title: Assessing replication and beta cell function in adenovirally-transduced isolated rodent islets.
abstract: Glucose homeostasis is primarily controlled by the endocrine hormones insulin and glucagon, secreted from the pancreatic beta and alpha cells, respectively.  Functional beta cell mass is determined by the anatomical beta cell mass as well as the ability of the beta cells to respond to a nutrient load.  A loss of functional beta cell mass is central to both major forms of diabetes (1-3).  Whereas the declining functional beta cell mass results from an autoimmune attack in type 1 diabetes, in type 2 diabetes, this decrement develops from both an inability of beta cells to secrete insulin appropriately and the destruction of beta cells from a cadre of mechanisms.  Thus, efforts to restore functional beta cell mass are paramount to the better treatment of and potential cures for diabetes.    Efforts are underway to identify molecular pathways that can be exploited to stimulate the replication and enhance the function of beta cells.  Ideally, therapeutic targets would improve both beta cell growth and function.  Perhaps more important though is to identify whether a strategy that stimulates beta cell growth comes at the cost of impairing beta cell function (such as with some oncogenes) and vice versa.    By systematically suppressing or overexpressing the expression of target genes in isolated rat islets, one can identify potential therapeutic targets for increasing functional beta cell mass (4-6).  Adenoviral vectors can be employed to efficiently overexpress or knockdown proteins in isolated rat islets (4,7-15).  Here, we present a method to manipulate gene expression utilizing adenoviral transduction and assess islet replication and beta cell function in isolated rat islets (Figure 1).  This method has been used previously to identify novel targets that modulate beta cell replication or function (5,6,8,9,16,17).
authors: Department of Pediatrics, Indiana University School of Medicine, IN, USA. . pfueger@iupui.edu
authors: Patrick T
authors: PT
authors: Fueger
authors: Angelina M
authors: AM
authors: Hernandez
authors: Yi-Chun
authors: YC
authors: Chen
authors: E Scott
authors: ES
authors: Colvin
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D014161:Transduction, Genetic / Q000379:methods*