Basal and nutrient-stimulated pancreatic and gastrointestinal hormone concentrations in type-l-diabetic patients after successful combined pancreas and kidney transplantation

The secretion of pancreatic and gastrointestinal hormones in the basal state and after nutrient stimuli (50 g glucose, 50 g protein, or 30 g triglyceride administered on separate occasions) was assessed in ten previously type-1-diabetic patients after successful combined kidney and pancreas transplantation (systemic venous drainage). Fasting values were compared to matched non-diabetic kidney-transplanted patients and related to kidney function (endogenous creatinine clearance) and to the type and dosage of immunosuppressive medication. In the fasting state, only IR insulin concentrations were higher in pancreas-kidney-transplanted patients (by 88%; P=0.001) than in the kidney graft recipients. There were significant inverse correlations of plasma C-peptide, GIP, and gastrin immunoreactivity to endogenous creatinine clearance (kidney function). In response to nutrients, insulin secretion (IR insulin, C-peptide) was significantly stimulated by glucose, and — to a lesser degree — also by protein. Pancreatic glucagon was suppressed by glucose and stimulated by protein ingestion. GIP was raised after glucose and triglyceride more than after protein (P=0.0003). GLP-1 immunoreactivity was stimulated by all nutrients, with a tendency towards higher responses to protein and fat (P=0.06). Gastrin was mainly raised by protein. In conclusion, the overall pattern of pancreatic and gastrointestinal hormone release is normal in patients after combined pancreas-kidney-transplantation, but there are some peculiarities due to (a) systemic venous drainage of the pancreas graft (elevated fasting IR insulin) and (b) impaired kidney function (negative correlation of fasting plasma values to endogenous creatinine clearance for C-peptide, GIP, and gastrin). The plasma levels of these important regulatory peptides and their responses to nutrient stimulation are compatible with and may contribute to the well-preserved endocrine function of the pancreatic grafts (normal or slightly impaired glucose tolerance, preserved incretin effect).