Amelioration of hyperglycemia and metabolic syndromes in type 2 diabetic KKA(y) mice by poly(gamma-glutamic acid)oxovanadium(IV) complex.

Abstract

Recently, we found that poly(gamma-glutamic acid)oxovanadium(IV) complex (VO(gamma-pga)) exhibits a potent antidiabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice. This result prompted us to examine its ability to treat the type 2 diabetic model KKA(y) mice with insulin resistance. We studied the in vivo antidiabetic activity of VO(gamma-pga), compared with that of vanadium(IV) oxide sulfate (VS) as control. Both compounds were orally administered at doses of 5-10 mg (0.1-0.2 mmol) V kg(-1) body mass to the KKA(y) mice for 30 days. VO(gamma-pga) normalized the hyperglycemia within 21 days, whereas VS lowered the blood glucose concentration only by a small degree. In addition, the glucose intolerance, HbA(1c) level, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia were significantly improved in VO(gamma-pga)-treated KKA(y) mice compared with those treated with VS. Based on these observations, VO(gamma-pga) is proposed to be the first orally active oxovanadium(IV)-polymer complex for the efficacious treatment of not only type 2 diabetes but also metabolic syndrome in animals.

• Authors: Subarna Karmaker, Tapan K Saha, Yutaka Yoshikawa, Hiromu Sakurai
• Journal: ChemMedChem (ChemMedChem) Vol. 2 Issue 11 Pg. 1607-12 (Nov 2007) ISSN: 1860-7187 [Electronic] Germany
• PMID: 17768733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Insulin
• Leptin
• poly(gamma-glutamic acid)
• Polyglutamic Acid
• Vanadates

Topics

• Animals
• Blood Glucose (analysis)
• Diabetes Mellitus, Experimental (complications, drug therapy)
• Glucose Tolerance Test
• Hyperglycemia (complications, drug therapy)
• Insulin (blood)
• Leptin (physiology)
• Male
• Metabolic Syndrome (complications, drug therapy)
• Mice
• Mice, Inbred C57BL
• Obesity (drug therapy)
• Polyglutamic Acid (analogs & derivatives, therapeutic use)
• Vanadates (therapeutic use)