Pancreatic endocrine function in recipients of segmental and whole pancreas transplantation.
To determine potential abnormalities in beta-cell function after pancreas transplantation, the secretory capacity of the pancreatic grafts was assessed by measuring the glucose-potentiating effect on arginine-induced insulin secretion in recipients of cadaveric segmental (SPx; n = 8) and whole organ pancreas grafts (WPx; n = 6) and compared to that in nondiabetic kidney transplant recipients (Kx; n = 6) and normal controls (Ns; n = 7). alpha-Cell adaptation to increasing hyperglycemia and the glucagon response to arginine stimulation were also studied. The secretory capacity of the beta-cell to arginine-induced (5 g L-arginine) insulin secretion was measured at fasting plasma glucose and 15 and 30 mmol/L glucose. Insulin secretion was evaluated by the calculation of insulin secretion rates. Insulin sensitivity was markedly reduced in all three transplanted groups compared to that in normal subjects (P < 0.05). The prestimulation insulin secretion rate and maximal insulin secretion rate in response to hyperglycemia and arginine were significantly lower in SPx than in WPx, Kx, or Ns (P < 0.05). The incremental amount of insulin secreted in response to arginine was reduced by 40-70% in SPx depending on glycemia compared to that in all other groups (P < 0.05), among which there were no statistical differences. Both SPx and WPx demonstrated suppression of glucagon release in response to graded hyperglycemia, but failure to adequately suppress arginine-induced glucagon release. In conclusion, recipients of cadaveric segmental pancreas grafts display a markedly reduced maximal insulin secretory reserve capacity. This impairment was primarily due to an insufficient beta-cell mass. Taking the concomitant insulin resistance into account, recipients of a cadaver whole organ pancreas graft had an impaired insulin secretory reserve capacity as well.
Christiansen
E
E
Steno Diabetes Center, Gentofte, Denmark.
Tibell
A
A
Vølund
A
A
Rasmussen
K
K
Groth
C G
CG
Holst
J J
JJ
Pedersen
O
O
Christensen
N J
NJ
Madsbad
S
S
D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000379:methods / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D001120:Arginine; D005947:Glucose