Improvement of glucose homeostasis in obese diabetic db/db mice given Plasmodium yoelii glycosylphosphatidylinositols.
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.
| Item Type | Article |
|---|---|
| Keywords | Adipocytes/drug effects/metabolism, Animals, Blood Glucose/metabolism, Chromatography, Thin Layer, Cyclic AMP-Dependent Protein Kinases/metabolism, Diabetes Mellitus, Type 2/blood/*drug therapy/genetics, Dose-Response Relationship, Drug, Fructose-Bisphosphatase/metabolism, Glucose/*metabolism, Glucose-6-Phosphatase/metabolism, Glycosylphosphatidylinositols/*pharmacology, Homeostasis/*drug effects, *Hypoglycemic Agents, Insulin/blood, Lipids/biosynthesis, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Obese, Oxidation-Reduction, Plasmodium yoelii/*chemistry, Adipocytes, drug effects, metabolism, Animals, Blood Glucose, metabolism, Chromatography, Thin Layer, Cyclic AMP-Dependent Protein Kinases, metabolism, Diabetes Mellitus, Type 2, blood, drug therapy, genetics, Dose-Response Relationship, Drug, Fructose-Bisphosphatase, metabolism, Glucose, metabolism, Glucose-6-Phosphatase, metabolism, Glycosylphosphatidylinositols, pharmacology, Homeostasis, drug effects, Hypoglycemic Agents, Insulin, blood, Lipids, biosynthesis, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Obese, Oxidation-Reduction, Plasmodium yoelii, chemistry |
| ISI | 223314300018 |