A Simplified Streptozotocin-Induced Diabetes Model in Nude Mice

Abstract

Preclinical studies of human cellular and tissue-based products (HCT/Ps) for transplantation therapy of type 1 diabetes mellitus (T1DM) necessarily involve animal models, particularly mouse models of diabetes induced by streptozotocin (STZ). These models should mimic the clinical and metabolic manifestations of T1DM in humans (face validity) and be similar to T1DM in terms of the pathogenetic mechanism (construct validity). Furthermore, since HCT/Ps contain human cells, modeling of diabetes in immune-deficient animals is obligatory. Here we describe the most simplified diabetes model in Nude mice. Diabetes was induced in 31 males by a single intraperitoneal injection of STZ in normal saline at a medium-to-high dose of 150 mg/kg body weight. Fourteen control animals received only saline. Non-fasting plasma glucose (PG) levels were measured periodically for 50 days. All STZ-treated mice survived beyond 50 days. By day 15 after STZ administration, 22 of 31 (71%) mice developed stable diabetes based on the following criteria: (1) non-fasting PG 15 mmol/L on consecutive measurements up until day 50; (2) no diabetes remission. The mean non-fasting PG in mice with stable diabetes over the period of 35 days was equal to 25.7 mmol/L. On day 50, mean plasma insulin concentration, mean pancreatic insulin content, and the average number of -cells in pancreatic islets were 2.6, 8.4, and 50 times lower, respectively, than in the control animals. We consider that our Nude mouse model of diabetes meets face validity and construct validity criteria and can be used in preclinical studies of HCT/Ps.

Deficient DNASE1L3 facilitates neutrophil extracellular traps‐induced invasion via cyclic GMP‐AMP synthase and the non‐canonical NF‐κB pathway in diabetic hepatocellular carcinoma

“…Diabetic animal models were established as described previously. 17 , 38 Firstly, the nude mice were randomly divided into two groups: diabetes mellitus (DM, n = 30) and control ( n = 10). In the DM group, the mice were fed a high‐fat and carbohydrate diet for a week, followed by a combination of a single intraperitoneal injection of streptozotocin (1% w/v solution in fresh cold sodium citrate buffer, pH 4.4) at a dose of 150 mg kg −1 .…”

“…Diabetic animal models were established as described previously 17,38 . Firstly, the nude mice were randomly divided into two groups: diabetes mellitus (DM, n = 30) and control ( n = 10).…”

Streptozotocin as a tool for induction of rat models of diabetes: a practical guide

“…STZ is mostly injected through IV and IP routes; however, intracardiac, subcutaneous, and intramuscular administration of STZ have also been reported (Deeds et al, 2011[ 19 ]; Ghasemi et al, 2014[ 36 ]). Intraperitoneal injection of STZ is easier, much more used, and has a high reproducibility (Chaudhry et al, 2013[ 14 ]; Gvazava et al, 2020[ 44 ]). However, it has been found to be associated with risk of intestinal injury and mortality, and its penetration into the subcutaneous tissue reduces its diabetogenic effect (Deeds et al, 2011[ 19 ]; Gvazava et al, 2020[ 44 ]).…”

“…Intraperitoneal injection of STZ is easier, much more used, and has a high reproducibility (Chaudhry et al, 2013[ 14 ]; Gvazava et al, 2020[ 44 ]). However, it has been found to be associated with risk of intestinal injury and mortality, and its penetration into the subcutaneous tissue reduces its diabetogenic effect (Deeds et al, 2011[ 19 ]; Gvazava et al, 2020[ 44 ]). Thus STZ dosage required to achieve the same level of diabetes via the IP route is higher than the IV route (Tesch and Allen, 2007[ 133 ]).…”