Abstract
The abnormal glucose tolerance seen in experimental diabetic animals receiving pancreatic transplants has been assumed to be due to a reduced functional islet mass.
Collagenase-dispersed autografts were prepared following total pancreatectomy. Six dogs received 100%, and 6 received 50% of the tissue so formed. Blood glucose, lactate, pyruvate, alanine, glycerol, 3-hydroxybutyrate, cholesterol, free fatty acids, insulin, glucagon, and cortisol were determined in the fasting state and following an intravenous glucose load (IVGTT). Glucose clearance (K) was calculated. Fasting euglycemia was achieved and insulin levels were the same in both groups. Similar reductions in K, with elevated fasting levels of glycerol, and 3-hydroxybutyrate, were present in both groups 1 month after transplantation. Glucose-stimulated insulin output was both quantitatively and qualitatively defective with similar levels being achieved in peripheral blood in both groups. This abnormal insulin response exposed elevated levels of free fatty acids and alanine during the IVGTT, although suppression of glucagon was normal in both groups.
The results suggest that a simple relationship between transplant mass and insulin secretion does not exist. This may be important in regard to the future clinical application of free transplantation in the treatment of diabetes.
Résumé
La tolérance anormale au glucose constatée chez les animaux diabétiques transplantés a été attribués à une diminution de la fonction de la masse insulaire.
Les autogreffes d'éléments insulaires isolés avaient été préparées après pancréatectomie totale. Six chiens en reçurent la totalité et six la moitié. Le dosage des éléments suivants: glucose, lactate, pyruvate, alanine, glycérol, 3-hydroxyburate, cholestérol, acides gras libres, insuline, glucagon et cortisol a été pratiqué à jeun et après administration intraveineuse d'une quantité déterminée de glucose. La clairance du glucose (K) a été déterminée. L'euglycémie à jeun fut atteinte et les taux d'insuline furent identiques chez les deux groupes d'animaux. Des réductions identiques de la clairance du glucose avec une élévation à jeun du glycérol, du 3-hydroxybutyrate furent constatées dans les deux groupes un mois après la transplantation. Le débit insulinique stimulé par le glucose fut à la fois anormal quantitativement et qualitativement, des taux identiques étant atteints au niveau du sang périphérique dans les deux groupes. Cette réponse insulinique anormale dévoila une augmentation des taux des acides gras libres et de l'alanine lors de la surchage intraveineuse de glucose, bien que la suppression du glucagon fût normale dans les deux groupes.
Ces résultats suggèrent qu'une relation simple entre la masse transplantée et la sécrétion insulinique n'existe pas. Ce fait peut être important quand on considère l'application clinique de la transplantation insulaire pour traiter le diabète.
Resumen
Se ha asumido que la anormal tolerancia a la glucosa que se observa en animales experimentales diabéticos recipientes de transplantes pancreáticos se debe a una reducida masa funcional de islotes. El propósito del presente estudio fue el de determinar la factibilidad de producir dos transplantes de un solo páncreas canino y valorar la relación que pudiera existir entre la masa de islotes implantada y su función metabólica.
Se prepararon autotransplantes digeridos por colagenasa después de realizada la pancreatectomia. Seis perros recibieron el 100% y seis el 50% de los tejidos así preparados.
Glucosa sanguínea, lactato, piruvato, alanina, glicerol, 3-hidroxibutirato, colesterol, ácidos grasos libres, insulina, glucagón y cortisol fueron determinados en ayunas y después de una carga de glucosa intravenosa. También se calculó la depuración de glucosa (K).
Se observó euglicemia en ayunas junto con iguales niveles de insulina en los dos grupos de perros. Reducciones similares de K con elevados niveles, en ayunas, de glicerol y de 3-hidroxibutirato fueron aparentes en ambos grupos un mes después del transplante. La secreción de insulina estimulada por glucosa apareció tanto cuantitativa como cualitativamente defectuosa, con niveles similares en la sangre periférica en ambos grupos. Esta respuesta insulínica anormal expuso altos niveles de ácidos grasos libres y de alanina en el curso de la prueba de tolerancia a la carga de glucosa intravenosa, aún cuando la supresión del glucagón apareció normal en los dos grupos.
Los resultados sugieren que no existe una relación simple entre la masa del transplante y la secreción de insulina. Este puede ser un hecho de importancia en relación a la futura aplicación clínica de los transplantes libres en el tratamiento de la diabetes.
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Supported by the Wellcome Trust and Newcastle Health Authority (Scientific and Research Committee).
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Alderson, D., Farndon, J.R. The effects of transplant mass on insulin release by collagenase-dispersed pancreatic fragments in the diabetic dog. World J. Surg. 8, 598–602 (1984). https://doi.org/10.1007/BF01654946
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DOI: https://doi.org/10.1007/BF01654946