The present invention is directed to the identification of a biomarker specifically located in the plasma membrane of pancreatic beta cells. It was selected by a Systems Biology approach on Massively Parallel Signal Sequencing datasets obtained in human islets and Affymetrix microarray datasets on human islets, purified rat primary beta and non beta cells and insulinoma cells. Based on a set of specific features the biomarker is a unique candidate for imaging and targeting strategies to study the pancreatic beta cell mass in health and disease (T1 D, T2D, pancreatic cancers, obesity, islet transplantation, beta cell regeneration). The five specific features of the selected biomarkers are: 1) Preferentially expressed in pancreatic islets as compared to surrounding tissues; 2) Higher expression in pancreatic beta cells than in pancreatic alpha cells or than in other islet non-beta cells; 3) Expression levels in pancreatic beta cells are higher or comparable to glucokinase which is an enzyme specifically expressed in the pancreatic beta cell; 4) Located in the membrane and as such targetable with antibodies, peptides or small molecules which allows imaging, targeting and immunohistochemistry; and 5) Expression is not induced during the process of inflammation of the beta cell mass and the protein is not enriched in T-cells and dendritic cells or in other cells participating in the inflammation process.

Eizirik; Decio L.

Flamez; Daisy

Salmon; Isabelle

Berton; Alix

Roland; Isabelle

Marechal; Daniel

Beckers; Marie-Claire

Hood; Leroy

Goodman; Nathan

Kutlu; Burak

Universite Libre de Bruxelles

Plasma membrane biomarkers preferentially expressed in pancreatic beta cells useful in imaging or targeting beta cells

The present invention relates to a screening method for determining whether a substance of interest is a substance which alters GPR40-mediated cell stimulating activities, comprising using a substance of interest, a biomembrane containing GPR40, or cells containing said biomembrane, and phospholipase or salts thereof. According to the present invention, substances involved in insulin secretion can be screened. In addition, according to the present invention, substance useful for the prevention or treatment of diabetes, diabetic complications and degenerative diseases, hyperglycemia, polyuria, ketonemia, acidosis, insulin resistance, impaired glucose tolerance, neurodegenerative diseases, insulinoma, cancers, hyperinsulinemia, hyperglyceridemia, fatty liver, hypoglycemia due to insulin hypersecretion, arteriosclerosis, hyperlipidemia, cerebral stroke, obesity, various diseases induced by diabetes or obesity, and the like.

Eisai R&amp;D Management Co., Ltd.

Method of screening substance useful in treating disease with the use of GPR40 and phospholipase

The invention relates to compounds of Formula I: ##STR00001## and its pharmaceutical acceptable salts, solvates, enantiomers, stereoisomers and hydrates thereof. Compounds of Formula I and and compositions comprising Formula I are used to treat patients with metabolic syndrome and may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, or parenteral administration, as a syrup, or for injection. More specifically, compounds and compositions of Formula I may be used to treatment of acute hypertension or-malignant hypertension, hypoglycemia in disease states such as insulinoma (a tumor producing insulin) or congenital hyperinsulinism, hyperuricemia, gout, dyslipidemia, obesity, urea cycle disorders, hyperglycemia, insulin resistance, diabetes mellitus, diabetes insipidus, type 1 diabetes, type 2 diabetes, microvascular complications, macrovascular complications, lipid disorders, prediabetes, obesity, arrhythmia, myocardial infarction, stroke, neuropathy, renal complications, hypertriglyceridemia and cardiovascular complications.

insulinoma/سمنة

Plasma membrane biomarkers preferentially expressed in pancreatic beta cells useful in imaging or targeting beta cells

Method of screening substance useful in treating disease with the use of GPR40 and phospholipase

Compositions and methods for the treatment of metabolic syndrome

قاعدة بيانات الأعشاب الطبية الأكثر اكتمالا التي يدعمها العلم