Can myoglobin expression in pancreatic beta cells improve insulin secretion under hypoxia? An exploratory study with transgenic porcine islets.
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.
Tilakaratne
Himantha Kushanie
HK
Department of Chemical and Biochemical Engineering, The University of Iowa, IA, USA.
Yang
Baoli
B
Hunter
Stephen K
SK
Andracki
Mark E
ME
Rodgers
Victor G J
VG
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
D007328:Insulin; D009211:Myoglobin; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D005947:Glucose