Diabetes & Diabetic Wound Healing


Clinical Background

Diabetes is a disease in which individuals lose the ability to regulate the level of sugar in their blood. This deregulation can lead to increased fat metabolism and a buildup of toxic metabolites (called ketone bodies) in the blood, which can cause diabetic coma and death. In the longer term, poorly controlled diabetes results in a variety of conditions that are caused by the excess sugar modifying key proteins. This results in conditions such as retinopathy (degeneration of the retina of the eye), nephropathy (kidney disease), neuropathy (nerve degeneration and pain) and ulceration of the skin.

Currently 15.7 million people, or 5.9 percent of the U.S. population, have diabetes. Approximately 2,200 people are diagnosed with diabetes each day. Diabetes is the seventh leading cause of death (sixth leading cause of death by disease) in the U.S. and contributed to 198,140 deaths in 1996. In any given year, approximately 5% of diabetics will suffer from an ulcer, usually on the foot, and approximately 1% will require amputation. Overall, 15% of patients with diabetes will develop foot ulcers in their lifetime and 12-24% of these patients will require the amputation of a foot.
Although there are currently many treatments for diabetes, none are a cure and many only work for a limited period of time, ultimately failing and leading to significant patient mortality.

Preclinical Models

Model Description Length Endpoints
Streptozotocin-induced diabetes
Chemical injury to pancreas to deplete insulin-producing cells 20-28 days Body weight, Blood glucose levels, Diabetic ulcer measurements, Clinical chemistry
Genetic diabetes
Zucker and ZDF rats, ob/ob and db/db mice 28-56 days Body weight, Blood glucose levels, Diabetic ulcer measurements, Clinical chemistry


Streptozotocin-induced diabetes

The streptozotocin-induced model of diabetes relies on a chemical injury to the pancreas to deplete the insulin-producing β-islet cells. This results in reduced insulin production and a disease that resembles type-1 diabetes. Because the induction is controlled, the onset of the disease is more reproducible than in the genetic models, making this process more efficient in terms of the number of animals used. Additionally, animals with any genetic background can be used in this model. Once disease has been induced and confirmed with a blood glucose test (and insulin measurements if required), the animals can then be used for the evaluation of drugs that treat diabetes and its complications.


A diabetic ulcer can be induced in a diabetic rat by surgically removing a piece of skin to create a wound. Once this wound is formed, the effectiveness of different treatments can be evaluated by measuring wound size or through histological evaluation of tissue taken after the animal has been euthanized. Animals are also weighed daily to track weight change and their blood glucose levels can be monitored. After animals are sacrificed, serum chemistry can be performed.

Genetic diabetes

There are numerous genetic models of diabetes in both rats and mice, including the Zucker and ZDF rats and ob/ob and db/db mice, in which diabetes develops spontaneously. A diabetic ulcer can be induced in a diabetic rat by surgically removing a piece of skin to create a wound. Once this wound is formed, the effectiveness of different treatments can be evaluated by measuring wound size or through histological evaluation of tissue taken after the animal has been euthanized. Animals are also weighed daily to track weight change and their blood glucose levels can be monitored. After animals are sacrificed, serum chemistry can be performed.