title: Non-invasive bioluminescence imaging of β-cell function in obese-hyperglycemic [ob/ob] mice.
abstract: BACKGROUND
  Type 2 diabetes results from failure of the β-cells to compensate for increased insulin demand due to abnormal levels of metabolic factors. The ob/ob(lep-/-) mouse has been extensively studied as an animal model of type 2 diabetes. Previous studies have shown a correlation between β-cell function and bioluminescent imaging in lean genetically engineered mice. The ability to noninvasively monitor β-cell function in ob/ob mice could provide new information on β-cell regulation in type 2 diabetes.
  
  
  METHODS
  To create the B6 Albino ob/ob MIP-luc mice (ob/ob-luc), the ob/ob mouse was crossed with the CD1 MIP-luc mouse. All mice were backcrossed over multiple generations to ensure the genetic background of the transgenic mice was over 96% similar to the background of the original ob/ob mouse. Animal weight, blood glucose levels, insulin in plasma, and in vivo bioluminescence (BLI) were monitored weekly or biweekly for up to 70 weeks of age. BL imaging was performed using IVIS Spectrum (Perkin Elmer) and calculated by integrating the bioluminescence signal between 5 and 10 min after i.v. injection of D-luciferin. Insulin immunohistochemistry determined islet beta cell count and insulin secretion assay determined islet insulin function.
  
  
  RESULTS
  There were significant increases in BLI and insulin levels as the ob/ob-luc mice aged while glucose levels gradually decreased. Ob/ob-luc were sacrificed at different time points to determine ex vivo BLI, islet function and total β-cell numbers using a cell counting training algorithm developed for the Vectra image analysis system (Perkin Elmer). The number of β-cells increased as the mice aged and all three ex vivo measurements correlated with BLI.
  
  
  CONCLUSIONS
  The ob/ob-luc mice can serve as a model of metabolic stress, similar to human type 2 diabetes using BLI as a surrogate marker for β-cell function.
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Manishkumar
authors.initials: M
authors.lastname: Patel
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Alexa
authors.initials: A
authors.lastname: Gleason
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Stacey
authors.initials: S
authors.lastname: O'Malley
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Brett
authors.initials: B
authors.lastname: Connolly
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Donna
authors.initials: D
authors.lastname: Suresch
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Virostko
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Neil
authors.initials: N
authors.lastname: Phillips
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Shu-An
authors.initials: SA
authors.lastname: Lin
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Tsing-Bau
authors.initials: TB
authors.lastname: Chen
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Klimas
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hargreaves
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Sur
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, United States of America.
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Powers
authors.affiliation: Imaging Department, Merck Research Laboratories, Merck and Co., West Point, Pennsylvania, United States of America.
authors.forename: Bohumil
authors.initials: B
authors.lastname: Bednar
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D006943:Hyperglycemia / Q000503:physiopathology*; D007515:Islets of Langerhans / Q000503:physiopathology*; D049449:Luminescence; D051379:Mice; D009765:Obesity / Q000503:physiopathology*