title: Glucose Effectiveness: The Mouse Trap in the Development of Novel ß-Cell Replacement Therapies.
abstract: BACKGROUND
  Cure of diabetes and normalization of glucose disposal during intravenous glucose tolerance tests (IVGTT) remains critical for stringent evaluation of novel replacement therapies in type 1 diabetes. Glucose disposal during an IVGTT depends on a complex interaction of both insulin-dependent and -independent mechanisms. Glucose effectiveness, that is, the function of glucose per se, independent of insulin, to stimulate its uptake and suppress endogenous glucose production is less recognized.
  
  
  METHODS
  To unravel the relative importance of these pathways, rats were injected with streptozotocin to induce diabetes and implanted subcutaneously with slow-release devices of insulin.
  
  
  RESULTS
  These animals demonstrated rapid normalization of blood glucose and perfectly normal glucose disposal during an IVGTT with no differences when compared with nondiabetic controls even though no active c-peptide secretion was detected in plasma and almost no remaining insulin-producing cells were present in the pancreas.
  
  
  CONCLUSIONS
  The present study highlights that glucose is the predominant mediator of its own disposal in rodents having only basal and nonglucose-regulated plasma insulin levels. The herein presented results calls for a reassessment how results obtained in the most commonly used experimental models should be interpreted in the development of future replacement therapies in type 1 diabetes.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Korsgren
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004343:Drug Implants; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004343:Drug Implants; D007004:Hypoglycemic Agents; D007328:Insulin