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No other potential conflicts of interest relevant to this article were reported.Mechanisms Controlling Glucose-Induced GLP-1 Secretion in Human Small Intestine.University, Adelaide, South Australia, Australia.Translating Nutritional Science to Good Health, University of Adelaide, Institute, Adelaide, South Australia, Australia.Intestinal glucose stimulates secretion of the incretin hormone glucagon-like peptide 1 (GLP-1). The mechanisms underlying this pathway have not been fully investigated in humans.

In this study, we showed that a 30-min intraduodenal glucose infusion activated half of all duodenal L cells in humans. This infusion was sufficient to increase plasma GLP-1 levels. With an ex vivo model using human gut tissue specimens, we showed a dose-responsive GLP-1 secretion in the ileum at ≥200 mmol/L glucose. In ex vivo tissue from the duodenum and ileum, but not the colon, 300 mmol/L glucose potently stimulated GLP-1 release. In the ileum, this response was independent of osmotic influences and required delivery of glucose via GLUT2 and mitochondrial metabolism. The requirement of voltage-gated Na+ and Ca2+ channel activation indicates that membrane depolarization occurs. Pancreatic hormones and other blood sugar regulating drugs do not drive this, as tolbutamide did not trigger release.

glp 1 drug -glucose cotransporter 1 (SGLT1) substrate α-MG induced secretion, and the response was blocked by the SGLT1 inhibitor phlorizin or by replacement of extracellular Na+ with N-methyl-d-glucamine. This is the first report of the mechanisms underlying glucose-induced GLP-1 secretion from human small intestine. Our findings demonstrate a dominant role of SGLT1 in controlling glucose-stimulated GLP-1 release in human ileal L cells.Anti-atherosclerotic effects of the glucagon-like peptide-1 (GLP-1) based therapies in patients with type 2 Diabetes Mellitus: A meta-analysis.China [2] Department of Endocrinology, Chinese PLA 309 Hospital, Beijing 100091, This study assessed the effect of GLP-1 based therapies on atherosclerotic markers in type 2 diabetes patients. 31 studies were selected to obtain data after multiple database searches and following inclusion and exclusion criteria. Age and BMI of the participants of longitudinal studies were 59 ± 8 years 20 weeks.

Percent flow-mediated diameter (%FMD) did not change from baseline significantly but when compared to controls, %FMD increased non-significantly following GLP-1-based therapies (15 [-09, 48]; P = 0; REM) in longitudinal studies and increased significantly in cross sectional studies (28 [18, 33]; P < 00001). Intima media thickness decreased statistically non-significantly by the GLP-1 based therapies. GLP-1 based therapies led to statistically significant reductions in the serum levels of brain natriuretic peptide (-406 [-510, -281]; P < 0001; REM), high sensitivity c-reactive protein (-07 [-08, -07]; P = 009), plasminogen activator inhibitor-1 (-120 [-258, 08]; P=05), total cholesterol (-57 [-95, -19]; P = 009), LDL-cholesterol (-30 [-79, -00]; P = 05) and triglycerides (-164 [-254, -73]; P = 0005) when mean differences with 95% CI in the changes from baselines were meta-analyzed. In conclusion, GLP-1-based therapies appear to provide beneficial effects against atherosclerosis. More randomized data will be required to arrive at conclusive evidence.Human glucagon-like peptides 1 and 2 activate rat brain adenylate cyclase.Two human glucagon-like peptides, GLP-1 and GLP-2, which are coencoded with pancreatic glucagon in the preproglucagon gene, do not significantly inhibit [125I]monoiodoglucagon binding to rat liver and brain membranes and do not activate adenylate cyclase in liver plasma membranes.

Nevertheless, GLP-1 and GLP-2 were each found to be potent stimulators of both rat hypothalamic and pituitary adenylate cyclase. Only 30-50 pM concentrations of each peptide elicited half-maximal adenylate cyclase stimulation. Our data suggest that GLP-1 and GLP-2 may be neurotransmitters and/or neuroendocrine effectors, which would account for their high degree of sequence conservation through vertebrate Mortality Reduction in EMPA-REG OUTCOME Trial: Beyond the Antidiabetes Effect.General Hospital, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada Two recent large-scale cardiovascular outcome trials, a now common tool in assessing the safety of pharmacological treatments for type 2 diabetes, reported significant reductions in all-cause mortality. In EMPA-REG OUTCOME [BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients], patients who received the SGLT2 inhibitor empagliflozin had a notable reduction of 9 deaths per 1,000 per year, while LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation) found that the patients receiving the GLP-1 receptor agonist liraglutide had a reduction of 3 deaths per 1,000 per year. The hypotheses to explain the sizable mortality reduction in EMPA-REG OUTCOME have mainly focused on the potential cardiovascular mechanisms of empagliflozin, but none considered its expected antidiabetes effects.