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Am J Pathol ; 183(5): 1527-38, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24160324

RESUMO

Islet transplantation is a poorly investigated long-term strategy for insulin replacement and for treatment of complications in patients with diabetes. We investigated whether islet transplantation and insulin treatment can relieve diabetic neuropathy and rescue the residual endogenous pancreatic ß cells. We used a multimodal approach, with five groups of Sprague-Dawley rats studied for 8 months: control rats, diabetic rats, insulin-treated diabetic rats with moderate or mild hyperglycemia, and diabetic rats transplanted with microencapsulated islets. Islet transplantation normalized glycemia and increased body and muscle weight; it was also effective in reducing proteinuria and altered liver function. Transplantation significantly improved tail nerve conduction velocity, Na(+)-K(+)-ATPase activity, and morphological alterations in the sciatic nerve as evidenced by decrease in g-ratio; it also restored thermal and ameliorated mechanical nociceptive thresholds. Morphometric analysis of pancreas indicated a significant ß-cell volume increase in transplanted rats, compared with mildly and moderately hyperglycemic rats. Thus, allogeneic islet transplantation had a positive systemic effect in diabetic rats and induced regression of the established neuropathy and restitution of the typical characteristics of the islets. These findings strongly reinforce the need for improving glycemic control, not only to reverse established diabetic complications but also to improve ß-cell status in diabetic pancreas.


Assuntos
Complicações do Diabetes/patologia , Complicações do Diabetes/terapia , Células Secretoras de Insulina/patologia , Insulina/administração & dosagem , Transplante das Ilhotas Pancreáticas , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Complicações do Diabetes/sangue , Complicações do Diabetes/fisiopatologia , Glucagon/metabolismo , Teste de Tolerância a Glucose , Hiperglicemia/complicações , Hiperglicemia/patologia , Insulina/farmacologia , Insulina/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/enzimologia , Masculino , Condução Nervosa/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Proteinúria/complicações , Proteinúria/patologia , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
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