Expression of secretory phospholipase A 2 in insulitis of human transplanted pancreas and its insulinotropic effect on isolated rat islets

• Published in: Islets 2010-09, Vol.2 (5), p.274-277
• Main Authors: Ishida-Oku, Miwako, Iwase, Masanori, Sonoki, Kazuo, Sasaki, Nobuhiro, Imoto, Hirofumi, Uchizono, Yuji
• Format: Article
• Language: English
• Subjects: Animals; Biopsy; Calcium Signaling - drug effects; Carbamates - pharmacology; Crotalid Venoms - enzymology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - therapy; Enzyme Inhibitors - pharmacology; Group II Phospholipases A2 - metabolism; Humans; Indolizines - pharmacology; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Lysophosphatidylcholines - metabolism; Male; Organ Culture Techniques; Pancreas - enzymology; Pancreas - metabolism; Pancreas - pathology; Pancreas Transplantation - adverse effects; Pancreas Transplantation - pathology; Phospholipases A2, Secretory - antagonists & inhibitors; Phospholipases A2, Secretory - pharmacology; Rats; Rats, Sprague-Dawley; Recurrence
• ISSN: 1938-2014; 1938-2022
• DOI: 10.4161/isl.2.5.12728

The expression of secretory phospholipase A 2 (sPLA 2) is induced by inflammatory stimuli in various cells, and sPLA 2 contribute to produce proinflammatory lipid mediators via hydrolyzing plasma membrane phospholipids into free fatty acid and lysophospholipid. We studied the expression of group IIA sPLA 2 in human islets of transplanted pancreas before and after the recurrence of type 1 diabetes mellitus in a case study. In addition, the effects of exogenous sPLA 2 in isolated rat islets were investigated. Expression of group IIA sPLAs was immunohistochemicaly investigated in the pancreas graft biopsy specimens. Insulin secretion was evaluated by static incubation with different concentrations of snake venom sPLA 2. Intracellular free Ca ( 2) + concentration was measured with Fura 2 and lysophosphatidylcholine (LPC) contents in islets were determined by electrospray ionization-liquid chromatography/mass spectrometry. Group IIA sPLA 2 was not expressed in islets without insulitis before the recurrence, whereas it was diffusely expressed in islets after the recurrence with insulitis. There were cells co-expressing group IIA sPLA 2 and insulin. sPLA 2 dose-dependently induced insulin secretion in isolated rat islets, which was completely prevented by a specific sPLA 2 inhibitor indoxam. The application of sPLA 2 did not affect intracellular free Ca ( 2) + concentration in β cells. On the other hand, LPC contents in islets were significantly increased in sPLA 2-treated islets compared with untreated islets. Incubation with indoxam suppressed the sPLA 2-induced increase of LPC. In conclusion, the present study suggests that group IIA sPLA 2 may be expressed in islets during insulitis in humans. Although sPLA 2 induced insulin secretion in vitro probably via the production of lysophospholipid, the significance of this enzyme expression in insulitis remains elusive.