i(3)so3-galactosylceramide and Insulin-Resistance

The glycosphingolipid beta-galactosylceramide-3-O-sulfate (sulfatide) is present in the secretory granules of the insulin producing beta-cells and may act as a molecular chaperone of insulin. The final step in sulfatide synthesis is performed by cerebroside sulfotransferase (CST) (EC 2.8.2.11). The aim of this study was to investigate whether two single nucleotide polymorphisms (SNP), rs2267161 located in an exon or rs42929 located in an intron, in the gene encoding CST are linked to type 2 diabetes (T2D).. As a population survey, 265 male and female patients suffering from T2D and 291 gender matched controls were examined.. A higher proportion of T2D patients were heterozygous at SNP rs2267161 with both T (methionine) and C (valine) alleles present (49.8% versus 41.3%, P = .04). The calculated odd risk for T2D was 1.47 (1.01-2.15, P = .047). Among female controls, the homozygous CC individuals displayed lower insulin resistance measured by HOMA-IR (P = .05) than the C/T or TT persons; this was particularly prevalent in individuals who exercise (P = .03).. Heterozygosity at SNP rs2267161 in the gene encoding the CST enzyme confers increased risk of T2D. Females with the CC allele showed lower insulin resistance.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Exercise; Female; Gene Frequency; Genetic Predisposition to Disease; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Polymorphism, Single Nucleotide; Sulfoglycosphingolipids; Sulfotransferases; Surveys and Questionnaires; Sweden

The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes.. A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey.. Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently).. We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.

Topics: Antigens, CD; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Galactosylceramides; Humans; Insulin Resistance; Lactosylceramides; Male; Middle Aged; Population Surveillance; Risk Factors; Sex Distribution; Sulfoglycosphingolipids; Sweden