In this study we examine the hypothesis that an inositol glycan phosphate can act similarly to insulin on intact cells. The inositol glycan phosphate used in this study (glycan α) was isolated previously from the glycoinositol phospholipid anchor of human erythrocyte acetylcholinesterase and was shown to have the structure glycine-ethanolamine-PO4-Man-Man-(N,N-dimethylethanolamine-PO4)Man- (N,N-dimethyl)GlcN-inositol-PO4. The cellular response investigated was the glucagon-stimulated activation of glycogen phosphorylase in rat hepatocytes. When hepatocytes were incubated with 20 nM glucagon for 4 min, the ratio of phosphorylase a activity to total phosphorylase increased from a basal value of 0.49 ± 0.02 to 0.82 ± 0.03 (mean ± SE, n = 15). Inclusion of either 100 nM insulin or 3–10 μM glycan α during the glucagon incubation significantly decreased the glucagon-stimulated activity ratio to 0.74 ± 0.03 for either agent. Furthermore, hepatocyte preparations differed in their response to insulin and were divided into insulin-responsive and -resistant groups. Glycan α had a significant effect only in the insulin-responsive group for which the observed activity ratio for 10 microM glycan α plus glucagon (0.68 ± 0.05) compared closely with that for insulin plus glucagon (0.70 ± 0.04). For the insulin-resistant group, the activity ratio in the presence of 10 μM glycan α was 0.81 ± 0.03, unchanged from the control with glucagon alone. Because glycan α contains an inositol phosphate group, the effect of inositol cyclic 1,2-phosphate on the glucagon-stimulated activity ratio was determined. Inositol cyclic 1,2-phosphate at 1–10 μM significantly decreased the activity ratio to the same extent as insulin in seven insulin-responsive preparations. Glycan a and inositol cyclic 1,2-phosphate differed from insulin in eliciting no decrease in the 8-bromoadenosine cyclic 3′-5′-monophosphatestimulated phosphorylase activity ratio in hepatocytes. The results indicate that glycan α and inositol cyclic 1,2-phosphate can mimic some effects of insulin on intact hepatocytes.
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Original Articles|
September 01 1993
Inositol Glycan Phosphate Derived from Human Erythrocyte Acetylcholinesterase Glycolipid Anchor and Inositol Cyclic 1,2-Phosphate Antagonize Glucagon Activation of Glycogen Phosphorylase
Mark A Deeg;
Mark A Deeg
Departments of Pharmacology and Medicine, School of Medicine, Case Western Reserve University
Cleveland, Ohio
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Eric P Brass;
Eric P Brass
Departments of Pharmacology and Medicine, School of Medicine, Case Western Reserve University
Cleveland, Ohio
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Terrone L Rosenberry
Terrone L Rosenberry
Departments of Pharmacology and Medicine, School of Medicine, Case Western Reserve University
Cleveland, Ohio
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Address correspondence and reprint requests to Dr. Terrone L. Rosenberry, Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106–4965.
Diabetes 1993;42(9):1318–1323
Article history
Received:
January 12 1993
Revision Received:
April 29 1993
Accepted:
April 29 1993
PubMed:
8349043
Citation
Mark A Deeg, Eric P Brass, Terrone L Rosenberry; Inositol Glycan Phosphate Derived from Human Erythrocyte Acetylcholinesterase Glycolipid Anchor and Inositol Cyclic 1,2-Phosphate Antagonize Glucagon Activation of Glycogen Phosphorylase. Diabetes 1 September 1993; 42 (9): 1318–1323. https://doi.org/10.2337/diab.42.9.1318
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