Insulin is a potent survival factor in mesangial cells: role of the PI3-kinase/ XXXX pathway.

@entity8 @entity5732 @entity7919 @entity19 @entity1880 @entity4316 @entity2306 @entity5207 @entity13436 @entity1994 @entity4286 @entity7424 @entity4357
BACKGROUND: Elucidating the mechanisms of apoptosis is important for understanding the molecular mechanisms underlying @entity8 . The @entity4357 3 kinase (PI3-kinase)/ @entity1994 pathway is essential for survival signaling in non-renal cells. However, little is known about the anti-apoptotic effect of insulin and the role of the PI3-kinase/ @entity1994 pathway in mesangial cells (MC) apoptosis. METHODS: Apoptosis was induced in wild type, @entity7919 ( @entity7919 ) -/- and @entity5207 / @entity5207 ( @entity5207 ) -/- @entity19 MC by survival factor withdrawal, @entity4316 , ultraviolet (UV)-B irradiation and @entity1880 in the presence or absence of insulin (1 micromol/L) or insulin-like growth factor-I ( @entity7424 ; 100 ng/mL). The activation and levels of @entity1994 , @entity13436 ( @entity13436 ) and specific cell cycle proteins were determined by Western blot analysis. RESULTS: Insulin and @entity7424 inhibited wild-type MC apoptosis induced by survival factor withdrawal, @entity4316 , ultraviolet-B irradiation and @entity1880 and in @entity7919 -/- MC when apoptosis was induced by survival factor withdrawal. @entity1994 was activated by insulin and @entity7424 during apoptosis. Blocking PI3-kinase with @entity2306 reduced @entity1994 activation and abrogated the anti-apoptotic effect of insulin. @entity13436 was activated during apoptosis and blocking @entity13436 activation with @entity5732 or @entity4286 partially rescued MC from apoptosis. Moreover, insulin also suppressed @entity13436 activation during apoptosis. Our results also showed that the CDK-inhibitor @entity5207 was increased by insulin and that @entity5207 up-regulation was PI3-kinase/ @entity1994 pathway dependent. Furthermore, @entity5207 -/- MC apoptosis induced by survival factor withdrawal was not rescued by insulin in contrast to the wild-type and @entity7919 -/- MC. These data suggest that @entity5207 may have a critical role in the anti-apoptotic effect of insulin. CONCLUSIONS: Insulin is a potent survival factor for MC in response to a number of different apoptotic triggers, and this effect is mediated through the PI3-kinase/ @entity1994 pathway. Moreover, @entity13436 and @entity5207 may be involved in anti-apoptotic effect of insulin in MC.
