TY - JOUR
T1 - Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus
AU - Luzi, Livio
AU - Hering, Bernhard J.
AU - Socci, Carlo
AU - Raptis, George
AU - Battezzati, Alberto
AU - Terruzzi, Ileana
AU - Falqui, Luca
AU - Brandhorst, Heide
AU - Brandhorst, Daniel
AU - Regalia, Enrico
AU - Brambilla, Eugenia
AU - Secchi, Antonio
AU - Perseghin, Gianluca
AU - Maffi, Paola
AU - Bianchi, Elda
AU - Mazzaferro, Vincenzo
AU - Gennari, Leandro
AU - Di Carlo, Valerio
AU - Federlin, Konrad
AU - Pozza, Guido
AU - Bretzel, Reinhard G.
PY - 1996/6/1
Y1 - 1996/6/1
N2 - The intraportal injection of human pancreatic islets has been indicated as a possible alternative to the pancreas transplant in insulin-dependent diabetic patients. Aim of the present work was to study the effect of intraportal injection of purified human islets on: (a) the basal hepatic glucose production; (b) the whole body glucose homeostasis and insulin action; and (c) the regulation of insulin secretion in insulin-dependent diabetes mellitus patients bearing a kidney transplant. 15 recipients of purified islets from cadaver donors (intraportal injection) were studied by means of the infusion of labeled glucose to quantify the hepatic glucose production. Islet transplanted patients were subdivided in two groups based on graft function and underwent: (a) a 120-min euglycemic insulin infusion (1 mU/kg/min) to assess insulin action; (b) a 120-min glucose infusion (+75 mg/dl) to study the pattern of insulin secretion. Seven patients with chronic uveitis on the same immunosuppressive therapy as grafted patients, twelve healthy volunteers, and seven insulin-dependent diabetic patients with combined pancreas and kidney transplantation were also studied as control groups. Islet transplanted patients have: (a) a higher basal hepatic glucose production (HGP: 5.1±1.4 mg/kg/min; P <0.05 with respect to all other groups) if without graft function, and a normal HGP (2.4±0.2 mg/kg/min) with a functioning graft; (b) a defective tissue glucose disposal (3.9±0.5 mg/kg/min in patients without islet function and 5.3±0.4 mg/kg/min in patients with islet function) with respect to normals (P <0.01 for both comparisons); (c) a blunted first phase insulin peak and a similar second phase secretion with respect to controls. In conclusion, in spite of the persistence of an abnormal pattern of insulin secretion, successful intraportal islet graft normalizes the basal HGP and improves total tissue glucose disposal in insulin-dependent diabetes mellitus.
AB - The intraportal injection of human pancreatic islets has been indicated as a possible alternative to the pancreas transplant in insulin-dependent diabetic patients. Aim of the present work was to study the effect of intraportal injection of purified human islets on: (a) the basal hepatic glucose production; (b) the whole body glucose homeostasis and insulin action; and (c) the regulation of insulin secretion in insulin-dependent diabetes mellitus patients bearing a kidney transplant. 15 recipients of purified islets from cadaver donors (intraportal injection) were studied by means of the infusion of labeled glucose to quantify the hepatic glucose production. Islet transplanted patients were subdivided in two groups based on graft function and underwent: (a) a 120-min euglycemic insulin infusion (1 mU/kg/min) to assess insulin action; (b) a 120-min glucose infusion (+75 mg/dl) to study the pattern of insulin secretion. Seven patients with chronic uveitis on the same immunosuppressive therapy as grafted patients, twelve healthy volunteers, and seven insulin-dependent diabetic patients with combined pancreas and kidney transplantation were also studied as control groups. Islet transplanted patients have: (a) a higher basal hepatic glucose production (HGP: 5.1±1.4 mg/kg/min; P <0.05 with respect to all other groups) if without graft function, and a normal HGP (2.4±0.2 mg/kg/min) with a functioning graft; (b) a defective tissue glucose disposal (3.9±0.5 mg/kg/min in patients without islet function and 5.3±0.4 mg/kg/min in patients with islet function) with respect to normals (P <0.01 for both comparisons); (c) a blunted first phase insulin peak and a similar second phase secretion with respect to controls. In conclusion, in spite of the persistence of an abnormal pattern of insulin secretion, successful intraportal islet graft normalizes the basal HGP and improves total tissue glucose disposal in insulin-dependent diabetes mellitus.
KW - glucose metabolism
KW - hepatic glucose production
KW - immunosuppressive therapy
KW - insulin resistance
KW - islet secretion
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M3 - Article
C2 - 8647955
AN - SCOPUS:8944251633
VL - 97
SP - 2611
EP - 2618
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 11
ER -