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CNTO736, a novel glucagon-like peptide-1 receptor agonist, ameliorates insulin resistance and inhibits very low-density lipoprotein production in high-fat-fed mice


, : CNTO736, a novel glucagon-like peptide-1 receptor agonist, ameliorates insulin resistance and inhibits very low-density lipoprotein production in high-fat-fed mice. Journal of Pharmacology and Experimental Therapeutics 328(1): 240-248

CNTO736 is a glucagon-like peptide (GLP) 1 receptor agonist that incorporates a GLP-1 peptide analog linked to the Mimetibody 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 C57BL/6 mice received a single intraperitoneal injection of CNTO736 or vehicle. Chronic effects were studied after 4 weeks of daily intraperitoneal administration. A hyperinsulinemic-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 micromol/min/kg) and increased insulin-mediated glucose uptake (CNTO736, 76 +/- 25; control, 54 +/- 13 micromol/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 micromol/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 micromol/min/kg) and VLDL production (CNTO736, 157 +/- 23; control, 216 +/- 36 micromol/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.

US$19.90

PMID: 18849357

DOI: 10.1124/jpet.108.144154


Other references

Berney, F.L., 1907: Field-notes on birds of the Richmond district, North Queensland. Part v. Emu Melbourne, 6 155-159

L.B.udec, J.; Marques-Vidal, P.; Cornuz, J.; Clair, C., 2016: Smoking cessation and the incidence of pre-diabetes and type 2 diabetes: a cohort study. Smoking cessation has been suggested to increase the short-term risk of type 2 diabetes mellitus (T2DM). This study aimed at assessing the association between smoking cessation and incidence of T2DM and impaired fasting glucose (IFG). Data from pa...

Sawhney, N.; Srivastava, N.K., 1979: An approach to accelerate acceptance of family planning services in rural areas. Report of an experiment combining education and motivation for family planning with distribution of medicines for minor ailments by a local "contact person" selected from each of 5 rural villages in Lucknow during 6 months in 1976-77. Th...

Shapiro, J.S., 1968: Ulnar drift. Report of a related finding. Acta Orthopaedica Scandinavica 39(3): 346-353

Kalir, A.; Poljakoff-Mayber, A., 1975: Malic dehydrogenase from tamarix tetragyna roots effects of sodium chloride in vivo and in vitro. Plant Physiology (Rockville) 55(2): 155-162

Rodríguez-Liñán, G.M.; Nahmad-Molinari, Y., 2006: Granular convection driven by shearing inertial forces. Convection velocity measurements in vertically vibrated granular materials are presented. The convection velocity close to the walls grows quadratically with the difference between the maximum and critical, or excess, amplitude (proposed as a dyna...

Kochummen, K.M., 1980: Botanical name changes of some common Malayan timber trees. Correct botanical names are listed for 36 species, with their commonly used synonyms and Malay common names.

Shapiro, D.; Leiderman, P.H., 1967: Arousal correlates of task role and group setting. Journal of Personality and Social Psychology 5(1): 103-107

Russell, R.C., 2017: Brian H. Kay: 1944-2017. Journal of the American Mosquito Control Association 33(3): 253-254

Tong, D.; Poot, M.; Hu, D.; Oda, D., 2000: 5-Fluorouracil-induced apoptosis in cultured oral cancer cells. Chemotherapy is commonly used to treat advanced oral squamous cell carcinoma (SCC) and is known to kill cancer cells through apoptosis. Our hypothesis states that 5-fluorouracil (5FU) also kills cultured oral epithelial cells through programmed ce...