Induction of Type I Diabetes Mellitus in Beagle Dogs Using Alloxan and Streptozotocin

Abstract

This article describes a protocol for chemically inducing type I diabetes mellitus in beagle dogs using a mixture of alloxan (ALX) and streptozotocin (STZ). ALX and STZ are both cytotoxic, diabetogenic agents that cause necrosis of pancreatic β-cells and therefore halt the production of insulin. Although both compounds are widely used in experimental animal models of diabetes, standard protocols employing a single high dose of either agent are also implicated in adjacent organ damage. In contrast, combined administration of ALX and STZ allows for the use of lower doses, a method that effectively destroys β-cells and circumvents unwanted adverse effects. The procedures described in this protocol produce persistent, insulin-dependent hyperglycemia in beagle dogs using combined doses of ALX and STZ lower than those previously described for a single intravenous administration. This model can be used to test experimental compounds indicated for the treatment of diabetes.

Experimental type 1 diabetes metabolically rejuvenates CD8+T cells for improved control of tumor growth through an IGF1-IGF1R axis

“…The present study reports the novel finding that T1D predisposes the host to improved CD8 + T cell-mediated control of tumor growth in a generalized, pan-cancer manner (across a range of murine melanoma and carcinoma models). Streptozotocin (STZ) selectively destroys pancreatic beta cells and is widely used to develop models reflective of T1D (18,19). STZ enters cells through the glucose transporter 2 (Glut 2), which is expressed at high levels on pancreatic b cells, where it operationally functions as a glucose sensor (30).…”

“…Based on these unresolved findings, in the present study we examined the influence of streptozotocin-induced pre-existing T1D on cancer progression and associated immune alterations in a range of murine melanoma and carcinoma (i.e., breast, colon and lung) models. The streptozotocin induce T1D model was employed as this system is widely used in the field of endocrinology research (18,19). We found that the presence of T1D in the host yields an immunologically "hot" TME in which tumor growth is effectively controlled by antitumor CTL.…”