American Fancy Rat & Mouse Association

This article is from the WSSF 2008 AFRMA Rat & Mouse Tales news-magazine.


Diabetes in Rats

By Carmen Jane Booth, D.V.M., Ph.D.

Editor, Karen Robbins
Q We’ve had a couple people here recently have rats with diabetes. What can you tell us about this problem?

Answer by Carmen Jane Booth, D.V.M., Ph.D.

What is Diabetes Mellitus?

Diabetes mellitus is a chronic disorder of carbohydrate (sugar), fat, and protein metabolism that has the characteristic feature of too much glucose in the blood (hyperglycemia).

Review of Normal Insulin Physiology

In a normal rat (or any animal) glucose levels (homeostatis) are tightly regulated by three interconnected processes: the production of glucose from the liver, uptake and use of glucose by cells in the body, and insulin secretion by the beta cells in the pancreatic islets. The islets comprise 1–2% of the total pancreatic tissue in the adults. Islets of Langerhans (islets) from the endocrine pancreas which regulates blood glucose and the remainder of the pancreas is exocrine for production of digestive enzymes. (Figure 1 a & b).

The gene for insulin production is only expressed in pancreatic beta cells. Insulin is synthesized as a longer inactive protein called preproinsulin that through specific cleavage steps within beta cells ultimately becomes mature insulin. Mature insulin is stored in secretory granules within the beta cells to be available for secretion after physiologic stimulation.

When food is consumed, everything is digested so that fat, protein, and carbohydrates can be absorbed into the body in the intestine. Fats are broken down into fatty acids and triglycerides, proteins into more manageable peptides and amino acids, and carbohydrates (starches, glycogen) into more simple sugars, which are all ultimately broken down into simple sugars (glucose, galactose, and fructose). Glucose represents more than 80% of the final products of carbohydrate digestion. Once in the body, any excess glucose not required for energy is stored as glycogen (liver, muscle cell) and when these cells are saturated, the excess is converted to fat by the liver and stored in fat cells. Carbohydrates are used in preference to fat when excess carbohydrate is available. Excess fatty acids are stored converted to fat and stored in fat cells. Each particular type of cell has an upper limit to the amount of protein it can store. Excess protein is degraded, used for energy, or converted to fat or glycogen and stored for later use.

The most important stimulus that triggers insulin release is glucose uptake into beta cells. Transport of glucose into beta cells by the glucose transport protein (GLU-2) is not dependent on insulin. Once in the cell, glucose can stimulate both the immediate release of insulin from granules and if needed, more insulin synthesis. Although insulin has many functions, the following are necessary for energy metabolism.

  1. Transport of glucose and amino acids across cell membranes
  2. Formation of glycogen in the liver and skeletal muscles
  3. Glucose conversion into triglycerides
  4. Nucleic acid and protein synthesis
  5. Increase the rate of glucose transport into certain cells (cardiac, skeletal, muscle, and fat cells)

Diabetes Mellitus Classification

Diabetes mellitus (diabetes) represents a heterogeneous group of disorders that have hyperglycemia as a common feature. Any disease process that causes destruction of pancreatic islets can result in diabetes.

Primary Causes of Diabetes

Type 1 diabetes is insulin-dependent and often occurs in juveniles and accounts for 10% of all cases in humans. Former names: Juvenile onset, insulin-dependent diabetes mellitus.
Type 2 diabetes is not dependent on insulin and accounts for 80–90% of human cases. Former names: non-insulin dependent diabetes mellitus, adult onset diabetes.
Genetic defects of beta cell function account for less than 5% of diabetes in humans.

Secondary Causes of Diabetes

   Pancreatic infections
   Endocrine Tumors (adrenal gland, pituitary)
   Gestational diabetes mellitus

Figure Legend
Pancreas Histology
a) Normal exocrine pancreas.
b) Higher magnification of box in a) with islet of Langerhans (arrow).
c) NOD diabetic mouse pancreas.
d) Higher magnification of box in c) with massive inflammation surrounding the islet of Langerhans (arrow). (Modified from Hawiger 2007)

Type 1

In Type 1, body weight is normal, the age of onset is younger, and there is decreased blood insulin from anti-islet cell antibody mediated destruction of beta cells. This is seen early in the disease process as lymphocytes and plasma cell infiltration (insulitis) of the islets, and eventually as marked islet cell atrophy and beta cell depletion which leads ultimately to severe insulin deficiency (Figure 1 b & c). This type of diabetes is treated by insulin therapy. The underlying cause for the bodies attack on the beta cells is complex and not completely understood. In humans there is some genetic susceptibility in persons of Northern European descent.

Spontaneous Type 1 diabetes has been reported in both rats and mice. The two most common are the non-obese diabetic mouse (NOD) and the bio breeding (BB) rat and have similarities to human Type 1 diabetes. In both cases, the pancreatic islets are subjected to an immune attack and insulitis.

Clinical signs in BB rats include weight loss, excessive water consumption (polydipsia), excess urination (polyuria), elevated blood glucose (hyperglycemia), and low insulin levels (insulinopenia) around 12 weeks of age. The sustained high blood glucose results in severe ketoacidosis and death if untreated with insulin. Clinical signs in NOD mice are similar except that ketoacidosis is relatively mild. Prophylactic administration of insulin has had some success in preventing diabetes in these strains of rodents.

What is Ketoacidosis?

Ketoacidosis is a complication that occurs almost exclusively in Type 1 diabetes and is stimulated by severe insulin deficiency. In the absence of being able to utilize glucose for energy, the body switches to using ketones for energy. Ketone formation often exceeds ketone use and increased blood levels (ketonemia) and urine levels (ketouria) result. If ketone utilization and excretion in the urine cannot keep up with production, the blood levels increase to the point of ketoacidosis where the blood pH is lowered and breathing is affected and without treatment, ketoacidosis results in coma and death.

Type 2 Diabetes

In Type 2, body weight is obese, there is normal or increased blood insulin, the cells are resistant to insulin and there is no insulitis, some islet atrophy, amyloid deposition in islets, and mild beta cell depletion. Type 2 diabetes is characterized by insulin resistance and impaired insulin secretion and high blood glucose both with fasting and post feeding. In rodents with spontaneous Type 2 diabetes, some have increased insulin resistence and other beta cell failure predominate. The molecular basis of insulin resistance is unclear; however, regardless of the cause, the result is an inability of circulating insulin to direct glucose uptake by cells, persistent hyperglycemia, and prolonged stimulation of beta cells. Eighty percent of humans with Type 2 diabetes are obese with large stores of abdominal fat.

There are a number of rat and mouse strains with spontaneous Type 2 diabetes that have a genetic basis. Some are obese and some are not. I will only mention the three. The most well-known is the obese Zucker rat (fa/fa) which is obese, diabetic, and resistant to leptin (one of the hormones involved in signaling fat metabolism). Two mouse strains with obesity are the (Ob/Ob) mice that are leptin deficient, and the (db/db) mice which are leptin resistant. Clinical signs of polydipsia, polyuria, and glucose in the urine (glycosuria) are seen.


Long term complications of chronic hyperglycemia are similar regardless of which type of diabetes. The most frequent problems are related to accelerated thickening of blood vessels (atherosclerosis) throughout the body. In the heart, this can lead to heart attacks if the blood vessels to the heart become blocked and the heart muscle dies (myocardial infarction). In the kidney, damage to the glomeruli (involved in filtering the blood to make urine) can eventually result in kidney failure. The leading cause of death in humans with diabetes is myocardial infarction followed by renal failure. Chronic spilling of glucose into the urinary bladder can result in urinary track infections. Blindness from damage to the retina of the eyes, and nerve damage to peripheral nerves in the hands and feet are seen in diabetes. Wound healing is impaired in diabetics.

Blindness in rodents is not usually problematic as they are caged and can easily find their way to food and water by smell.

The peripheral neuropathy can present problems. Alison Campbell, (N.F.R.S., England) gives an excellent explanation in her article on “Diabetes in Rats.” Excerpt:

“Neuropathy – Diabetic rats have been shown to very quickly develop reduced nerve conduction velocity (the speed at which nervous impulses move in the body) and a loss of sensitivity (reduced nervous sensation). This can lead them to become clumsy and at the same time more susceptible to damage especially of the feet and tail. Wounds can quickly become infected and circulation tends to be poor so healing is slow. Other symptoms like itching, tingling, and numbness can cause the rat to shake its paws vigorously, drop food, and chew at its toes and fingers. The tail, hands, and feet of a diabetic rat should be inspected regularly for wounds, and treated swiftly should any damage occur.”

The clinical reports of spontaneous diabetes in pet rats and mice are sparse, so the actual incidence is unknown. Most cases are older rats that are obese. These rats present with symptoms similar to humans: polydipsia and polyuria. Advanced cases can present with weakness.


Diagnosis in rats can be made by testing blood or urine. Because diabetic rats and mice urinate frequently, you can place them in an empty cage and collect urine for your veterinarian. In a clinic, I usually can collect a few drops when I pick them up. There are urine test strips which make it easy to check for glucose, ketones, and protein in urine. Kidney problems are not uncommon in older rodents, so I always check urine for protein if possible. Blood glucose determination can also be performed if a clinic has a glucose meter that can run on a small drop of blood like people use at home who have diabetes. My preference is to clip a rear toe nail. If that is not an option, the tip of the tail can be nicked. I would suggest the tail tip or nail be numbed with lidocaine cream to decrease the discomfort to the rat or mouse.


Type 1 diabetes requires insulin. There are different forms of insulin. It has to be directed by a veterinarian and involves subcutaneous injections.

In both Type 1 and Type 2 diabetes, diet and exercise are extremely important. Exercise can help muscle cells burn fat to reduce obesity and also can help in glucose uptake in Type 2 diabetes. The principles for diet are similar for humans and animals. The diet needs to be low in simple sugars and high in fiber and complex carbohydrates. I would suggest using a base of dry dog food formulated for diabetic dogs that has high fiber with added beans, whole grains, etc. High fiber diets help lower blood glucose in diabetics. Low sugar treats can also be given (carrots, nuts, etc.).

There are oral medications used in Type 2 diabetes therapy (Glucophage and Galipizide); however, their use in pets rats with diabetes has not been reported.

“Animal models of diabetes mellitus.” Diabetic Medicine, UK 2005 (22) 359-370.

“Diabetes in Rats,” Pro-Rat-A 156, Nov.–Dec. 2006, by Alison Campbell, N.F.R.S., England.

“ICOS mediates the development of insulin-dependent diabetes mellitus in nonobese diabetic mice.” Hawiger, D., Tran, E., Du, W., Booth, C. J., Wen, L., Dong, C., Flavell, R.A. Journal of Immunology. 2008 Mar 1;180(5):3140-7.

Robbins Pathologic Basis of Disease, 6th Edition by R.S. Cotran, V. Kumar, and T. Collins. 1999 W. B. Saunders, Co.

Textbook of Medical Physiology 9th Edition by A. C. Guyton and J. E. Hall. 1996. W. B. Saunders, Co. *

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Updated April 10, 2014