-Deficient Mice with an Atherosclerosis-Resistant Background Develop Severe Hyperglycemia and Type 2 Diabetes on a Western-Type Diet.

and mice are two animal models extensively used for atherosclerosis research. We previously reported that mice on certain genetic backgrounds, including C3H/HeJ (C3H), develop type 2 diabetes when fed a Western diet. We sought to characterize diabetes-related traits in C3H- mice through comparing with C3H- mice. On a chow diet, mice had lower plasma total and non-HDL cholesterol levels but higher HDL levels than mice. Fasting plasma glucose was much lower in than mice (male: 122.5 ± 5.9 vs. 229.4 ± 17.5 mg/dL; female: 144.1 ± 12.4 vs. 232.7 ± 6.4 mg/dL). When fed a Western diet, and mice developed severe hypercholesterolemia and also hyperglycemia with fasting plasma glucose levels exceeding 250 mg/dL. Both knockouts had similar non-HDL cholesterol and triglyceride levels, and their fasting glucose levels were also similar. Male mice exhibited greater glucose tolerance and insulin sensitivity compared to their counterpart. Female mice showed similar glucose tolerance and insulin sensitivity though mice had higher non-fasting glucose levels. Male and mice developed moderate obesity on the Western diet, but female mice did not. These results indicate that the Western diet and ensuing hyperlipidemia lead to the development of type 2 diabetes, irrespective of underlying genetic causes.