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Streptozotocin/High Fat Diet Model of Type 2 DiabetesSTZ High Fat Diet Model of Type 2 Diabetes

 

Recently, non-genetic rodent models have been developed which combine exposure to a high-fat diet with low doses of streptozotocin (STZ), a toxin that specifically targets the insulin–producing β-cells of the pancreas and destroys them through alkylation of DNA. These models are popular because they more closely mirror the metabolic disturbances observed in type 2 diabetic patients when compared to monogenetic rodent models of diabetes/obesity or dietary-induced obese rats and mice alone (which model insulin resistance but are not overtly diabetic).

 

We have validated STZ/high fat diet models of type 2 diabetes in both mice and rats. High fat fed animals treated with STZ display impaired glucose tolerance following a glucose challenge. Plasma insulin levels are markedly reduced in the animals given STZ compared to the vehicle-treated control group on the high fat diet.

Impaired Glucose Tolerance in STZ-treated Mice on High Fat Diet

 

STZ-treated mice on high fat diet exhibit significantly increased urinary glucose excretion and HbA1c compared to control animals.

Increased Urinary Glucose Excretion and Blood HbA1c in STZ-treated Mice on High Fat Diet

 

Our STZ/ high fat diet models of type 2 diabetes have been validated by showing that STZ treatment markedly reduces pancreatic insulin and insulin-secreting β-cells.

Reduced Pancreatic Insulin and Beta-cell Mass in STZ-treated Mice on High Fat Diet

 

The STZ/high fat model can therefore be used to screen for the beneficial effects of novel antidiabetic compounds on glycaemic control and to assess the ability of novel antidiabetic drugs to preserve β-cell function.

 

It can also be used to examine the effects of drugs on diabetic complications.

 

Please contact us for further information about our streptozotocin/high fat diet models of type 2 diabetes.

 

Posters

 

Poucher et al. 2010. Preservation of pancreatic beta cell-mass in high fat-fed STZ treated mice by the dipeptidyl peptidase-4 inhibitors saxagliptin and sitagliptin. Poster No. 567. European Association for the Study of Diabetes (EASD), Stockholm, Sweden, 20th-24th September 2010.

 

Vickers et al. 2011. Effect of STZ dose and dosing regimen on the diabetes phenotype of C57BL/6J mice fed a high fat diet. Diabetes Summit, Philadelphia, Pennsylvania, 7th-8th March 2011.

 

Vickers et al. 2012. Effect of empagliflozin on body weight, glucose control and plasma parameters in STZ-induced diabetic rats fed a high-fat diet: comparison with exenatide. Poster No. 771. European Association for the Study of Diabetes (EASD), Berlin, Germany, 1st-5th October 2012.

 

Manuscripts

 

Poucher et al. 2012. Effects of saxagliptin and sitagliptin on glycemic control and pancreatic β-cell mass in a streptozotocin-induced mouse model of type 2 diabetes. Diabetes Obes Metab 14(10): 918-926. [PubMed]