The mechanisms of alloxan- and streptozotocin-induced diabetes.
Reads0
Chats0
TLDR
The targeting of mitochondrial DNA, thereby impairing the signalling function of beta cell mitochondrial metabolism, also explains how streptozotocin is able to inhibit glucose-induced insulin secretion, causing a state of insulin-dependent ‘alloxan diabetes’.Abstract:
Alloxan and streptozotocin are toxic glucose analogues that preferentially accumulate in pancreatic beta cells via the GLUT2 glucose transporter. In the presence of intracellular thiols, especially glutathione, alloxan generates reactive oxygen species (ROS) in a cyclic redox reaction with its reduction product, dialuric acid. Autoxidation of dialuric acid generates superoxide radicals, hydrogen peroxide and, in a final iron-catalysed reaction step, hydroxyl radicals. These hydroxyl radicals are ultimately responsible for the death of the beta cells, which have a particularly low antioxidative defence capacity, and the ensuing state of insulin-dependent 'alloxan diabetes'. As a thiol reagent, alloxan also selectively inhibits glucose-induced insulin secretion through its ability to inhibit the beta cell glucose sensor glucokinase. Following its uptake into the beta cells, streptozotocin is split into its glucose and methylnitrosourea moiety. Owing to its alkylating properties, the latter modifies biological macromolecules, fragments DNA and destroys the beta cells, causing a state of insulin-dependent diabetes. The targeting of mitochondrial DNA, thereby impairing the signalling function of beta cell mitochondrial metabolism, also explains how streptozotocin is able to inhibit glucose-induced insulin secretion.read more
Citations
More filters
Journal ArticleDOI
Epidemiology of type 1 diabetes.
TL;DR: The epidemiology of type 1 diabetes mellitus around the world and across the lifespan is described and data indicates that the incidence of T1D has been increasing by 2% to 5% worldwide and that the prevalence is approximately 1 in 300 in the United States by 18 years of age.
Journal ArticleDOI
Oxidative stress: the vulnerable β-cell
TL;DR: Antioxidative defence mechanisms of pancreatic beta-cells are particularly weak and can be overwhelmed by redox imbalance arising from overproduction of reactive oxygen and reactive nitrogen species.
Journal ArticleDOI
Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models.
Michael C. Deeds,Jarett M. Anderson,Adam Armstrong,Dennis A. Gastineau,Henry J. Hiddinga,A Jahangir,Norman L. Eberhardt,Yogish C. Kudva +7 more
TL;DR: The literature is reviewed and data from pancreatic islet transplantation experiments using single high-dose STZ-induced DM in NCr athymic nude mice are provided with hopes of providing clarification for study design, suggesting refinements to the process, and developing a more humane process of chemical diabetes induction.
Journal ArticleDOI
Modeling type 2 diabetes in rats using high fat diet and streptozotocin
TL;DR: The present review summarizes the current understanding of the metabolic profile and pathology involved in the different stages of the type 2 diabetes disease progression in humans and examines the suitability of the high‐fat diet‐fed, streptozotocin (HFD/STZ)‐treated rat model as a model of type 1 diabetes.
Journal ArticleDOI
High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats
Sunil K. Panchal,Hemant Poudyal,Abishek Iyer,Reeza Nazer,Ashraful Alam,Vishal Diwan,Kathleen Kauter,Conrad Sernia,Fiona Kumari Campbell,Leigh C. Ward,Glenda C. Gobe,Andrew Fenning,Lindsay Brown +12 more
TL;DR: In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.
References
More filters
Journal Article
The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas.
TL;DR: The cytotoxic action of both these diabetogenic agents is mediated by reactive oxygen species, however, the source of their generation is different in the case of alloxan and streptozotocin.
Journal ArticleDOI
Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells.
TL;DR: Insulin-producing cells cannot adapt the low antioxidant enzyme activity levels to typical situations of cellular stress by an upregulation of gene expression, and inactiva-tion of hydrogen peroxide through catalase seems to be a step of critical importance for the removal of reactive oxygen species in insulin- producing cells.
Journal ArticleDOI
Free radicals and diabetes
TL;DR: Not only are oxygen radicals involved in the cause of diabetes, they also appear to play a role in some of the complications seen in long-term treatment of diabetes.
Journal ArticleDOI
The generation of hydrogen peroxide, superoxide radical, and hydroxyl radical by 6-hydroxydopamine, dialuric acid, and related cytotoxic agents.
Gerald Cohen,Richard E. Heikkila +1 more
TL;DR: The results point to a reaction between H2O2 and O2- (Haber-Weiss reaction) as a major source of the ·OH radicals and to a combined action of blocking ·OH formation as well as accelerating its removal.