Inhibition of two gluconeogenic enzymes by glycosyl-phosphatidylinositol: a model for insulin action

1994 ◽  
Vol 22 (1) ◽  
pp. 10S-10S ◽  
Author(s):  
SAM P HEYWOOD ◽  
NIGEL M. HOOPER
1988 ◽  
Vol 255 (1) ◽  
pp. C1-C11 ◽  
Author(s):  
A. R. Saltiel ◽  
P. Cuatrecasas

Despite significant advances in the past few years on the chemistry and biology of insulin and its receptor, the molecular events that couple the insulin-receptor interaction to the regulation of cellular metabolism remain uncertain. Progress in this area has been complicated by the pleiotropic nature of insulin's actions. These most likely involve a complex network of pathways resulting in the coordination of mechanistically distinct cellular effects. Because the well-recognized mechanisms of signal transduction (i.e., cyclic nucleotides, ion channels) appear not to be central to insulin action, investigators have searched for a novel second messenger system. A low-molecular-weight substance has been identified that mimics certain actions of insulin on metabolic enzymes. This substance has an inositol glycan structure and is produced by the insulin-sensitive hydrolysis of a glycosyl-phosphatidylinositol in the plasma membrane. This hydrolysis reaction, which is catalyzed by a specific phospholipase C, also results in the production of a structurally distinct diacylglycerol that may selectively regulate one or more of the protein kinases C. The glycosyl-phosphatidyl-inositol precursor for the inositol glycan enzyme modulator is structurally analogous to the recently described glycosyl-phosphatidylinositol membrane protein anchor. Preliminary studies suggest that a subset of proteins anchored in this fashion might be released from cells by a similar insulin-sensitive, phospholipase-catalyzed reaction. Efforts are underway to determine the precise role of the metabolism of glycosyl-phosphatidylinositols in insulin action.


Author(s):  
Burton B. Silver ◽  
Ronald S. Nelson

Some investigators feel that insulin does not enter cells but exerts its influence in some manner on the cell surface. Ferritin labeling of insulin and insulin antibody was used to determine if binding sites of insulin to specific target organs could be seen with electron microscopy.Alloxanized rats were considered diabetic if blood sugar levels were in excess of 300 mg %. Test reagents included ferritin, ferritin labeled insulin, and ferritin labeled insulin antibody. Target organs examined were were diaphragm, kidney, gastrocnemius, fat pad, liver and anterior pituitary. Reagents were administered through the left common carotid. Survival time was at least one hour in test animals. Tissue incubation studies were also done in normal as well as diabetic rats. Specimens were fixed in gluteraldehyde and osmium followed by staining with lead and uranium salts. Some tissues were not stained.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 36-OR
Author(s):  
LOUISE LANTIER ◽  
CURTIS C. HUGHEY ◽  
DAVID WASSERMAN

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1889-P
Author(s):  
JIA LIU ◽  
KEVIN W. AYLOR ◽  
ZHENQI LIU

Diabetes ◽  
1993 ◽  
Vol 42 (4) ◽  
pp. 514-519 ◽  
Author(s):  
M. Prochazka ◽  
S. Lillioja ◽  
J. F. Tait ◽  
W. C. Knowler ◽  
D. M. Mott ◽  
...  

Diabetes ◽  
1985 ◽  
Vol 34 (3) ◽  
pp. 241-245 ◽  
Author(s):  
G. Ward ◽  
L. C. Harrison ◽  
J. Proietto ◽  
P. Aitken ◽  
A. Nankervis

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