Insulinase

Site of synthesis and secretion Enzyme that degrades insulin and its source Half-life of insulin Insulin is a polypeptide hormone produced by thep cells of the islets of Langerhans of the pancreas. Its synthesis involves two inactive precursors, preproinsulin and proinsulin, which are subsequently cleaved to form the active hormone. Insulin is stored in the cytosol in granules that are released by exocytosis Insulin is degraded by the enzyme insulinase produced primarily by the liver. Insulin has a plasma half-life of approximately six minutes. 

Substrates for hepatic metabolism include insulin, glucagon, and t-PAs [89,90]. For insulin, an acidic endopeptidase (termed endosomal acidic insulinase ) appears to mediate internalized insulin proteolysis at a number of sites [91]. Specifically, the endosomal activity results from cathepsin D, an aspartic acid protease [92]. Similarly, proteolysis of glucagon has also been attributed to membrane-bound forms ofcathepsins B and D [93]. 

Authier, F., G.M. Danielsen, M. Kouach, G. Briand, and G. Chauvet. 2001. Identification of insulin domains important for binding to and degradation by endosomal acidic insulinase. Endocrinology 142 276-289. 

Internalization of protein hormones is a principal means of hormone degradation in lysosomes through a receptor-mediated pathway [70], There may also be membrane-associated degradative activities for insulin (insulinase) and other protein hormones, however for EGF, degradation occurs exclusively through an intracellular process [68,71]. 

Study of the interrelationship between insulinase, diabetes mellitus, and tryptophan (M9) revealed that n-tryptophan, administered either subcutaneously or by stomach tube in the amount 1-lmM/kg, produces a statistically highly significant hypoglycemia in the rat, whereas D-tryptophan and 16 other amino acids were ineffective when given by mouth in similar doses. In contrast to the effect produced in normal rats, there is no hypoglycemic response in severely diabetic alloxanized rats given L-tryptophan. 

In view of the hypoglycemic and insulinase-inhibitory action of l-tryptophan, it seemed pertinent to Mirsky to study the effect of various metabolic products of tryptophan on the blood sugar of normal and diabetic rats (M9), A statistically significant hypoglycemic response was produced after oral administration of anthranilic acid, niacin, indole-3-acetic acid, 5-hydroxytryptophan, and serotonin. A hypoglycemic fol-... 

M9. Mirslcy, A., Insulinase, insulinase-inhibitors, and diabetes mellitus. Recent Progr. Hormone Res. 13, 429-471 (1957). 

The growing family of known divalent cation-dependent proteases such as insulinase [51] and dibasic convertase [52], with the variant consensus HxxeH, also present interesting questions as to the possibility of a mirrored active site with or without conservation of the overall topology. Conversely, it is possible that entirely different proteins which have no zinc dependency and completely separate function may adopt the zinc endoprotease topology, simply because this fold provides a stable modular scaffold useful in the construction of multidomain proteins. Results of further structural studies are eagerly awaited. 

Insulinase. An enzyme that hydrolyzes insulin and is prepd from hog pancreas Brink, Lewis, U.S. pet. 2,957, -809 (I960 to Merck Co.). May be obtained from commercial pancreatin or trypsin. Even the purified crystals contain large amounts of elastase. Review Thomas, Postgrad. Med. J. Suppl, 49, 940 (1973). 

Sapin, R., J-C. Ongagna, F. Gasser, and D. Grucker. 1998. Insulin measurements in hemolyzed serum Influence of insulinase inhibitors. Clinica ChimicaActa 274 111-117. 

The presence of a specific insulinase in the pancreas has often been claimed, but the preparations are too impure to permit definite conclusions. The insulinase preparation now available may well be a mixture of several proteolytic enzymes. The role of these enzymes, if any, in the pathogenesis of diabetes remains to be established. 

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