I. Establish diabetic state of recipient dog. Diabetes caused by surgical pancreatectomy (or dog is spontaneously diabetic). Following proof of the diabetic state, the animal will be treated with insulin injections to maintain euglycemia.

  • A. Plasma glucose levels.
  • B. Intravenous glucose tolerance test (IVGTT).
  • C. Metabolic studies.

II. Restore euglycemia with bio-artificial pancreas.

  • A. Islet sheets (5000 to 8000 islets/kg) will be transplanted into diabetic dogs.
  • B. The animal will be weaned from insulin injections at the approximate rate of 1 U/day. If the plasma glucose concentration is greater than 250 mg/dL after cessation of injected insulin, the device will be considered to have failed. Euthanasia, autopsy and histopathology will be performed at this time.
  • C. If rejection does not occur, functioning grafts will be studied histologically at three months, six months and one year.

III. Return of metabolic parameters to normal range.

  • A. Nonfasting plasma glucose levels will be determined daily, starting the day after transplantation.
  • B. Metabolic studies.

IV. Reestablish diabetic state.

  • A. Remove the sheet(s) containing the transplanted islets.
  • B. Metabolic studies. Return of metabolic parameters to the diabetic levels.
  • C. Histopathology. Quantify viable islets in removed sheet using perifusion and immunocytochemical techniques (i.e. insulin, glucagon, and somatostatin).