OR 72: Amino acid conjugated small molecule BLX-1002 lowers blood glucose in insulin resistant db/db and ob/ob mice and inhibits TNF-α , IL-6 cytokines
BLX-1002 is a water-soluble, orally active, modified single amino acid derivative with no structural resemblance with any existing compounds. When given orally in obese diabetic db/db orob/ob mice, at a dose of 50 mg/kg body weight per day, it was able to reduce blood glucose by 30-40% compare to ve...
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| Veröffentlicht in: | American journal of hypertension 2004-05, Vol.17 (S1), p.32A-32A |
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| container_end_page | 32A |
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| container_issue | S1 |
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| container_title | American journal of hypertension |
| container_volume | 17 |
| creator | Dey, Deben Pandey, Bindu Nag, Abhijeet Peng, Ivan Chovatia, Mansi Neogi, Partha Nag, Bishwajit |
| description | BLX-1002 is a water-soluble, orally active, modified single amino acid derivative with no structural resemblance with any existing compounds. When given orally in obese diabetic db/db orob/ob mice, at a dose of 50 mg/kg body weight per day, it was able to reduce blood glucose by 30-40% compare to vehicle treated animals. Unlike other drugs, it reduced body weight gains in these animal models without any effect in food intake. BLX-1002 significantly lowered blood glycosylated hemoglobin ( 0.8%), free fatty acid (43%), triglyceride (20%) and total cholesterol (28%) levels compare to control group. In high fat diet model, BLX-1002 reduced body weight gain and significantly (p |
| doi_str_mv | 10.1016/j.amjhyper.2004.03.071 |
| format | Article |
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When given orally in obese diabetic db/db orob/ob mice, at a dose of 50 mg/kg body weight per day, it was able to reduce blood glucose by 30-40% compare to vehicle treated animals. Unlike other drugs, it reduced body weight gains in these animal models without any effect in food intake. BLX-1002 significantly lowered blood glycosylated hemoglobin ( 0.8%), free fatty acid (43%), triglyceride (20%) and total cholesterol (28%) levels compare to control group. In high fat diet model, BLX-1002 reduced body weight gain and significantly (p<0.05) improved oral glucose tolerance. BLX-1002 does not induce adipogenesis, aP2 (fatty acid binding protein) or Acrp30 (adiponectin) expression in 3T3-L1 adipocytes or human pre-adipocytes and most probably it is not an agonist of PPARγ. BLX-1002 strongly inhibits lipopolysacharide (LPS) induced pro-inflammatory cytokines like IL-6 and TNFα production in both human monocytes and in animals. BLX-1002 rapidly induces 14C-Deoxyglucose uptake in isolated rat adipocytes, which was blocked by PI 3 kinase inhibitor LY294002. Similar to insulin, it also blocked isoproterenol induced lipolysis in both rat and human adipocytes. In Chinese hamster ovary cells, which over express the human insulin receptor (CHO.IR), BLX-1002 induces tyrosine phosphorylation of IRβ and insulin receptor substrate-1 (IRS-1) similar to insulin. In streptozotocin induced diabetes model in mice, it lowered blood glucose and triglyceride levels compare to controls. A repeat dose 28 days chronic toxicological studies in rats and dogs did not show any increase of liver enzymes (AST or ALT), BUN and creatinine levels. These results combined demonstrate the potential of BLX-1002 as a novel compound for the treatment of Type-II diabetes and related disorders. 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When given orally in obese diabetic db/db orob/ob mice, at a dose of 50 mg/kg body weight per day, it was able to reduce blood glucose by 30-40% compare to vehicle treated animals. Unlike other drugs, it reduced body weight gains in these animal models without any effect in food intake. BLX-1002 significantly lowered blood glycosylated hemoglobin ( 0.8%), free fatty acid (43%), triglyceride (20%) and total cholesterol (28%) levels compare to control group. In high fat diet model, BLX-1002 reduced body weight gain and significantly (p<0.05) improved oral glucose tolerance. BLX-1002 does not induce adipogenesis, aP2 (fatty acid binding protein) or Acrp30 (adiponectin) expression in 3T3-L1 adipocytes or human pre-adipocytes and most probably it is not an agonist of PPARγ. BLX-1002 strongly inhibits lipopolysacharide (LPS) induced pro-inflammatory cytokines like IL-6 and TNFα production in both human monocytes and in animals. BLX-1002 rapidly induces 14C-Deoxyglucose uptake in isolated rat adipocytes, which was blocked by PI 3 kinase inhibitor LY294002. Similar to insulin, it also blocked isoproterenol induced lipolysis in both rat and human adipocytes. In Chinese hamster ovary cells, which over express the human insulin receptor (CHO.IR), BLX-1002 induces tyrosine phosphorylation of IRβ and insulin receptor substrate-1 (IRS-1) similar to insulin. In streptozotocin induced diabetes model in mice, it lowered blood glucose and triglyceride levels compare to controls. A repeat dose 28 days chronic toxicological studies in rats and dogs did not show any increase of liver enzymes (AST or ALT), BUN and creatinine levels. These results combined demonstrate the potential of BLX-1002 as a novel compound for the treatment of Type-II diabetes and related disorders. 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When given orally in obese diabetic db/db orob/ob mice, at a dose of 50 mg/kg body weight per day, it was able to reduce blood glucose by 30-40% compare to vehicle treated animals. Unlike other drugs, it reduced body weight gains in these animal models without any effect in food intake. BLX-1002 significantly lowered blood glycosylated hemoglobin ( 0.8%), free fatty acid (43%), triglyceride (20%) and total cholesterol (28%) levels compare to control group. In high fat diet model, BLX-1002 reduced body weight gain and significantly (p<0.05) improved oral glucose tolerance. BLX-1002 does not induce adipogenesis, aP2 (fatty acid binding protein) or Acrp30 (adiponectin) expression in 3T3-L1 adipocytes or human pre-adipocytes and most probably it is not an agonist of PPARγ. BLX-1002 strongly inhibits lipopolysacharide (LPS) induced pro-inflammatory cytokines like IL-6 and TNFα production in both human monocytes and in animals. BLX-1002 rapidly induces 14C-Deoxyglucose uptake in isolated rat adipocytes, which was blocked by PI 3 kinase inhibitor LY294002. Similar to insulin, it also blocked isoproterenol induced lipolysis in both rat and human adipocytes. In Chinese hamster ovary cells, which over express the human insulin receptor (CHO.IR), BLX-1002 induces tyrosine phosphorylation of IRβ and insulin receptor substrate-1 (IRS-1) similar to insulin. In streptozotocin induced diabetes model in mice, it lowered blood glucose and triglyceride levels compare to controls. A repeat dose 28 days chronic toxicological studies in rats and dogs did not show any increase of liver enzymes (AST or ALT), BUN and creatinine levels. These results combined demonstrate the potential of BLX-1002 as a novel compound for the treatment of Type-II diabetes and related disorders. Am J Hypertens (2004) 17, 32A–32A; doi: 10.1016/j.amjhyper.2004.03.071</abstract><pub>Oxford University Press</pub><doi>10.1016/j.amjhyper.2004.03.071</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0895-7061 |
| ispartof | American journal of hypertension, 2004-05, Vol.17 (S1), p.32A-32A |
| issn | 0895-7061 1941-7225 |
| language | eng |
| recordid | cdi_istex_primary_ark_67375_HXZ_63CNX5HR_2 |
| source | Oxford University Press Journals All Titles (1996-Current) |
| subjects | Cytokines Diabetes Insulin Resistance |
| title | OR 72: Amino acid conjugated small molecule BLX-1002 lowers blood glucose in insulin resistant db/db and ob/ob mice and inhibits TNF-α , IL-6 cytokines |
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