Insulin inhibition and antagonism

Segal, Barry M.

doi:10.1016/0026-0495(64)90021-6

Cited by 9 publications

(1 citation statement)

References 64 publications

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“…Although many insulin antagonists have been demonstrated, 9 the one associated with albumin 10 has several characteristics which indicate its possible importance in the pathogenesis of human heredofamilial diabetes. It is present in higher concentrations in untreated diabetics than normal controls, 11 dependent on an intact pituitary gland, 12 and is active against insulin effects on muscle but not adipose tissue.…”

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confidence: 98%

Studies on the Mechanism of Insulin Antagonism by Albumin in Rat Diaphragm

Davidson

Goodner

1966

Diabetes

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Utilizing a modification of the rat diaphragm technic, studies of the mechanism of action of the albumin-associated antagonist were carried out using human fraction V. It was demonstrated that the antagonist could not be washed off of the diaphragm, that prior exposure of the diaphragm to insulin did not fully protect it from subsequent antagonism of the insulin effect and that, although antagonism was proportional to albumin concentration, large excesses of insulin could not completely overcome small concentrations of the antagonist. The intracellular accumulation of AIB was inhibited by the antagonistic albumin but not by a nonantagonistic one (bovine fraction V). Both albumins depressed radioactive glycine incorporation into muscle protein. The antagonist was shown to inhibit glucose uptake much more than glycogen synthesis.These data indicate that the albumin-associated antagonist primarily blocks insulin effects on transport by either an extremely strong binding to the muscle cell or an irreversible alteration of the diaphragm's response to insulin without binding. DIABETES J5: 373-79, June, 1966. Factors extraneous to the pancreas were first implicated in the pathogenesis of diabetes mellitus by the classical experiments of Houssay and Biasotti 1 who were able to produce an amelioration of the diabetic state by hypophysectomy in dogs. The demonstration that adrenalectomy also alleviates the severe diabetes caused by total pancreatectomy soon followed. 2 ' 3 When purified growth hormone became available, diabetes mellitus could be produced in normal cats 4 and dogs 5 by administration of this hormone. More recent evidence has been the demonstration of increased levels of circulating insulin in untreated adult-onset and early cases of juvenile diabetes by immunoassay, 6 rat diaphragm' 1 ' and adipose tissue 8 assays. All of this suggests From the Robert H.

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confidence: 98%