Antidiabetic actions of an estrogen receptor β selective agonist.
The estrogen receptor β (ERβ) is emerging as an important player in the physiology of the endocrine pancreas. We evaluated the role and antidiabetic actions of the ERβ selective agonist WAY200070 as an insulinotropic molecule. We demonstrate that WAY200070 enhances glucose-stimulated insulin secretion both in mouse and human islets. In vivo experiments showed that a single administration of WAY200070 leads to an increase in plasma insulin levels with a concomitant improved response to a glucose load. Two-week treatment administration increased glucose-induced insulin release and pancreatic β-cell mass and improved glucose and insulin sensitivity. In addition, streptozotocin-nicotinamide-induced diabetic mice treated with WAY200070 exhibited a significant improvement in plasma insulin levels and glucose tolerance as well as a regeneration of pancreatic β-cell mass. Studies performed in db/db mice demonstrated that this compound restored first-phase insulin secretion and enhanced pancreatic β-cell mass. We conclude that ERβ agonists should be considered as new targets for the treatment of diabetes.
Institute of Bioengineering and Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, Miguel Hernandez University of Elche, Alicante, Spain. Alonso-Magdalena, palonso@umh.es
Paloma
P
Alonso-Magdalena
Ana B
AB
Ropero
Marta
M
García-Arévalo
Sergi
S
Soriano
Iván
I
Quesada
Sarheed J
SJ
Muhammed
Albert
A
Salehi
Jan-Ake
JA
Gustafsson
Angel
A
Nadal
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay; D047629:Estrogen Receptor beta / Q000819:agonists*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009536:Niacinamide / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D013311:Streptozocin / Q000494:pharmacology
D047629:Estrogen Receptor beta; D007004:Hypoglycemic Agents; D007328:Insulin; D010080:Oxazoles; D010636:Phenols; C502077:WAY 200070; D009536:Niacinamide; D013311:Streptozocin