Abstract
Nonobese Diabetic (NOD) mice are susceptible strains for Type 1 diabetes development, and Nonobese Diabetes-Resistant (NOR) mice are defined as suitable controls for NOD mice in non-MHC-related research. Diabetes is often accelerated in NOD mice via Streptozotocin (STZ). STZ is taken inside cells via GLUT2 transmembrane carrier proteins, the major glucose transporter isoforms in pancreatic beta cells, liver, kidneys, and the small intestine. We observed severe adverse effects in NOR mice treated with STZ compared to NOD mice that were made diabetic with a similar dose. We suggested that the underlying mechanism could be differential GLUT2 expressions in pancreatic beta cells, yet immunofluorescent and immunohistochemical studies revealed similar GLUT2 expression levels. We also detected GLUT2 expression profiles in NOD and NOR hepatic and renal tissues by western blot analysis and observed considerably higher GLUT2 expression levels in liver and kidney tissues of NOR mice. Although beta cell GLUT2 expression levels are frequently evaluated as a marker predicting STZ sensitivity in animal models, we report here very different diabetic responses to STZ in two different animal strains, in spite of similar initial GLUT2 expressions in beta cells. Furthermore, use of NOR mice in STZ-mediated experimental diabetes settings should be considered accordingly.
Highlights
Nonobese Diabetic (NOD) mice are the most frequently preferred animal models in research related to type 1 diabetes (T1D) and other autoimmune conditions [1, 2]
While CY exerts its primary effect on CD4+CD25+ Treg cells [5], STZ is internalized through Glucose transporter 2 (GLUT2) glucose transporters which are located exclusively on beta cells in the pancreatic setting, and in liver, kidney, and small intestine cells
Streptozotocin (STZ) is a glucose analogue frequently used as a diabetic agent in various animal models
Summary
Nonobese Diabetic (NOD) mice are the most frequently preferred animal models in research related to type 1 diabetes (T1D) and other autoimmune conditions [1, 2]. Nonobese Diabetes-Resistant (NOR) mice are defined by the producer Jackson Lab as suitable control strains for NOD mice in non-MHC-related studies. STZ is an antibiotic produced by Streptomyces achromogenes and is used as an FDA-approved drug in the metastatic cancer of pancreatic islets cells It inhibits glucose oxidation and Journal of Diabetes Research glucose-induced insulin secretion in beta cells via nitric oxide production, alkylation, and DNA fragmentation [7,8,9,10]. While being a member of facilitative glucose transporters family which uptake and release glucose and other certain sugars, GLUT2 is unique in accepting fructose as a substrate and in its ability to act as a glucose sensor [11] It plays an important role in glucose homeostasis, functioning as a part of the glucose sensory mechanism in pancreatic beta cells [12]. GLUT2 expression levels in liver and kidney tissues of the two strains were compared by western blot protein analysis
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