Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus

Livio Luzi; Bernhard J. Hering; Carlo Socci; George Raptis; Alberto Battezzati; Ileana Terruzzi; Luca Falqui; Heide Brandhorst; Daniel Brandhorst; Enrico Regalia; Eugenia Brambilla; Antonio Secchi; Gianluca Perseghin; Paola Maffi; Elda Bianchi; Vincenzo Mazzaferro; Leandro Gennari; Valerio Di Carlo; Konrad Federlin; Guido Pozza; Reinhard G. Bretzel

doi:10.1172/JCI118710

Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus

Livio Luzi, Bernhard J. Hering, Carlo Socci, George Raptis, Alberto Battezzati, Ileana Terruzzi, Luca Falqui, Heide Brandhorst, Daniel Brandhorst, Enrico Regalia, Eugenia Brambilla, Antonio Secchi, Gianluca Perseghin, Paola Maffi, Elda Bianchi, Vincenzo Mazzaferro, Leandro Gennari, Valerio Di Carlo, Konrad Federlin, Guido PozzaReinhard G. Bretzel

Surgery

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Abstract

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.

Original language	English (US)
Pages (from-to)	2611-2618
Number of pages	8
Journal	Journal of Clinical Investigation
Volume	97
Issue number	11
DOIs	https://doi.org/10.1172/JCI118710
State	Published - Jun 1 1996

Keywords

glucose metabolism
hepatic glucose production
immunosuppressive therapy
insulin resistance
islet secretion

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1172/JCI118710

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Luzi, L., Hering, B. J., Socci, C., Raptis, G., Battezzati, A., Terruzzi, I., Falqui, L., Brandhorst, H., Brandhorst, D., Regalia, E., Brambilla, E., Secchi, A., Perseghin, G., Maffi, P., Bianchi, E., Mazzaferro, V., Gennari, L., Di Carlo, V., Federlin, K., ... Bretzel, R. G. (1996). Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus. Journal of Clinical Investigation, 97(11), 2611-2618. https://doi.org/10.1172/JCI118710

Luzi, L, Hering, BJ, Socci, C, Raptis, G, Battezzati, A, Terruzzi, I, Falqui, L, Brandhorst, H, Brandhorst, D, Regalia, E, Brambilla, E, Secchi, A, Perseghin, G, Maffi, P, Bianchi, E, Mazzaferro, V, Gennari, L, Di Carlo, V, Federlin, K, Pozza, G & Bretzel, RG 1996, 'Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus', Journal of Clinical Investigation, vol. 97, no. 11, pp. 2611-2618. https://doi.org/10.1172/JCI118710

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abstract = "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.",

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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.

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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.

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KW - hepatic glucose production

KW - immunosuppressive therapy

KW - insulin resistance

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Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus

Abstract

Keywords

UN SDGs

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