Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of chronic centrally administered leptin on the glucose metabolism of streptozotocin-induced diabetic (STZ-D) rats, a model for insulin-dependent diabetes mellitus. When 3 microg.rat(-1).day(-1) of leptin was infused into the third ventricle for 6 consecutive days (STZ-LEP), STZ-D rats became completely euglycemic. The effect was not seen when the same dosage was administered s.c. Centrally administered leptin did not affect peripheral insulin levels. The feeding volume of STZ-LEP rats was suppressed to the level of non-STZ-D control rats. No improvement of hyperglycemia was noted when STZ-D rats were pair-fed to match the feeding volume of STZ-LEP rats. Thus, the euglycemia of STZ-LEP rats cannot be due to the decreased feeding volume. In the STZ-D rat, glucokinase mRNA, a marker of glycolysis, is down-regulated whereas glucose-6-phosphatase mRNA, a marker of gluconeogenesis, and glucose transporter (GLUT) 2, which is implicated in the release of glucose from liver, are up-regulated. GLUT4, uncoupling protein (UCP) 1, and UCP3 were down-regulated in brown adipose tissue. These parameters returned to normal upon central infusion of leptin. GLUT4 was not down-regulated in the skeletal muscle of STZ-D rats; however, fatty acid binding protein and carnitine palmitoyltransferase I, markers for utilization and beta-oxidation of fatty acids, were up-regulated and restored when the rats were treated with leptin. The increase and subsequent decrease of fatty acid utilization suggests a decrease of glucose uptake in the skeletal muscle of STZ-D rats, which was restored upon central leptin administration. We conclude that centrally infused leptin does not control serum glucose by regulating feeding volume or elevating peripheral insulin, but by regulating hepatic glucose production, peripheral glucose uptake, and energy expenditure. The present study indicates the possibility of future development of a new class of anti-diabetic agents that act centrally and independent of insulin action.
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PMID:Chronic central leptin infusion restores hyperglycemia independent of food intake and insulin level in streptozotocin-induced diabetic rats. 1191 53

Leucine, as an essential amino acid and activator of mTOR (mammalian target of rapamycin), promotes protein synthesis and suppresses protein catabolism. However, the effect of leucine on overall glucose and energy metabolism remains unclear, and whether leucine has beneficial effects as a long-term dietary supplement has not been examined. In the present study, we doubled dietary leucine intake via leucine-containing drinking water in mice with free excess to either a rodent chow or a high-fat diet (HFD). While it produced no major metabolic effects in chow-fed mice, increasing leucine intake resulted in up to 32% reduction of weight gain (P < 0.05) and a 25% decrease in adiposity (P < 0.01) in HFD-fed mice. The reduction of adiposity resulted from increased resting energy expenditure associated with increased expression of uncoupling protein 3 in brown and white adipose tissues and in skeletal muscle, while food intake was not decreased. Increasing leucine intake also prevented HFD-induced hyperglycemia, which was associated with improved insulin sensitivity, decreased plasma concentrations of glucagon and glucogenic amino acids, and downregulation of hepatic glucose-6-phosphatase. Additionally, plasma levels of total and LDL cholesterol were decreased by 27% (P < 0.001) and 53% (P < 0.001), respectively, in leucine supplemented HFD-fed mice compared with the control mice fed the same diet. The reduction in cholesterol levels was largely independent of leucine-induced changes in adiposity. In conclusion, increases in dietary leucine intake substantially decrease diet-induced obesity, hyperglycemia, and hypercholesterolemia in mice with ad libitum consumption of HFD likely via multiple mechanisms.
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PMID:Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. 1736 Sep 78