title: Can myoglobin expression in pancreatic beta cells improve insulin secretion under hypoxia? An exploratory study with transgenic porcine islets.
abstract: The feasibility of myoglobin (Mb)-facilitated oxygen transport in improving porcine islet survival under hypoxia was investigated. Discrete groups of islets were transfected with replication-defective adenoviral vector Ad5 respiratory syncitial virus (RSV) to induce expression of Mb or green fluorescent protein (GFP). Native islets served as the controls. In vitro studies at 37 degrees C assessed islet insulin secretion efficacy: (i) to a glucose challenge from 30 to 300 mg/dL at fixed pO2; and (ii) at variable oxygen tensions ranging from 5 to 40 mm Hg over 12 h. The transfection was effective in initiating islet expression of Mb or GFP. Low Mb-expression levels equivalent to 2% the Mb concentration in a muscle cell (0.25 ng of Mb per islet) were documented, with no statistical improvement in insulin secretion. A surprising side note is that insulin secretion was impaired in islets expressing GFP. Improved Mb expression is essential to determine the feasibility of enhancing islet survival under hypoxia.
authors.affiliation: Department of Chemical and Biochemical Engineering, The University of Iowa, IA, USA.
authors.forename: Himantha Kushanie
authors.initials: HK
authors.lastname: Tilakaratne
authors.forename: Baoli
authors.initials: B
authors.lastname: Yang
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Hunter
authors.forename: Mark E
authors.initials: ME
authors.lastname: Andracki
authors.forename: Victor G J
authors.initials: VG
authors.lastname: Rodgers
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005818:Genetic Engineering; D005947:Glucose / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D009211:Myoglobin / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D013552:Swine; D013997:Time Factors
chemical_list: D007328:Insulin; D009211:Myoglobin; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D005947:Glucose