Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum mannose concentration increases in diabetic patients and correlates closely with blood glucose. In patients with glomerulonephritis, serum mannose and mannose/glucose ratio positively correlate with dyslipidemia and the extent of urinary protein excretion. We investigated whether changes in serum mannose mark subjects with features of metabolic syndrome, including obesity, hypertension, glucose intolerance, and dyslipidemia. The study comprised 20 patients with mean age of 68 (SD 11) years, body mass index 27.2 (SD 5.1) kg/m2, blood glucose 6.2 (SD 1.6) mmol/L, serum total cholesterol 6.3 (SD 1.2) mmol/L, triglyceride 2.0 (SD 0.08) mmol/L, uric acid 320 (SD 109) micromol/L, mannose 60.0 (SD 17) micromol/L, and mannose/glucose ratio 9.7 (SD 1.8) micromol/mmol. Serum mannose correlated with blood glucose (r=0.758, p=0.012), triglyceride (r=0.478, p=0.023), and HDL-cholesterol (r = approximately 0.427, p=0.022). Mannose/glucose ratio correlated with BMI (r=0.581, p=0.033), mannose (r=0.491, p=0.035), and uric acid (r=0.608, p=0.027). The rate of VLDL lipoprotein turnover may be instrumental in the regulation of serum mannose concentration. We conclude that an altered mannose metabolism is a novel consideration among the metabolic abnormalities in the metabolic syndrome.
 ...
PMID:Metabolic syndrome is associated with changes in D-mannose metabolism. 1069 Oct 51

Glucose uptake into adipose and liver cells is known to up-regulate mRNA levels for various lipogenic enzymes such as fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). To determine whether the hexosamine biosynthesis pathway (HBP) mediates glucose regulation of mRNA expression, we treated primary cultured adipocytes for 18 h with insulin (25 ng/ml) and either glucose (20 mm) or glucosamine (2 mm). A ribonuclease protection assay was used to quantitate mRNA levels for FAS, ACC, and glycerol-3-P dehydrogenase (GPDH). Treatment with insulin and various concentrations of d-glucose increased mRNA levels for FAS (280%), ACC (93%), and GPDH (633%) in a dose-dependent manner (ED50 8-16 mm). Mannose similarly elevated mRNA levels, but galactose and fructose were only partially effective. l-glucose had no effect. Omission of glutamine from the culture medium markedly diminished the stimulatory effect of glucose on mRNA expression. Since glutamine is a crucial amide donor in hexosamine biosynthesis, we interpret these data to mean that glucose flux through the HBP is linked to regulation of lipogenesis through control of gene expression. Further evidence for hexosamine regulation was obtained using glucosamine, which is readily transported into adipocytes where it directly enters the HBP. Glucosamine was 15-30 times more potent than glucose in elevating FAS, ACC, and GPDH mRNA levels (ED50 approximately 0.5 mm). In summary: 1) GPDH, FAS, and ACC mRNA levels are upregulated by glucose; 2) glucose-induced up-regulation requires glutamine; and 3) mRNA levels for lipogenic enzymes are up-regulated by glucosamine. Hyperglycemia is the hallmark of diabetes mellitus and leads to insulin resistance, impaired glucose metabolism, and dyslipidemia. We postulate that disease pathophysiology may have a common underlying factor, excessive glucose flux through the HBP.
 ...
PMID:Role of hexosamine biosynthesis in glucose-mediated up-regulation of lipogenic enzyme mRNA levels: effects of glucose, glutamine, and glucosamine on glycerophosphate dehydrogenase, fatty acid synthase, and acetyl-CoA carboxylase mRNA levels. 1275 50