title: A low-oxygenated subpopulation of pancreatic islets constitutes a functional reserve of endocrine cells.
abstract: OBJECTIVE
  The blood perfusion of pancreatic islets is highly variable and tightly regulated by the blood glucose concentration. Thus, oxygen levels are considered crucial for islet metabolism and function. Although islet oxygenation has been extensively studied in vitro, little is known about it in vivo. The current study aimed to investigate the oxygenation of the endocrine pancreas in vivo.
  
  
  METHODS
  The reductive metabolism of 2-nitroimidazoles, such as pimonidazole, has previously been extensively used in studies of oxygen metabolism both in vitro and in vivo. At tissue oxygen levels <10 mmHg, pimonidazole accumulates intracellularly and may thereafter be detected by means of immunohistochemistry. Islet oxygenation was investigated in normal, 60% partially pancreatectomized, as well as whole-pancreas-transplanted rats. Moreover, leucine-dependent protein biosynthesis was performed using autoradiography to correlate islet oxygenation with metabolic activity.
  
  
  RESULTS
  In vivo, 20-25% of all islets in normal rats showed low oxygenation (pO(2) <10 mmHg). Changes in the islet mass, by means of whole-pancreas transplantation, doubled the fraction of low-oxygenated islets in the endogenous pancreas of transplanted animals, whereas this fraction almost completely disappeared after a 60% partial pancreatectomy. Moreover, oxygenation was related to metabolism, since well-oxygenated islets in vivo had 50% higher leucine-dependent protein biosynthesis, which includes (pro)insulin biosynthesis.
  
  
  CONCLUSIONS
  The current study suggests a novel subpopulation of dormant low-oxygenated islets, which seems to constitute a functional reserve of endocrine cells. This study establishes a novel perspective on the use of the endocrine pancreas in glucose homeostasis.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. richard.olsson@karolinska.se
authors.forename: Richard
authors.initials: R
authors.lastname: Olsson
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Carlsson
mesh_terms: D000818:Animals; D019069:Cell Respiration; D007515:Islets of Langerhans / Q000098:blood supply / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D009593:Nitroimidazoles; D010100:Oxygen / Q000378:metabolism*; D010179:Pancreas / Q000502:physiology; D010180:Pancreatectomy; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D011920:Rats, Inbred WF; D046509:Tissue Culture Techniques
chemical_list: D009593:Nitroimidazoles; C033815:pimonidazole; D010100:Oxygen