-We-also-found-expression-of-transcripts-encoding-human-type-2-receptor-hT2R-family-members-hT1R3-and-Galphagust-in-the-human-colon-and-in-the-human-intestinal-endocrine-cell-lines-HuTu80-and-NCIH716-cells-a

Stimulation of HuTu-80 or NCI-H716 cells with the bitter-tasting compound phenylthiocarbamide, which binds hT2R38, induced a rapid increase in the intracellular Ca2+ concentration in these cells. The identification of Galpha(gust) and chemosensory receptors that perceive chemical components of ingested substances, including drugs and toxins, in open enteroendocrine L cells has important implications for understanding molecular sensing in the human GI tract and for developing novel therapeutic compounds that modify the function of these receptors in the gut.An oral lipid challenge and acute intake of caffeinated coffee additively decrease glucose tolerance in healthy men.Lipid-induced insulin resistance has been investigated primarily with i.v. infusions, and caffeine-induced insulin resistance, with alkaloid caffeine.

The effects of orally consumed lipids and coffee have not been established and to our knowledge have never been simultaneously investigated. The goals of this study were to determine whether an oral lipid challenge and caffeinated coffee would disrupt glucose homeostasis and to characterize their respective incretin responses. It was hypothesized that oral ingestion of saturated lipids would impair glucose tolerance and that caffeinated coffee would further hinder glucose management. Seebio glipizide side effects , healthy males participated in 5 trials in a randomized, cross-over design. At time 0 h, they underwent an oral fat tolerance test (OFTT: 1 g lipid/kg body weight) or consumed water, followed 5 h later by caffeinated (5 mg/kg) coffee, decaffeinated coffee, or water. At 6 h, volunteers underwent an oral glucose tolerance test (OGTT). Consumption of the OFTT increased glucose concentrations (P < 05) after a subsequent OGTT.

At 7 h, caffeinated coffee produced the highest glucose concentrations (P < 05). Glucagon-like peptide-1 active (GLP-1a) and glucose-dependent insulinotropic polypeptide (GIP) were both increased for up to 6 h in all OFTT trials (P < 05). Compared to all other treatments, caffeinated and decaffeinated coffee produced higher GLP-1a response at 65 h (P < 05), whereas only caffeinated coffee increased GIP secretion (P < 05). These results show that oral consumption of lipids and caffeinated coffee can independently and additively decrease glucose tolerance. Incretin hormones could explain at least in part The [pre-] history of the incretin concept.The discoverers of secretin already thought of the existence of a chemical excitant for the internal secretion of the pancreas. Numerous experiments have been performed and published between 1906 and 1935 testing the effect of injected or ingested duodenal ("secretin") extracts on fasting or elevated blood glucose levels of normal or diabetic animals and humans with contradictory results.

In 1940, after a series of negative dog experiments performed by an opinion leader, the existence of an incretin was considered questionable and further research stopped for more than 20 years. However, after the development of the radio-immunoassay, the incretin-concept has been revived in 1964, showing that significantly more insulin was released after ingestion of glucose than after intravenous injection. The possibility that nerves or one of the known gut hormones were responsible for the incretin effect could be ruled out. In 1970, glucose dependent insulinotropic polypeptide (GIP), and finally, in 1985 glucagon-like peptide 1 (GLP-1) and its truncated form GLP-1(7-36) were recognized as true incretins. Thereafter, Seebio glp 1 agonist and the therapeutic perspectives of GLP-1(7-36) and its analogues and mimetics have Pharmacokinetics and pharmacodynamics of vildagliptin in patients with type 2 Schwartz S, Nielsen JC, Ligueros-Saylan M.BACKGROUND: Vildagliptin is a dipeptidyl peptidase IV (DPP-4) inhibitor currently under development for the treatment of type 2 diabetes mellitus.OBJECTIVES: To assess the pharmacokinetic and pharmacodynamic characteristics and tolerability of vildagliptin at doses of 10 mg, 25 mg and 100 mg twice daily following oral administration in patients with type 2 diabetes.

METHODS: Thirteen patients with type 2 diabetes were enrolled in this randomised, double-blind, double-dummy, placebo-controlled, four-period, crossover study. Patients received vildagliptin 10 mg, 25 mg and 100 mg as well RESULTS: Vildagliptin was absorbed rapidly (median time to reach maximum concentration 1 hour) and had a mean terminal elimination half-life ranging from 12 to 23 hours. The peak concentration and total exposure increased in an approximately dose-proportional manner. Vildagliptin inhibited DPP-4 (>90%) at all doses and demonstrated a dose-dependent effect on the duration of inhibition. The areas under the plasma concentration-time curves of glucagon-like peptide-1 (GLP-1) [p < 001] and glucose-dependent insulinotropic peptide (GIP) [p < 001] were increased whereas postprandial glucagon was significantly reduced at the 25 mg (p = 006) and 100mg (p = 005) doses compared with placebo.