Physiological and pharmacological stimulation of pancreatic islet hormone secretion in type I diabetic pancreas allograft recipients.
Successful heterotopic and denervated pancreas allograft transplantation (PAT) often results in normoglycemia and peripheral hyperinsulinemia in insulin-dependent (type I) diabetic recipients. The contribution of altered hepatic insulin extraction (HIE) to the resulting hyperinsulinemia in such patients remains uncertain. Furthermore, whether the denervated pancreas allografts exhibit beta-cell hyperresponsiveness to physiological and pharmacological stimulation is controversial. We evaluated beta-cell function and HIE after successful whole cadaveric PAT with systemic venous drainage in 13 type I diabetic patients before and after mixed-meal and intravenous glucose and glucagon administration. The results were compared with those of 5 nondiabetic patients with kidney transplantation only, who had native innervated pancreases with portal insulin delivery and were receiving an equivalent triple immunosuppressive therapy (cyclosporin, azathioprine, and prednisone), and 7 healthy control subjects with no family history of diabetes. After PAT, fasting and poststimulation serum glucose concentrations were normalized. PAT was associated with marked basal hyperinsulinemia (3- to 8-fold) as assessed by immunoreactive insulin (IRI) levels in type I diabetic patients (mean +/- SE 345 +/- 43 pM) compared with control subjects (43 +/- 14 pM) and nondiabetic kidney-transplantation patients (129 +/- 38 pM). After mixed-meal ingestion, the mean incremental integrated insulin area was similar in PAT patients (18 +/- 3 nM.min) compared with kidney-transplantation patients (20 +/- 4 nM.min) and healthy control subjects (21 +/- 3 nM.min). Basal serum C-peptide levels were significantly greater in PAT (1.72 +/- 0.13 nM) and kidney-transplantation (2.15 +/- 0.33 nM) patients than in healthy control subjects (0.50 +/- 0.10 nM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine, Ohio State University Hospitals, Columbus.
K
K
Osei
M L
ML
Henry
T M
TM
O'Dorisio
R J
RJ
Tesi
B G
BG
Sommer
R M
RM
Ferguson
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery*; D005260:Female; D005934:Glucagon; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000379:methods / Q000502:physiology*; D012016:Reference Values; D014184:Transplantation, Homologous
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005934:Glucagon