Vanadyl-biguanide complexes as potential synergistic insulin mimics
L C Woo1, V G Yuen, K H Thompson
1Department of Chemistry, University of British Columbia, Vancouver, Canada.
Journal of Inorganic Biochemistry
|December 22, 1999
Summary
New oxovanadium(IV) coordination compounds with biguanides, like metformin, were synthesized. While showing blood-glucose-lowering effects in diabetic rats, the biguanide component did not enhance insulin activity.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Pharmacology
Background:
- Vanadium compounds exhibit blood-glucose-lowering properties.
- Biguanides, such as metformin, are established oral hypoglycemic agents for type 2 diabetes mellitus.
- Synergistic effects in coordination compounds may enhance therapeutic potential.
Purpose of the Study:
- To synthesize and characterize novel oxovanadium(IV) coordination complexes with biguanides.
- To evaluate the insulin-enhancing and blood-glucose-lowering potential of these complexes.
- To investigate potential synergistic effects between oxovanadium(IV) and biguanide ligands.
Main Methods:
- Synthesis of bis(biguanidato)oxovanadium(IV) complexes: [VO(big)2], [VO(metf)2], and [VO(phenf)2].
- Characterization using infrared spectroscopy, mass spectrometry, elemental analyses, magnetic susceptibility, and 1H NMR.
- In vivo testing in streptozotocin-diabetic rats, assessing blood-glucose levels after intraperitoneal and oral administration of VO(metf)2.
Main Results:
- Novel, air-stable oxovanadium(IV) biguanide complexes were successfully prepared.
- VO(metf)2 demonstrated significant blood-glucose lowering in STZ-diabetic rats via both i.p. and p.o. routes.
- No synergistic insulin-enhancing effects were observed from the inclusion of the biguanide ligand.
Conclusions:
- Oxovanadium(IV) biguanide complexes retain blood-glucose-lowering activity.
- The biguanide ligand does not appear to confer additional insulin-enhancing benefits in these specific coordination compounds.
- Further research into vanadium-based antidiabetic agents is warranted.
Related Concept Videos
01:17Oral Hypoglycemic Agents: Sulfonylureas
Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide (Glucotrol),...
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood glucose levels...
01:06Oral Hypoglycemic Agents: Glinides
Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively manages...
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are typically...
Acarbose and miglitol are typically...
01:24Glucagon-like Receptor Agonists
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
01:23Dipeptidyl Peptidase 4 Inhibitors
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...