acetyl-acetonate and Body-Weight

Oral delivery, rather than parenteral administration, would be beneficial for treating diabetic mellitus owing to the need for a long-term regimen. The objectives of this study were to evaluate oral delivery tolerance and the effects on the bone of accumulated vanadium following the long-term administration of vanadyl acetylacetonate (VAC). Normal and diabetic rats were intragastrically administered VAC at a dose of 3 mg vanadium/kg body weight once daily for 35 consecutive days. VAC did not cause any obvious signs of diarrhea, any changes in kidney or liver, or deaths in any group. The phosphate levels in the bone were slightly increased, and the calcium levels in the bone were not obviously changed as compared with those of the rat group not receiving VAC. After administration of VAC, the decreased ultimate strength, trabecular thickness, mineral apposition rate, and plasma osteocalcin in diabetic rats were either improved or normalized, but reduced bone mineral density (BMD) in diabetic rats was not improved. None of the parameters evaluated in normal rats were altered. The results indicate that the oral VAC is tolerated and benefits the diabetic osteopathy of rats, but seems not to influence the bone of normal rats. They also suggest that VAC improves diabetes-related bone disorders, primarily by improving the diabetic state.

Topics: Administration, Oral; Animals; Biomechanical Phenomena; Blood Glucose; Body Weight; Bone and Bones; Bone Density; Calcium; Diabetes Mellitus, Experimental; Hydroxybutyrates; Male; Pentanones; Phosphates; Rats; Rats, Sprague-Dawley

1. Vanadium compounds can mimic actions of insulin through alternative signalling pathways. The effects of three organic vanadium compounds were studied in non-ketotic, streptozotocin-diabetic rats: vanadyl acetylacetonate (VAc), vanadyl 3-ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM). A simple inorganic vanadium salt, vanadyl sulphate (VS) was also studied. 2. Oral administration of the three organic vanadium compounds (125 mg vanadium element 1(-1) in drinking fluids) for up to 3 months induced a faster and larger fall in glycemia (VAc being the most potent) than VS. Glucosuria and tolerance to a glucose load were improved accordingly. 3. Activities and mRNA levels of key glycolytic enzymes (glucokinase and L-type pyruvate kinase) which are suppressed in the diabetic liver, were restored by vanadium treatment. The organic forms showed greater efficacy than VS, especially VAc. 4. VAc rats exhibited the highest levels of plasma or tissue vanadium, most likely due to a greater intestinal absorption. However, VAc retained its potency when given as a single i.p. injection to diabetic rats. Moreover, there was no relationship between plasma or tissue vanadium levels and any parameters of glucose homeostasis and hepatic glucose metabolism. Thus, these data suggest that differences in potency between compounds are due to differences in their insulin-like properties. 5. There was no marked toxicity observed on hepatic or renal function. However, diarrhoea occurred in 50% of rats chronically treated with VS, but not in those receiving the organic compounds. 6. In conclusion, organic vanadium compounds, in particular VAc, correct the hyperglycemia and impaired hepatic glycolysis of diabetic rats more safely and potently than VS. This is not simply due to improved intestinal absorption, indicating more potent insulin-like properties.

Topics: Administration, Oral; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Disinfectants; Glucokinase; Glucose; Hydroxybutyrates; Hypoglycemic Agents; Injections, Intraperitoneal; Insulin; Islets of Langerhans; Ligands; Liver; Liver Glycogen; Male; Muscles; Organometallic Compounds; Pentanones; Phosphoenolpyruvate Carboxykinase (GTP); Pyrones; Pyruvate Kinase; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Vanadates; Vanadium Compounds