Treatment of Severely Diabetic Pancreatectomized Dogs Using a Diffusion-Based Hybrid Pancreas

Abstract

Long-term survival of dog islet allografts implanted in diabetic pancreatectomized dogs was achieved by islet encapsulation inside cylindrical chambers fabricated from permselective acrylic membranes (nominal Mr exclusion of 50,000–80,000). Dog islets were isolated from the pancreases of outbred mongrel dogs by collagenase digestion. Chambers containing mean ± SE 316 ± 63K islet equivalents (mean islet volume, 558 ± 111 mm3, purity 90–95%) were peritoneally implanted into six totally pancreatectomized dogs. The dogs were monitored for glycemic control by fasting and postprandial blood glucose determinations, and responses to both intravenous glucose (intravenous glucose tolerance test 0.5 g/kg) and oral glucose (oral glucose tolerance test 1 g/kg). All of the dogs required appreciably lower dosages of exogenous insulin therapy for control of fasting blood glucose levels, with the mean daily insulin dose dropping from 38 ± 7 to 5 ± 1 U/day during the 1st wk. Three recipients required no insulin for >82, >68, and 51 days. Intravenous glucose tolerance test K values (decline in glucose levels, %%min) at 1 and 2 mo postimplantation were 2.7 ± 0.4 and 2.0 ± 0.5, respectively compared with 3.5 ± 0.5 before pancreatectomy. The glucose values during oral glucose tolerance tests at 2 wk, although returning to < 125 mg/dl (< 7.0 mM) by 2 h, exceeded the normal range, with peak values of 174 to 202 mg/dl (9.7 to 11.3 mM). These preliminary results are encouraging, and represent an important step in determining the feasibility of using this type of diffusion-based hybrid artificial pancreas as treatment for diabetes mellitus in humans.