A. Krautheim et al., Phosphatase inhibitors induce defective hormone secretion in insulin-secreting cells and entry into apoptosis, EXP CL E D, 107(1), 1999, pp. 29-34
Citations number
26
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
A long-term (greater than or equal to 24 h) exposure of insulin-secreting H
IT T15 cells to the phosphatase inhibitor, okadaic acid (OA), at concentrat
ions inhibiting serine/threonine phosphatases 1 (PP1) and 2A (PP2A) reduced
proliferation and insulin secretion. The reduced proliferation was related
to the induction of apoptosis as evidenced by morphological criteria and t
he occurrence of internucleosomal DMA fragmentation after 15 h in 50 nM OA.
The compromised insulin secretion was not simply a consequence of a lowere
d hormone content and cell growth, but comprised also a complete suppressio
n of secretion stimulated by K+ depolarisation and forskolin. K+ depolarisa
tion of HIT cells cultured for 24 h in 50 nM OA resulted in a nearly unimpa
ired influx of Ca2+, but did not induce secretion. These observations sugge
st that the secretory defect may be localised distal to Ca2+ influx in stim
ulus secretion coupling of insulin-secreting cells.