Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It appears that different mechanisms responsible for fasting hyperbilirubinemia may be operative in different mammalian species (and subspecies). An increase in bilirubin production does not seem to occur in the horse, but a decrease in the hepatic uptake of bilirubin has been supported by a number of studies. Even though the delay in plasma elimination could also result from a decrease in hepatic blood flow, this possibility does not seem to play a major role since the hepatic uptake of compounds with low intrinsic hepatic clearance (e.g., ICG and bilirubin) appear to be affected more during fasting than those with higher clearances (e.g., BSP, bile acid, antipyrine, acetaminophen, and lidocaine) (Table I). Other possibilities such as a decrease in the affinity of hepatocellular membrane carriers involved in the uptake of these compounds or altered content of intracellular proteins involved in cellular transport or storage of bilirubin have not been investigated in horses. Competition with free fatty acids for these carrier-mediated events seems likely, particularly because horses and ponies experience high degrees of hyperlipidemia during fasting. However, studies that have explored the competition hypothesis, while not entirely negative, do not fully support it as being the sole mechanism responsible for this phenomenon. Hepatocellular UDPGT activities have not been adequately investigated in horses, but it is apparent that intraduodenal infusion of glucose is effective in reducing fasting hyperbilirubinemia and also in increasing biliary bilirubin excretion. It therefore seems possible that UDP-glucose and UDPGA levels in the livers of horses could be reduced during fasting, thus resulting in substrate depletion for the conjugating enzymes. As pointed out by Freedland et al. (1991), it is also possible that the horse, like the Bolivian squirrel monkey, might also have a relatively high apparent Km and low Vmax for UDPGT, thus resulting in high steady-state levels of plasma bilirubin, particularly during fasting. Although little is known about the cause of equine fasting hyperbilirubinemia and the subtle factors that may be modulating slight changes in the production, hepatocellular uptake, binding, conjugation, and/or biliary excretion of this pigment, it is known that it can be rapidly reversed by refeeding native hay. Perhaps one direction for future research could point toward more fully exploring what aspects of feeding are responsible for reversing this intriguing physiological phenomenon.
 ...
PMID:Equine fasting hyperbilirubinemia. 827 11

It has been proposed that the hexosamine pathway acts as a nutrient-sensing pathway, protecting the cell against abundant fuel supply, and that accumulation of hexosamines represents a biochemical mechanism by which hyperglycemia and hyperlipidemia induce insulin resistance. We hypothesized that if an increased flux through the hexosamine pathway caused insulin resistance in humans, the hexosamine levels should be increased in adipose and/or muscle tissue in insulin-resistant subjects, such as patients with type 2 diabetes and obese individuals. In addition, we reasoned that if the hexosamine pathway were a nutrient-sensing pathway, hexosamine levels in adipose and skeletal muscle tissue should be correlated with levels of circulating nutrients, such as glucose and free fatty acids (FFAs) and leptin concentrations. In a human cross-sectional study of 55 patients [20 with type 2 diabetes mellitus (DM) and 21 normal-lean (NL) and 14 normal-obese (NO) subjects] who underwent hip replacement surgery, adipose and muscle tissue biopsies were obtained and analyzed for levels of hexosamines [UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine] and hexoses (UDP-glucose and UDP-galactose). Fasting plasma glucose, glycosylated hemoglobin, serum insulin and homeostasis model assessment calculations, serum lipids, and leptin were measured on the same day. Hexosamines were not elevated in adipose and muscle tissue of patients with type 2 DM compared with NL and NO subjects (UDP-GlcNac DM vs. NL vs. NO, 3.3 +/- 2.3 vs. 2.2 +/- 2.1 vs. 3.0 +/- 2.0 nmol/g tissue in adipose tissue and 8.1 +/- 2.9 vs. 7.8 +/- 2.8 vs. 7.6 +/- 2.8 nmol/g tissue in muscle tissue, respectively). Hexosamines in adipose tissue were positively correlated with circulating levels of FFA (UDP-GlcNAc, r = 0.33, P < 0.05; UDP-N-acetylgalactosamine, r = 0.41, P < 0.01). Adipose tissue UDP-GlcNAc was correlated with leptin levels (r = 0.33; P < 0.05). No such relationship was identified in muscle tissue. In conclusion, these findings argue against a pathophysiological role of the hexosamine pathway in insulin resistance in humans but support the hypothesis that the hexosamine pathway in adipose tissue, not in muscle, is a FFA-sensing pathway and could be involved in the regulation of leptin expression.
 ...
PMID:Role of hexosamines in insulin resistance and nutrient sensing in human adipose and muscle tissue. 1547 17