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We conclude that GLP-1(7-36) has the potential for being a modulator of ROOTS: A multicenter study in Belgium to evaluate the effectiveness and safety Collaborators: Abrams P, Bollaerts K, Buysschaert M, Corman V, Crepel T, Daubresse C, David JP, de Ryck P, Dehout F, Derdelinckx L, Dramais AS, Driessens N, Ers V, Gaham N, Heureux F, Houmont S, Hutsebaut A, Kleynen P, Leonet J, Marckx P, Mertens A, Nobels F, Nollet A, Plat F, Preumont V, Proces S, Remacle B, Robbrecht S, Scarniere D, Taelman P, Thissen JP, van der Donck P, van Ypersele M, Vandenbroucke M, Vanhaverbeke G, Vannimmen D, Verhaegen A, Yango Louvain, University Clinic St-Luc, Brussels, Belgium. Electronic address: Louvain, University Clinic St-Luc, Brussels, Belgium.AIMS: The ROOTS study was an observational study to evaluate the effectiveness patients with type 2 diabetes with inadequate glycaemic control despite conventional antihyperglycaemic dual therapy. The primary objective was to assess glycaemic control while using liraglutide under normal clinical practice conditions. The primary endpoint was to estimate the proportion of patients achieving improved glycaemic control defined as a HbA1c<7% or with a decrease of MATERIAL AND METHODS: The study included 245 subjects. They received liraglutide in addition to their usual dual therapy (metformin and sulfonylureas or pioglitazone). Age and duration (mean±SD) of diabetes were 58±10 and 9±5 years RESULTS: HbA1c decreased from 92%±18 at baseline to 74%±12 after one year follow-up (p<001). The primary endpoint was achieved in 66% of patients. In parallel, we observed a reduction of BMI from baseline 33±6 to liraglutide at a dosage of 1 mg/day, 32% received 1 mg and 2% 0 mg. Adverse drug reactions were present in 24% of subjects, most frequently gastrointestinal disorders (11%), mainly nausea (6%) and no pancreatic CONCLUSIONS: Treatment with liraglutide was associated with a marked improvement in glycaemic control in daily routine practice as well as with a reduction of SCO-267, a GPR40 Full Agonist, Improves Glycemic and Body Weight Control in Rat H.O., Y.Mi. , T.Y., Y.T., K.T., N. Endocrine function drugs .); and SCOHIA PHARMA, Inc., Kanagawa, Japan (S.A., M.O., A. K., M.W., Y.Y., T.M. , Y.Mo.).H.O., Y.Mi. , T.Y., Y.T., K.T., N. N.); and SCOHIA PHARMA, Inc., Kanagawa, Japan H.O., Y.Mi., T. Y., Y.T., K.T., N.N. ); and SCOHIA PHARMA, Inc., Kanagawa, Japan The GPR40/FFA1 receptor is a G-protein-coupled receptor expressed in the pancreatic islets and enteroendocrine cells. Here, we report the pharmacological (3S)-3-cyclopropyl-3-2-[(1-2-[(2,2-dimethylpropyl)(6-methylpyridin-2-yl)carbamoyl]-5-methoxyphenylpiperidin-4-yl)methoxy]pyridin-4-ylpropanoic acid (SCO-267), a novel full agonist of GPR40. Ca2+ signaling and insulin and glucagon-like peptide-1 (GLP-1) secretion were evaluated in GPR40-expressing CHO, MIN6, and GLUTag cells. Hormone secretions and effects on fasting glucose were tested in rats. Single or repeated dosing effects were evaluated in neonatally streptozotocin-induced diabetic rats (N-STZ-1 rats), diet-induced obese (DIO) rats, and GPR40-knockout (Ffar1-/– ) mice. glp-1 inhibitors with SCO-267 activated Gq signaling in both high- and low-FFAR1-expressing CHO cells, stimulated insulin secretion in MIN6 cells, and induced GLP-1 release in GLUTag cells. When administered to normal rats, SCO-267 increased insulin, glucagon, GLP-1, glucose-dependent insulinotropic peptide, and peptide YY (PYY) secretions under nonfasting conditions. These results show the full agonistic property of SCO-267 against GPR40. Hypoglycemia was not induced in SCO-267-treated rats during the fasting condition. In diabetic N-STZ-1 rats, SCO-267 was highly effective in improving glucose tolerance in single and 2-week dosing studies. DIO rats treated with SCO-267 for 2 weeks showed elevated plasma GLP-1 and PYY levels, reduced food intake, and decreased body weight. In wild-type mice, SCO-267 induced GLP-1 secretion, food intake inhibition, and body weight reduction; however, these effects were abolished in Ffar1-/– mice, indicating a GPR40-dependent mechanism. In conclusion, SCO-267 stimulated islet and gut hormone secretion, improved glycemic control in diabetic rats, and decreased body weight in obese rats. These data suggest the therapeutic potential of SCO-267 for the treatment of diabetes and obesity.Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying The insulinotropic hormone glucagon-like peptide-1 (GLP-1) is stored in the intestinal L cell in an active form, GLP-1-(7-36)amide, but more than half of the endogenous peptide circulates in an inactive, N-terminally truncated form, GLP-1-(9-36)amide. This study examined the GLP-1 newly secreted from the porcine ileum, in vitro (isolated perfused preparation) and in vivo (anesthetized pig), to determine where this conversion occurs. Although the GLP-1 extractable from the porcine ileum is predominantly the intact peptide (94+/-1%), a large proportion of the GLP-1 that is secreted has already been degraded to the truncated form both in vitro (53+/-0% intact) and in vivo (32+/-10% intact).