Respiration and phosphorylation of mitochondria isolated from the skeletal muscle of diabetic and normal subjects (original) (raw)

Summary

A group of diabetics, well controlled as far as blood sugar, free fatty acids and acetoacetate were concerned but with a high frequency of diabetic angiopathy in different organs, was compared with a group of controls in terms of the respiration and phosphorylation reactions in mitochondria isolated from skeletal muscle. Two keto-acidotic patients were also studied. The reactions studied were: respiration with glutamate or pyruvate plus malate as substrates, and also ratios of esterified inorganic orthophosphate to oxygen consumed and respiratory control with these substrates. The respiratory control in the absence of adenosine triphosphate was measured for pyruvate plus malate, and also the influence of serum albumin on this. Adenosine triphosphatase was measured under basal conditions and after maximal activation with 2,4-dinitrophenol. No certain differences were found between the non-ketotic diabetics and controls. Caution must be exercised in the interpretation of certain of the results because of difficulties in standardization of the mitochondrial isolation procedure in a patient material with wide ranges of age, infiltration of fibrous material in muscles, atrophy of muscles and other factors.

Résumé

Un groupe de diabétiques, bien contrôlés au point de vue de la glycémie, des acides gras et de l'acétoacétate, mais fréquemment porteurs d'angiopathie diabétique dans différents organes, a été comparé à un groupe de témoins en ce qui concerne les réactions de respiration et de phosphorylation dans les mitochondries isolées du muscle du squelette. Deux patients céto-acidosiques ont été également étudiés. Les réactions étudiées étaient: la respiration en présence de glutamate ou de pyruvate plus malate en tant que substrats, et également les rapports de l'orthophosphate inorganique estérifié sur l'oxygène consommé et le contrôle respiratoire avec ces substrats. Le contrôle respiratoire en l'absence d'adénosine triphosphate était mesuré pour le pyruvate plus malate et aussi l'influence de la sérum-albumine. L'activité adénosine triphosphatasique était mesurée dans des conditions basales et après une activation maximale avec du 2,4-dinitrophénol. Aucune différence certaine n'a été trouvée entre les diabétiques non-cétosiques et les témoins. On doit interpréter avec prudence certains résultats en raison des difficultés de standardisation des procédés d'isolement des mitochondries dans des prélèvements tissulaires effectués sur des patients d'âge très différent, présentant une infiltration fibreuse des muscles, de l'atrophie des muscles, ainsi que d'autres facteurs.

Zusammenfassung

Bei einer Gruppe von Diabetikern, deren Stoffwechsel auf Grund der Bestimmungen des Blutzuckers, der freien Fettsäuren und der Acetessigsäure gut eingestellt war, die aber in verstärktem Maße diabetische Gefäßerkrankungen in verschiedenen Organen aufwiesen, wurde im Vergleich zu einer Kontrollgruppe die Atmung und Phosphorylierung in isolierten Mitochondrien von Skeletmuskeln gemessen. Außerdem wurden 2 keto-acidotische Patienten untersucht. Im einzelnen bestimmten wir: Die Atmung mit Pyruvat oder Glutamat plus Malat als Substrat, ferner das Verhältnis von esterifiziertem, anorganischem Orthophosphat zum Sauerstoffverbrauch und die Kontrolle der Atmung bei diesen Substraten. Der Einfluß den Serum-Albumin auf die Atmungskontrolle ausübte, und diese selbst wurden in Abwesenheit von ATP und in Gegenwart von Pyruvat und Malat gemessen. Die Aktivität der ATPase wurde unter Ausgangsbedingungen und nach stärkster Stimulierung durch 2,4-Dinitrophenol bestimmt. Zwischen den Kontrollpersonen und nicht ketoacidotischen Diabetikern ergaben sich keine sicheren Unterschiede. Ein Teil der Ergebnisse muß allerdings besonders vorsichtig interpretiert werden, da das Isolierungsverfahren für die Mitochondrien nur schwer zu standardisieren ist, weil im Patientengut sehr starke Schwankungen in bezug auf Alter, Bindegewebseinlagerung in die Muskulatur, Muskelatrophie und andere Faktoren bestehen.

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Authors and Affiliations

  1. First Medical and Second Surgical Services, Sahlgrenska sjukhuset, University of Göteborg, Göteborg, Sweden
    Per Björntorp, Tore Scherstén & Sven -Erik Fagerberg

Authors

  1. Per Björntorp
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  2. Tore Scherstén
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  3. Sven -Erik Fagerberg
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Additional information

Reported briefly at the Fifth Congress of International Diabetes Federation, Toronto, Canada, July 23, 1964.

Reported at the Meeting of the Scandinavian Association for Diabetes Mellitus Research in Helsingör, Denmark, December 12, 1964.

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Björntorp, P., Scherstén, T. & Fagerberg, S.E. Respiration and phosphorylation of mitochondria isolated from the skeletal muscle of diabetic and normal subjects.Diabetologia 3, 346–352 (1967). https://doi.org/10.1007/BF00429867

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