PMID- 17164836
OWN - NLM
STAT- MEDLINE
DCOM- 20070403
LR  - 20211203
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 71
IP  - 2
DP  - 2007 Jan
TI  - IGF-1 vs insulin: respective roles in modulating sodium transport via the PI-3 
      kinase/Sgk1 pathway in a cortical collecting duct cell line.
PG  - 116-25
AB  - Insulin and insulin-like growth factor 1 (IGF-1) may play a role in the 
      regulation of sodium balance by increasing basal and aldosterone-stimulated 
      transepithelial sodium transport in the aldosterone-sensitive distal nephron 
      (ASDN). As insulin and IGF-1 are capable of binding to each other's receptor with 
      a 50- to 100-fold lower affinity than to their cognate receptor, it is not clear 
      which receptor mediates its respective sodium transport response in the ASDN. The 
      aim of the present study was to characterize the IGF-1 regulation of Na(+) 
      transport in the mCCD(cl1) cell line, a highly differentiated cell line which 
      responds to physiological concentrations (K(1/2)=0.3 nM) of aldosterone. IGF-1 
      increased basal transepithelial Na(+) transport with a K(1/2) of 0.41+/-0.07 nM. 
      Insulin dose-response curve was displaced to the right 50-fold, as compared to 
      that of IGF-1 (K(1/2)=20.0+/-3.0 nM), indicating that it acts through the IGF 
      type 1 receptor (IGF-1R). Co-stimulation with IGF-1 (0.3 nM) (or 30 nM insulin) 
      and aldosterone (0.3 nM), either simultaneously or by pretreating the cells for 5 
      h with aldosterone, induced an additive response. The phosphatidylinositol-3' 
      kinase (PI3-K) inhibitor LY294002 completely blocked IGF-1 and aldosterone 
      induced and co-induced currents. As assessed by Western blotting, protein levels 
      of the serum-, and glucocorticoid-induced kinase (Sgk1) were directly and 
      proportionally related to the current induced by either or both IGF-1 and 
      aldosterone, effects also blocked by the PI3-K inhibitor LY294002. IGF-1 could 
      play an important physiological role in regulating basal sodium transport via the 
      PI3-K/Sgk1 pathway in ASDN.
FAU - Gonzalez-Rodriguez, E
AU  - Gonzalez-Rodriguez E
AD  - Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, 
      Switzerland.
FAU - Gaeggeler, H-P
AU  - Gaeggeler HP
FAU - Rossier, B C
AU  - Rossier BC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061213
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chromones)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Insulin)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 4964P6T9RB (Aldosterone)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9NEZ333N27 (Sodium)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (serum-glucocorticoid regulated kinase)
SB  - IM
MH  - Aldosterone/pharmacology
MH  - Animals
MH  - Cell Line
MH  - Chromones/pharmacology
MH  - Immediate-Early Proteins/blood/*physiology
MH  - Insulin/*physiology
MH  - Insulin-Like Growth Factor I/*physiology
MH  - Ion Transport/drug effects
MH  - Kidney Tubules, Distal/cytology/drug effects/*physiology
MH  - Mice
MH  - Morpholines/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/blood/*physiology
MH  - Sodium/*metabolism
EDAT- 2006/12/14 09:00
MHDA- 2007/04/04 09:00
CRDT- 2006/12/14 09:00
PHST- 2006/12/14 09:00 [pubmed]
PHST- 2007/04/04 09:00 [medline]
PHST- 2006/12/14 09:00 [entrez]
AID - S0085-2538(15)52328-4 [pii]
AID - 10.1038/sj.ki.5002018 [doi]
PST - ppublish
SO  - Kidney Int. 2007 Jan;71(2):116-25. doi: 10.1038/sj.ki.5002018. Epub 2006 Dec 13.