Beta cell insulin synthesis

Blood sugar (blood glucose) in human beings is controlled by the secretion of (—>) insulin by the beta (B- or (3-) cells of the islands of Langerhans in the pancreas. Loss of insulin synthesis leads to (—>) diabetes. Type 1 diabetes (insulin dependent diabetes mellitus, EDDM) begins in juveniles as an organ-specific autoimmune reaction, the destructive insulitis. 

Aloe barbadensis Miller (Liliaceae) sym A. vera L A. vulgaris Lamk Leaves (Saudi Arabia) When Aloe barbadensis leaves extract was administered twice daily orally, reduction in blood glucose level of alloxan diabetic mice was observed. It was observed that hypoglycemic effect of aloes and its bitter principle may be mediated through stimulating synthesis and/ or release of insulin from beta-cells of Langerhans [121],... 

Insulin, Inutral Optisulin long. Polypeptide hormone produced in the beta cells of the islets of Laager-bans situated in the pancreas of all vertebrates. Synthesized in vivo via a single chain polypeptide precursor, proinsulin, native conformation has been established. Secreted directly into the bloodstream where it regulates carbohydrate metabolism, influences the synthesis of protein and of RNA, and the formation and storage of neutral lipids. The first protein for which chemical structure and precise mol wt were determined Sanger, Tuppy, Biochem. J. 49, 463, 481 (1951) ... 

On the basis of theoretical considerations, it had been su ested that the beta cell may have a low GSH content (44). The synthesis of insulin by the beta cell appears to be dependent upon a continuous supply of sulfur-amino acids, for when rabbits are placed on a cystine-methionine-deficient diet the insulin content of the pancreas is decreased (32). Insulin, in contrast to most other proteins, contains 12 % cystine (45). Since cysteine or its oxidized derivative, cystine, is a constituent of both GSH and of insulin, there may well be competition for this amino acid within the beta cell. Thus the GSH concentration within the beta cell may be low as a consequence of insulin synthesis (44). Furthermore, the oxidation-reduction potential in the beta cell may favor the oxidation of GSH to its oxidized form (GSSG) (44). Both of these factors would increase the susceptibility of the beta cells to alloxan, for it is the reduced form of GSH which reacts with alloxan (26). 

However, if the secondary drop in GSH level is associated with a corresponding decrease in the beta cell GSH, then this factor might well contribute to the progressive destruction of the beta cells which remain in the pancreatic remnant of the subtotally depancreatized animal or in the human subject with severe diabetes. Furthermore, one wonders whether the diminished tolerance to glucose, which is observed in the scorbutic guinea pig (50) or in the rabbit receiving repeated injections of acetoacetate (51), may likewise be due to a functional impairment of insulin synthesis, occurring as the result of a GSH depletion within the beta cell. 

In interpreting these facts we have suggested that alloxan may kill the beta cell because it reacts with glutathione or with some essential sulfhydryl enzyme within the beta cell and on the basis of theoretical considerations we have postulated that the selectivity of alloxan may be due to a low glutathione concentration writhin the beta cell, occurring as a consequence of its specialization for insulin synthesis (44). Alloxan does react with a number of sulfhydryl enzymes and we have recent evidence to show that alloxan also reacts with coenzyme A. 

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