CNTO736, a novel glucagon-like peptide-1 receptor agonist, ameliorates insulin resistance and inhibits very low-density lipoprotein production in high-fat-fed mice
| Jazyk: | angličtina |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
animal food
Blood Glucose Biomedical Research Fat intake Cytomegalovirus Inbred C57BL Mice glucagon like peptide 1 receptor Receptors Insulin lipoprotein metabolism C57BL mouse single drug dose very low density lipoprotein Liver hyperinsulinemia glucagon-like peptide receptor triacylglycerol Intravenous VLDL lipid diet Infusions Lipoproteins Recombinant Fusion Proteins animal experiment Drug potentiation Promoter Regions male Genetic blood Hyperinsulinism Genetics Animals controlled study glucagon like peptide receptor Biology mouse Triglycerides hybrid protein chronic drug administration nonhuman exendin 4 animal model Molecular cloning glucagon like peptide 1 derivative glucose transport Molecular glucagon receptor CNTO 736 Glucagon Animal Feed Dietary Fats Drug effect gluconeogenesis glucose blood level Metabolism Glucose Glucose Clamp Technique Intravenous drug administration Insulin Resistance Cloning |
| Popis: | CNTO736 is a glucagon-like peptide (GLP) 1 receptor agonist that incorporates a GLP-1 peptide analog linked to the Mimeti-body platform. We evaluate the potential of acute and chronic CNTO736 treatment on insulin sensitivity and very low-density lipoprotein (VLDL) metabolism. For acute studies, diet-induced insulin-resistant C57BL76 mice received a single intraperitoneal injection of CNTO736 or vehicle. Chronic effects were studied after 4 weeks of daily intraperitoneal administration. A hyperin-sulinemic- euglycemic clamp monitored insulin sensitivity. A single dose of CNTO736 reduced fasting plasma glucose levels (CNTO736, 4.4 ± 1.0; control, 6.3 ± 2.4 mM) and endogenous glucose production (EGP) (CNTO736, 39 ± 11; control, 53 ± 13 μmol/min/kg) and increased insulin-mediated glucose uptake (CNTO736, 76 ± 25; control, 54 ± 13 μmol/min/kg). Chronic administration of CNTO736 reduced fasting glucose levels (CNTO736, 4.1 ± 0.8; control 6.0 ± 1.0 mM), improved insulin-dependent glucose uptake (CNTO736, 84 ± 19; control, 61 ± 15 μmol/min/kg), and enhanced inhibition of EGP (CNTO736, 91 ± 18; control, 80 ± 10% inhibition). In addition, chronic dosing with CNTO736 reduced fasting EGP (CNTO736, 39 ± 9; control, 50 ± 8 μmol/min/kg) and VLDL production (CNTO736, 157 ± 23; control, 216 ± 36 μmol/h/kg). These results indicate that CNTO736 reinforces insulin's action on glucose disposal and production in diet-induced insulin-resistant mice. In addition, CNTO736 reduces basal hepatic glucose and VLDL output in these animals. The data suggest that CNTO736 may be a useful tool in the treatment of type 2 diabetes. Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics. |
| Databáze: | OpenAIRE |
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