PMID- 14520603
OWN - NLM
STAT- MEDLINE
DCOM- 20040713
LR  - 20211203
IS  - 0947-7349 (Print)
IS  - 0947-7349 (Linking)
VI  - 111
IP  - 6
DP  - 2003 Sep
TI  - Direct comparison of inositol phosphoglycan with prostaglandylinositol cyclic 
      phosphate, two potential mediators of insulin action.
PG  - 358-63
AB  - Though insulin signalling is thought by many groups to function without second 
      messenger action, others have provided evidence for the existence and action of 
      such regulators. Chemically quite different compounds, however, have been 
      proposed as mediators, such as various inositol phosphoglycans and 
      prostaglandylinositol cyclic phosphate (cyclic PIP). In spite of marked 
      structural differences, these compounds are reported to have the same regulatory 
      properties, i.e. to activate protein ser/thr phosphatases and to inhibit protein 
      kinase A. In order to clarify this discrepancy, the regulatory potency of these 
      different compounds was assayed under identical conditions. It was found that in 
      contrast to cyclic PIP, the synthetic inositol phosphoglycan PIG41 neither 
      directly inhibited protein kinase A nor activated protein ser/thr phosphatases. 
      However, when added to intact cells, such as primary adipocytes, PIG41 inhibited 
      isoproterenol-stimulated lipolysis. This effect most likely results from tyrosine 
      phosphorylation of insulin receptor substrates (IRSs) by PIG41. This tyrosine 
      phosphorylation is not carried out by the insulin receptor tyrosine kinase but by 
      cytosolic tyrosine kinases. This indicates that cyclic PIP, an intracellular 
      regulator, which primarily acts on protein kinase A and on protein ser/thr 
      phosphatases, operates more downstream in the signal transduction cascade as 
      compared to the inositol phosphoglycan PIG41. Thus, cyclic PIP appears to be a 
      suitable candidate to close the gap between IRSs and the protein 
      kinases/phosphatases involved in the signal transduction of insulin.
FAU - Wasner, H K
AU  - Wasner HK
AD  - Deutsches Diabetes-Forschungsinstitut, Abteilung fur klinische Biochemie und 
      Pathobiochemie, Dusseldorf, Germany. heinrich.wasner@ddfi.uni-duesseldorf.de
FAU - Muller, G
AU  - Muller G
FAU - Eckel, J
AU  - Eckel J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Exp Clin Endocrinol Diabetes
JT  - Experimental and clinical endocrinology & diabetes : official journal, German 
      Society of Endocrinology [and] German Diabetes Association
JID - 9505926
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Inositol Phosphates)
RN  - 0 (Polysaccharides)
RN  - 0 (Prostaglandins E)
RN  - 0 (inositol phosphate glycan)
RN  - 0 (prostaglandin-inositol cyclic phosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cattle
MH  - Cyclic AMP-Dependent Protein Kinases/*antagonists & inhibitors/isolation & 
      purification
MH  - Hypoglycemic Agents/pharmacology
MH  - Inositol Phosphates/*pharmacology
MH  - Kinetics
MH  - Muscle, Skeletal/enzymology
MH  - Polysaccharides/*pharmacology
MH  - Prostaglandins E/*pharmacology
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/isolation & 
      purification/metabolism
EDAT- 2003/10/02 05:00
MHDA- 2004/07/14 05:00
CRDT- 2003/10/02 05:00
PHST- 2003/10/02 05:00 [pubmed]
PHST- 2004/07/14 05:00 [medline]
PHST- 2003/10/02 05:00 [entrez]
AID - 10.1055/s-2003-42727 [doi]
PST - ppublish
SO  - Exp Clin Endocrinol Diabetes. 2003 Sep;111(6):358-63. doi: 10.1055/s-2003-42727.