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Sialidase (neuraminidase, EC 3.2.1.18) catalyses the hydrolysis of terminal sialic acid residues of glyconjugates. Sialidase has been well studied in viruses and bacteria where it destroys the sialic acid-containing receptors at the surface of host cells, and mobilizes bacterial nutrients. In mammals, three types of sialidases, lysosomal, plasma membrane and cytosolic, have been described. For lysosomal sialidase in humans, the primary genetic deficiency results in an autosomal recessive disease, sialidosis, associated with tissue accumulation and urinary excretion of sialylated oligosaccharides and glycolipids. Sialidosis includes two main clinical variants: late-onset, sialidosis type I, characterized by bilateral macular cherry-red spots and myoclonus, and infantile-onset, sialidosis type II, characterized by skeletal dysplasia, mental retardation and hepatosplenomegaly. We report the identification of human lysosomal sialidase cDNA, its cloning, sequencing and expression. Examination of six sialidosis patients revealed three mutations, one frameshift insertion and two missense. We mapped the lysosomal sialidase gene to human chromosome 6 (6p21.3), which is consistent with the previous chromosomal assignment of this gene in proximity to the HLA locus.

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. Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart. Am J Physiol Endocrinol Metab 289: E30 -E39, 2005. First published February 8, 2005 doi:10.1152/ajpendo.00251.2004.-Insulin resistance in skeletal muscle and heart plays a major role in the development of type 2 diabetes and diabetic heart failure and may be causally associated with altered lipid metabolism. Hormone-sensitive lipase (HSL) is a rate-determining enzyme in the hydrolysis of triglyceride in adipocytes, and HSL-deficient mice have reduced circulating fatty acids and are resistant to diet-induced obesity. To determine the metabolic role of HSL, we examined the changes in tissue-specific insulin action and glucose metabolism in vivo during hyperinsulinemic euglycemic clamps after 3 wk of high-fat or normal chow diet in awake, HSL-deficient (HSL-KO) mice. On normal diet, HSL-KO mice showed a twofold increase in hepatic insulin action but a 40% decrease in insulin-stimulated cardiac glucose uptake compared with wild-type littermates. High-fat feeding caused a similar increase in whole body fat mass in both groups of mice. Insulin-stimulated glucose uptake was reduced by 50 -80% in skeletal muscle and heart of wild-type mice after high-fat feeding. In contrast, HSL-KO mice were protected from diet-induced insulin resistance in skeletal muscle and heart, and these effects were associated with reduced intramuscular triglyceride and fatty acyl-CoA levels in the fat-fed HSL-KO mice. Overall, these findings demonstrate the important role of HSL on skeletal muscle, heart, and liver glucose metabolism. glucose metabolism; lipid metabolism; high-fat feeding; insulin action; triglyceride INSULIN RESISTANCE PLAYS A MAJOR ROLE in the pathogenesis of type 2 diabetes and diabetes-associated cardiovascular events and may be causally associated with alteration in lipid metabolism (3,10,24,32,40,41). Adipose tissue is an important endocrine organ, capable of producing various metabolic hormones/cytokines, including resistin, adiponectin, leptin, tumor necrosis factor (TNF)-␣, and interleukin (IL)-6, and dysregulated production of adipocyte-derived cytokines has been shown to alter whole body glucose metabolism (23,25,26,49,55). Additionally, adipocytes affect glucose homeostasis by releasing fatty acids into circulation, and elevated levels of circulating fatty acids and/or lipolysis have been shown to cause insulin resistance (4, 27, 42). Our previous studies (28) demonstrated that muscle-specific and liver-specific increases in fat levels, mediated by tissue-specific overexpression of lipoprotein lipase, caused insulin resistance in skeletal muscle and liver, respectively. Additionally, mice with heart-specific overexpression of peroxisome proliferator-activated receptor (PPAR)␣ were characterized by increases in cardiac lipid oxidation and decreases in cardiac glucose metabolism (12). In contrast, Hajri et al. (19) showed that mice deficie...