrosis by Inducing Islet Stellate Cell Activation Phenotype
Yunting Zhou1, Yuming Wang1, Chengming Ni2
1Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Aims:
We explored whether and how perilipin 2 (Plin2) protected islets against lipotoxicity-induced islet dysfunction by regulating islet stellate cells (ISCs) activation.
Methods:
Six-week-old male rats were given a high-fat diet or a control diet for 28 weeks. Glucose metabolic phenotypes were assessed using glucose/insulin tolerance tests, masson, and immunohistochemical staining. ISCs activation levels were assessed from rats and palmitic acid- (PA-) treated cultured ISCs by immunofluorescence, Oil red O staining, electron microscopy, quantitative PCR, and western blotting. Changes in ISCs phenotype of activation degree and its underlying mechanisms were assessed by target gene lentiviral infection, high-performance liquid chromatography (HPLC), and western blotting.
Results:
Obese rats showed glucose intolerance, decreased endocrine hormone profiles, and elevated expression of α-smooth muscle actin (α-SMA), a polygonal appearance without cytoplasmic lipid droplets of ISCs in rats and isolated islets. PA-treated cultured ISCs exhibited faster proliferation and migration abilities with the induction of mRNA levels of lipid metabolism proteins, especially Plin2. The overexpression of Plin2 resulted in ISCs "re-quiescent" phenotypes associated with inhibition of the Smad3-TGF-β signaling pathways.
Conclusions:
Our observations suggest a protective role of Plin2 in weakening ISCs activation. It may serve as a novel therapeutic target for preventing islet fibrosis for T2DM.
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