Expression of secretory phospholipase A₂in insulitis of human transplanted pancreas and its insulinotropic effect on isolated rat islets

Abstract

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.

Plasma Metabolomics Reveal Alterations of Sphingo- and Glycerophospholipid Levels in Non-Diabetic Carriers of the Transcription Factor 7-Like 2 Polymorphism rs7903146

“…In contrast to these results, other studies demonstrated that lysoPCs stimulate glucose uptake in 3T3-L1 adipocytes by elevating glucose transporter type 4 levels at the plasma membrane yielding to lower blood glucose levels in normal and diabetic mice [45]. Treatment of cultured islet cells with phospholipase increased lysoPC contents and insulin secretion [46]. Thus, there may be positive and negative effects of some lysoPC species on insulin resistance and β-cell function.…”

Group X Secretory Phospholipase A2 Regulates Insulin Secretion through a Cyclooxygenase-2-dependent Mechanism

“…Of the 10 members of the sPLA 2 family known to be expressed by mammalian cells, to date only group IB and group IIA sPLA 2 have been shown to be expressed in rodent pancreatic islets (36,37). However, group IB sPLA 2 deficiency does not lead to alterations in basal or glucose-stimulated insulin secretion in mice (38) and group IIA sPLA 2 is naturally deficient in the inbred C57BL/6 mouse strain (39), ruling out a role for these two isozymes in the current study.…”

Cytosolic and Calcium-Independent Phospholipases A2 Activation and Prostaglandins E2 Are Associated with Escherichia coli-Induced Reduction of Insulin Secretion in INS-1E Cells

“…It has been shown that iPLA 2 ß is involved in apoptosis of ß-cells of the pancreas during diabetes and its inhibition is able to reduce apoptosis, thus preventing cell dysfunction associated with diabetes [ 31 ]. Type IB sPLA 2 is contained in insulin secretory granules of pancreatic islet ß-cells, it is co-secreted with insulin from glucose-stimulated islets [ 32 ] and it is expressed in human islets of transplanted pancreas after the recurrence of type 1 diabetes mellitus with insulitis [ 33 ].…”