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Gastric mucosal defense and cytoprotection: bench to bedside.
Conditions in which mucosal injury is directly related to impairment in mucosal defense are discussed, focusing on disorders with important clinical sequelae: nonsteroidal anti-inflammatory drug (NSAID)-associated injury, which is primarily related to inhibition of cyclooxygenase-mediated PG synthesis, and stress-related mucosal disease (SRMD), which occurs with local ischemia.
Transient receptor potential vanilloid subfamily 1 expressed in pancreatic islet beta cells modulates insulin secretion in rats.
- Y. Akiba, S. Kato, +4 authors T. Hibi
- Biology, MedicineBiochemical and biophysical research…
- 13 August 2004
It is demonstrated for the first time that TRPV1 is functionally expressed in rat islet beta cells and plays a role in insulin secretion as a calcium channel and the influences of capsaicin on the food intake and energy consumption as well as on the pathophysiological regulation of pancreatic endocrine.
Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV.
- Jun Feng, Zhiyuan Zhang, +11 authors S. L. Gwaltney
- Chemistry, MedicineJournal of medicinal chemistry
- 19 April 2007
Alogliptin is a potent, selective inhibitor of the serine protease dipeptidyl peptidase IV (DPP-4) and related quinazolinone-based DPP-4 inhibitors provide sustained reduction of plasma D PP-4 activity and a lowering of blood glucose in animal models of diabetes.
Pathogenesis of NSAID-induced gastric damage: importance of cyclooxygenase inhibition and gastric hypermotility.
- K. Takeuchi
- MedicineWorld journal of gastroenterology
- 14 May 2012
Gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage, and the response, causally related with PG deficiency due to COX-1 inhibition, occurs prior to other pathogenic events such as increased mucosal permeability.
Overexpression of GPR40 in Pancreatic β-Cells Augments Glucose-Stimulated Insulin Secretion and Improves Glucose Tolerance in Normal and Diabetic Mice
The results suggest that G PR40 may have a role in regulating glucose-stimulated insulin secretion and plasma glucose levels in vivo and that pharmacological activation of GPR40 may provide a novel insulin secretagogue beneficial for the treatment of type 2 diabetes.
Discovery of TAK-875: A Potent, Selective, and Orally Bioavailable GPR40 Agonist.
- N. Negoro, Shinobu Sasaki, +17 authors Y. Momose
- MedicineACS medicinal chemistry letters
- 18 June 2010
Dihydrobenzofuran derivative 9a showed potent plasma glucose-lowering action and insulinotropic action during an oral glucose tolerance test in female Wistar fatty rats with impaired glucose tolerance, and is currently in clinical trials for the treatment of type 2 diabetes mellitus.
Inhibition of both COX-1 and COX-2 is required for development of gastric damage in response to nonsteroidal antiinflammatory drugs
- A. Tanaka, H. Araki, Y. Komoike, S. Hase, K. Takeuchi
- MedicineJournal of Physiology-Paris
- 31 December 2001
The results suggest that the gastric ulcerogenic property of conventional NSAIDs is not accounted for solely by COx-1 inhibition and requires the inhibition of both COX-1 andCOX-2.
TAK-875, an Orally Available G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1 Agonist, Enhances Glucose-Dependent Insulin Secretion and Improves Both Postprandial and Fasting Hyperglycemia in…
- Y. Tsujihata, R. Ito, +5 authors K. Takeuchi
- Chemistry, MedicineJournal of Pharmacology and Experimental…
- 1 October 2011
TAK-875 enhances glucose-dependent insulin secretion and improves both postprandial and fasting hyperglycemia with a low risk of hypoglycemia and no evidence of β cell toxicity.
Chronic administration of alogliptin, a novel, potent, and highly selective dipeptidyl peptidase-4 inhibitor, improves glycemic control and beta-cell function in obese diabetic ob/ob mice.
- Y. Moritoh, K. Takeuchi, T. Asakawa, O. Kataoka, H. Odaka
- Chemistry, MedicineEuropean journal of pharmacology
- 7 July 2008
Chronic treatment with alogliptin improved glycemic control, decreased triglycerides, and improved beta-cell function in ob/ob mice, and may exhibit similar effects in patients with type 2 diabetes.
Aggravation by Selective COX-1 and COX-2 Inhibitors of Dextran Sulfate Sodium (DSS)-Induced Colon Lesions in Rats
- Mitsuaki Okayama, S. Hayashi, Y. Aoi, H. Nishio, S. Kato, K. Takeuchi
- MedicineDigestive Diseases and Sciences
- 12 April 2007
The results suggest that endogenous prostaglandins (PGs) afford protection against colonic ulcersation, yet the COX isozyme responsible for the production of PGs differs depending on the stage of ulceration; COX-1 in the early stage andCOX-2 in the late stage.