Summary
Successful transplantation of isolated islets of Langerhans has been reported in large mammals, including man, but metabolic control has not been well-established. We studied the glucose and islet hormone response to fasting, i. v. glucose bolus infusion, i.v. arginine bolus infusion during a 35-mmol/l hyperglycaemic clamp, mixed meals, and i. v. insulin-induced hypoglycaemia up to 3 years after intrasplenic islet autotransplantation in six pancreatectomised dogs. The individual postprandial insulinogenic index (ratio of 2-h postprandial insulin to glucose levels) at 1 month post-transplant, predicted (r=0.99) the time to functional graft failure (6–175 weeks). Metabolic studies at 6 months post-transplant in four dogs demonstrated normal fasting glucose and hormone levels, except for reduced pancreatic polypeptide levels. Intravenous glucose and arginine-stimulated insulin were reduced to 15% of preoperative values. In contrast, postprandial normoin-sulinaemia was observed — albeit with moderate hyperglycaemia (approximately 10 mmol/l). Postprandial glucagon and glucose-dependent insulinotropic polypeptide (GIP) had increased. Comparison of the post-transplant insulin responses to a meal and to intravenous challenges demonstrated maximal stimulation of the graft by the meal. Post-transplant pancreatic polypeptide responses to a meal and i.v. arginine were severely reduced, and no pancreatic polypeptide response to i.v. insulin-induced hypoglycaemia was observed — indicating absence of cholinergic reinnervation. Thus, glucose regulation and both the insulin secretory capacity and life expectancy of islet grafts were best documented by meal testing. Tentatively, a postprandial hyperglycaemia-enhanced incretin effect of glucose-dependent insulinotropic polypeptide and other gut hormones may account for the difference in the insulin response to i. v. glucose and a meal. Aside from the reduced insulin secretory capacity, both a deranged pulsatile delivery of insulin, hyperglucagonaemia, and pancreatic polypeptide deficiency may have been conducive to glucose intolerance.
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Abbreviations
- IEq:
-
Islet equivalent
- IVGTT:
-
intravenous glucose tolerance test
- GIP:
-
glucose-dependent insulinotropic polypeptide
- PP:
-
pancreatic polypeptide
- RIA:
-
radioimmunoassay
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van der Burg, M.P.M., Guicherit, O.R., Jansen, J.B.M.J. et al. Function and survival of intrasplenic islet autografts in dogs. Diabetologia 39, 37–44 (1996). https://doi.org/10.1007/BF00400411
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DOI: https://doi.org/10.1007/BF00400411