title: Streptozotocin is equally diabetogenic whether administered to fed or fasted mice.
abstract: Streptozotocin (STZ) is a selective pancreatic β cell toxin used to generate experimental hyperglycemia in rodent models. Several laboratory animal protocols suggest that STZ be administered to fasted rodents to minimize competition between STZ and glucose for low affinity GLUT2 transporters on β cells. However, whether the diabetogenic effects of multiple low dose (MLD)-STZ administration are enhanced by fasting has not been addressed. Given that repeated bouts of fasting can cause undue metabolic stress in mice, we compared the efficacy of MLD-STZ injections (50 mg/kg body weight daily for 5 days) to induce experimental hyperglycemia in both NOD/SCID/γchain(null) and C57BL/6J mice that were either ad libitum fed (STZ-Fed) or that had been fasted for 6 h (STZ-Fasted) prior to the time of STZ administration. Both STZ-Fed and STZ-Fasted mice had significantly worse glucose tolerance than vehicle-treated control mice 10 days after initiation of the MLD-STZ regimen. In C57BL/6J mice, fasting glucose levels, serum insulin levels, β cell mass, and glucose disposal during intraperitoneal glucose tolerance tests (IPGTTs) were indistinguishable between STZ-Fed and STZ-Fasted mice 20 days after MLD-STZ. The glucose intolerant phenotypes persisted for 20 weeks thereafter, irrespective of whether C57BL/6J mice were fed or fasted at the time of STZ injections. However, STZ-Fasted C57BL/6J mice experienced significant weight loss during the repeated bouts of fasting/re-feeding that were required to complete the MLD-STZ protocol. In summary, induction of experimental hyperglycemia can be achieved using the MLD-STZ protocol without repeated bouts of fasting, which have the potential to cause metabolic stress in laboratory mice.
authors.affiliation: Departments of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Zunaira Z
authors.initials: ZZ
authors.lastname: Chaudhry
authors.forename: David L
authors.initials: DL
authors.lastname: Morris
authors.forename: Dan R
authors.initials: DR
authors.lastname: Moss
authors.forename: Emily K
authors.initials: EK
authors.lastname: Sims
authors.forename: Yien
authors.initials: Y
authors.lastname: Chiong
authors.forename: Tatsuyoshi
authors.initials: T
authors.lastname: Kono
authors.forename: Carmella
authors.initials: C
authors.lastname: Evans-Molina
mesh_terms: D000824:Animal Nutritional Physiological Phenomena / Q000187:drug effects*; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced*; D004195:Disease Models, Animal; D005508:Food Deprivation; D005951:Glucose Tolerance Test / Q000662:veterinary; D006943:Hyperglycemia / Q000139:chemically induced; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology*; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin
keywords: animal protocol refinement; diabetes; fasting; streptozotocin