Degradation products of insulin generated by hepatocytes and by insulin protease.

Wc, Duckworth; Hamel, Frederick G.; Peavy, Daniel E.; Liepnieks, Juris J.; Ryan, Michael P.; Hermodson, Mark A.; Frank, Bruce H.

doi:10.1016/s0021-9258(19)77951-4

Cited by 94 publications

(30 citation statements)

References 37 publications

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“…Although the biochemical properties of the mammalian IDE have been studied extensively, the enzyme has been characterized primarily as a specific degrading enzyme for insulin and insulin-related factors (5,25). We now report a novel property of the mammalian enzyme-the ability to bind and degrade TGF-alpha.…”

Section: Discussionmentioning

confidence: 92%

“…Results of the analysis of insulin cleavage suggest that both the Drosophila enzyme and its mammalian counterpart display conformational rather than peptide bond specificity (5,6). The Drosophila enzyme cleaves a subset of the insulin bonds that are cleaved by the mammalian IDE (5,6), a further indication of the evolutionary conservation of the enzyme's substrate specificity. We have also demonstrated previously (8) that the Drosophila enzyme binds and cross-links to insulin and EGF-related factors, but not to TGF-beta, PDGF, nerve growth factor, adrenocorticotropic hormone, or parathyroid hormone.…”

Section: Discussionmentioning

confidence: 99%

“…As a degrading enzyme, the IDE has an unusual substrate specificity. Results of the analysis of insulin cleavage suggest that both the Drosophila enzyme and its mammalian counterpart display conformational rather than peptide bond specificity (5,6). The Drosophila enzyme cleaves a subset of the insulin bonds that are cleaved by the mammalian IDE (5,6), a further indication of the evolutionary conservation of the enzyme's substrate specificity.…”

Section: Discussionmentioning

confidence: 99%

“…Less is known about the degradation of TGF-alpha. By contrast, the insulin-degrading enzyme ODE) has been well characterized as the enzyme responsible for initiating insulin degradation in mammalian cells (5,12,23).…”

mentioning

confidence: 99%

“…richia colt protease (1). Because of their similarities and the fact that both the mammalian and Drosophila enzymes cleave porcine insulin at the same major sites (5,6,12), we have termed our protein the Drosophila IDE. Furthermore, antigenic, physical, and kinetic properties indicate that the Drosophila IDE is identical to a previously characterized Drosophila growth factor-binding protein (8,28).…”

mentioning

confidence: 99%

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An evolutionarily conserved enzyme degrades transforming growth factor-alpha as well as insulin.

Garcia

Gehm

Rosner

1989

The Journal of Cell Biology

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Abstract. A single enzyme found in both Drosophilaand mammalian cells is able to selectively bind and degrade transforming growth factor (TGF)-alpha and insulin, but not EGF, at physiological concentrations. These growth factors are also able to inhibit binding and degradation of one another by the enzyme. Although there are significant immunological differences between the mammalian and Drosophila enzymes, the substrate specificity has been highly conserved. These results demonstrate the existence of a selective TGFalpha-degrading enzyme in both Drosophila and mammalian cells. The evolutionary conservation of the ability to degrade both insulin and TGF-alpha suggests that this property is important for the physiological role of the enzyme and its potential for regulating growth factor levels.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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An evolutionarily conserved enzyme degrades transforming growth factor-alpha as well as insulin.

Garcia

Gehm

Rosner

1989

The Journal of Cell Biology

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Prolonged elevation of insulin content in the unicellular tetrahymena after insulin treatment: induction of insulin production or storage?

Csaba

Gaál

Kovács

et al. 1999

Cell Biochem. Funct.

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In the unicellular organism, Tetrahymena, the ®rst encounter with an exogeneously given hormone results in hormonal imprinting. This causes an increase of the binding capacity of receptors and the production of the appropriate hormone in the progeny generations of the treated cell. In the present experiments the quantity (using radioimmunoassay) and localization (using confocal laser scanning microscopy) of the immunologically insulin-like material (hereafter insulin) were studied for 10 days after 4 h or 24 h 10 À6 M insulin treatment (hormonal imprinting). Forty-eight hours after both insulin treatments a high quantity of insulin was present in the cells. This value was also signi®cantly increased after 96 h. After 8 days the dierence to the control was signi®cant only in the 24 h treated group. Confocal microscopy (using antibody to pig insulin) localized insulin in the cell body. The oral ®eld contained extremely high quantities of the endogeneous hormone. Insulin treatment (after 48 and 96 h) caused an elevation of insulin content in general, and speci®c accumulation in the posterior sections of the cell, around the nucleus and in the periphery were observed. Ten days after both treatments only the peripheral region of the cell body and the ciliary row contained more insulin than the control. This means that after insulin treatment the quantity of insulin increases for a lengthy time period which is followed by the expression of insulin in the peripheral region. Insulin contained by Tetrahymena 48 h after imprinting stimulated glucose uptake of rat diaphragm.

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Pitrilysins/Inverzincins

Maskos

2004

Handbook of Metalloproteins

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Inverzincins are characterized by an inverted zinc‐binding motif (HxxEH) rather than the classical zincin motif (HExxH). Pitrilysin from Escherichia coli is the prototype of one subfamily, which also contains eukaryotic family members such as the insulin‐degrading enzyme (IDE) and the N ‐arginine dibasic convertase (NRDc), both playing important roles in hormone metabolism and cellular regulation. The topology of active site residues shows some similarity to zincins, suggesting a convergent evolution for these types of metalloproteases. The closely related members of the mitochondrial processing peptidase (MPP) subfamily function as soluble heterodimers or as building blocks of the cytochrome c reductase complex and share the tendency with pitrilysin‐like enzymes to cleave peptides at hydrophobic or positively charged sites in a context‐dependent manner. For several family members, binding and cleavage of substrate is supposed to depend on secondary or tertiary structure and seems to proceed within a compartment formed by the respective enzyme.

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Degradation products of insulin generated by hepatocytes and by insulin protease.

Cited by 94 publications

References 37 publications

An evolutionarily conserved enzyme degrades transforming growth factor-alpha as well as insulin.

An evolutionarily conserved enzyme degrades transforming growth factor-alpha as well as insulin.

Prolonged elevation of insulin content in the unicellular tetrahymena after insulin treatment: induction of insulin production or storage?

Pitrilysins/Inverzincins

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