Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus

Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding. In addition, several studies have separately demonstrated both insulin resistance and decreases in membrane sialic acid content and associated biosynthetic enzymes in diabetes mellitus. In the present study, we investigated the role that sialic acid residues may play in insulin action and in the hepatic insulin resistance associated with nonketotic diabetes. Primary cultures of hepatocytes from normal rats treated with neuraminidase demonstrated a dose-dependent decrease in insulin-stimulated lipogenesis. At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released. Neuraminidase-releasable sialic acid was significantly decreased in hepatocytes from diabetic rats and this was associated with significant insulin resistance. Treatment of hepatocytes from diabetic rats with cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyltransferase. CMP reduced neuraminidase-releasable [14C]sialic acid incorporation into hepatocytes by 43%. The data demonstrate a role for cell surface sialic acid residues in hepatic insulin action and support a role for decreased cell surface sialic acid residues in the insulin resistance of diabetes mellitus.

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Sepsis-induced changes in in vivo insulin action in diabetic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.257.3.e301 ◽

1989 ◽

Vol 257 (3) ◽

pp. E301-E308 ◽

Cited By ~ 2

Author(s):

C. H. Lang ◽

C. Dobrescu

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Insulin Action ◽

Plasma Concentrations ◽

Diabetic Rats ◽

Hepatic Insulin Resistance ◽

Blood Levels ◽

Euglycemic Hyperinsulinemic Clamp ◽

Glucose Output

The present study examined whether sepsis exacerbates the diabetes-induced peripheral and hepatic insulin resistance. Vascular catheters were placed in diabetic (70 mg/kg streptozotocin, 4-wk duration) and nondiabetic rats, and sepsis was produced by subcutaneous injections of live Escherichia coli. Basal glucose metabolism was determined with the use of [3-3H]glucose initiated 18 h after the first injection of bacteria. Thereafter, in vivo insulin action was assessed with the use of the euglycemic hyperinsulinemic clamp technique. Sepsis in nondiabetic rats produced a 57% reduction in the maximal responsiveness for the insulin-induced increase in total glucose utilization compared with nondiabetic nonseptic animals. Diabetes alone decreased both insulin sensitivity and responsiveness. When the septic insult was superimposed on the diabetic condition, the maximum responsiveness was unchanged compared with non-septic diabetic rats, but the 50% maximally efficient dose was reduced from 817 to 190 microU/ml, suggesting an improvement in insulin sensitivity. Sepsis did not alter the insulin-induced suppression of hepatic glucose output in either nondiabetic or diabetic animals. Sepsis increased the plasma concentrations of epinephrine, norepinephrine, glucagon, and corticosterone in both nondiabetic and diabetic rats; however, the elevation in catecholamines and glucagon was 65 to 250% greater in the diabetic animals. These results indicate that hypermetabolic sepsis produces peripheral insulin resistance in nondiabetic rats but does not worsen the preexisting insulin resistance in diabetic animals, despite the higher prevailing blood levels of glucagon and catecholamines.

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Changes in cell-surface sialic acid content during chick embryo development

Mechanisms of Ageing and Development ◽

10.1016/0047-6374(83)90031-3 ◽

1983 ◽

Vol 23 (3-4) ◽

pp. 307-314 ◽

Cited By ~ 10

Author(s):

Patrice Codogno ◽

Michèle Aubery

Keyword(s):

Sialic Acid ◽

Chick Embryo ◽

Cell Surface ◽

Embryo Development ◽

Acid Content ◽

Sialic Acid Content

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Human X- and Y-bearing sperm differ in cell surface sialic acid content

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(84)91050-7 ◽

1984 ◽

Vol 124 (3) ◽

pp. 950-955 ◽

Cited By ~ 39

Author(s):

Satoru Kaneko ◽

Shigeru Oshio ◽

Toshifumi Kobayashi ◽

Rihachi Iizuka ◽

Hideo Mohri

Keyword(s):

Sialic Acid ◽

Cell Surface ◽

Acid Content ◽

Sialic Acid Content

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Sialic acid content and surface hydrophobicity of group B streptococci

Epidemiology and Infection ◽

10.1017/s0950268800050718 ◽

1993 ◽

Vol 110 (1) ◽

pp. 87-94 ◽

Cited By ~ 5

Author(s):

L. A. Teixeira ◽

A. M. S. Figueiredo ◽

B. T. Ferreira ◽

V. M. L. Alves ◽

P. E. Nagao ◽

...

Keyword(s):

Sialic Acid ◽

Cell Surface ◽

Acid Content ◽

Cell Surface Hydrophobicity ◽

Surface Hydrophobicity ◽

Gas Liquid Chromatography ◽

Group B Streptococci ◽

Sialic Acid Content ◽

Asymptomatic Patients ◽

Group B

SUMMARYThe sialic acid content and the cell-surface hydrophobicity index of 40 group B streptococci (GBS) strains were assessed. GBS isolated from invasive infections (virulent strains) presented an increased level of sialic acid content (1.4%) when compared with GBS isolated from asymptomatic patients (0.53%). Treatment of GBS strain 85634 with neuraminidase resulted in a decrease (about 25%) in the net negative surface charge as assessed by cell electrophoresis. This finding suggests that sialic acid residues are important anionogenic groups exposed on GBS cell surface.N-acetylneuraminic acid was the only sialic acid derivative characterized in the strain 85634 as evaluated by gas-liquid chromatography. GBS from different serotypes presented a hydrophobic index mean value of 0.9. Even though the sialic acid contributed effectively to the negative charge on GBS cell surface, no difference was observed in the hydrophobic index when virulent and avirulent strains were compared.

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