Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of gluconeogenesis to hyperglycemia in non-obese diabetic (NOD) mice has been investigated using oral vanadate administration. Vanadate compounds have been shown to mimic many actions of insulin; however, the exact mechanism is poorly understood. The aims of the present study were (1) to elucidate vanadate's action in vivo, and to assess the possibility that its glucose-reducing effect is dependent on the presence of a minimal concentration of insulin; and (2) to evaluate the effects of vanadate administration on the key hepatic gluconeogenesis enzymes, glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK), as well as glucose-6-phosphate dehydrogenase (G-6-PDH). Vanadate caused a significant reduction in blood glucose but failed to normalize it, despite effective serum vanadate concentrations (26.2 +/- 1.6 micromol/L). Two weeks after initiation of treatment, blood glucose levels were 26.0 +/- 1.8, 21.7 +/- 3.0, 16.0 +/- 1.6, and 14.3 +/- 2.3 mmol/L in the control (C), insulin (I), vanadate (V), and combined vanadate and insulin (V + I) groups, respectively (P < .001). G-6-Pase activity was significantly reduced by vanadate (622 +/- 134 v365 +/- 83 nmol/min/mg protein in C vV, P < .05). PEPCK activity was also significantly reduced (844 +/- 370, 623 +/- 36, 337 +/- 43, and 317 +/- 75 nmol/min/mg in the C, I, V, and V + I groups, respectively, P < .001). No significant differences in the hepatic glycogen stores and G-6-PDH activity were noted between treatment groups. Our study suggests that the inhibition of hepatic G-6-Pase and PEPCK activity by vanadate plays an important role in reducing blood glucose levels in NOD mice.
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PMID:Gluconeogenesis in non-obese diabetic (NOD) mice: in vivo effects of vandadate treatment on hepatic glucose-6-phoshatase and phosphoenolpyruvate carboxykinase. 1072 8

We have previously reported that infection with Plasmodium yoelii, Plasmodium chabaudi, or injection of extracts from malaria-parasitized red blood cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in streptozotocin (STZ)-diabetic mice. P yoelii glycosylphosphatidylinositols (GPIs) were extracted in chloroform:methanol:water (CMW) (10:10:3), purified by high-performance thin layer chromatography (HPTLC) and tested for their insulin-mimetic activities. The effects of P yoelii GPIs on blood glucose were investigated in insulin-resistant C57BL/ks-db/db diabetic mice. A single intravenous injection of GPIs (9 and 30 nmol/mouse) induced a significant dose-related decrease in blood glucose (P < .001), but insignificantly increased plasma insulin concentrations. A single oral dose of 2.7 micromol GPIs per db/db mouse significantly lowered blood glucose (P < .01). P yoelii GPIs in vitro (0.062 to 1 micromol/L) significantly stimulated lipogenesis in rat adipocytes in a dose-dependent manner both in the presence and absence of 10(-8) mol/L insulin (P < .01). P yoelii GPIs stimulated pyruvate dehydrogenase phosphatase (PDH-Pase) and inhibited both cyclic adenosine monophosphate (cAMP)-dependent protein kinase A and glucose-6-phosphatase (G6Pase). P yoelii GPIs had no effect on the activity of the gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase) and phosphoenolpyruvate carboxykinase (PEPCK). This is the first report of the hypoglycemic effect of P yoelii GPIs in murine models of type 2 diabetes. In conclusion, P yoelii GPIs demonstrated acute antidiabetic effects in db/db mice and in vitro. We suggest that P yoelii GPIs, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes.
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PMID:Improvement of glucose homeostasis in obese diabetic db/db mice given Plasmodium yoelii glycosylphosphatidylinositols. 1528 Oct 17