Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus
- Univ. of Rochester Medical Center, NY (USA)
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, the authors 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{prime}-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5{prime}-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyl-transferase. CMP reduced neuraminidase-releasable ({sup 14}C)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.
- OSTI ID:
- 7007703
- Journal Information:
- American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 255:2; ISSN 0002-9513; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ACETIC ACID
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOLOGICAL EFFECTS
CARBOHYDRATES
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMISTRY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DIABETES MELLITUS
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE DISEASES
ENZYMES
FAT CELLS
HORMONES
HYDROLASES
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LIPIDS
LIVER CELLS
MAMMALS
METABOLIC DISEASES
MONOCARBOXYLIC ACIDS
MONOSACCHARIDES
NON-PEPTIDE C-N HYDROLASES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PATHOGENESIS
PEPTIDE HORMONES
PHARMACOLOGY
RADIOISOTOPES
RATS
RODENTS
SACCHARIDES
SIALIC ACID
SOMATIC CELLS
VERTEBRATES