Regulation of multicatalytic enzyme activity by insulin and the insulin- degrading enzyme

Frederick G Hamel, Robert G Bennett, William C. Duckworth

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The insulin-degrading enzyme (IDE) plays an important role in the cellular metabolism of insulin. Recent studies have also suggested a regulatory role for this protein in controlling the activity of cytoplasmic protein complexes, including the proteasome [multicatalytic proteinase (MCP)] and the glucocorticoid and androgen receptors. Binding of IDE to these complexes increases their activity, whereas the addition of substrates for IDE inhibits activity. This provides a potential mechanism of action for internalized insulin and other IDE substrates in the control of protein turnover. To examine further the interactions, partially purified IDE-MCP complex was treated with EDTA or EGTA, and activity was measured in the absence and presence of various divalent cations (Ca2+, Mn2+, Co2+, and Zn2+) and insulin. EDTA treatment reduced MCP activity and eliminated the effect of insulin on the complex. Divalent cations partially or completely restored MCP activity, but did not restore the effect of insulin. EGTA treatment had a lesser effect on MCP activity, but abolished insulin inhibition of activity. Divalent cations restored the insulin effect. Inhibitors of IDE also blocked the insulin effect on MCP activity, as did treatment with SDS. These findings suggest that conformational changes in the complex may play a role in the insulin control of MCP activity.

Original languageEnglish (US)
Pages (from-to)4061-4066
Number of pages6
JournalEndocrinology
Volume139
Issue number10
DOIs
StatePublished - Jan 1 1998

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Insulysin
Proteasome Endopeptidase Complex
Insulin
Enzymes
Divalent Cations
Egtazic Acid
Edetic Acid
Proteins
Glucocorticoid Receptors
Androgen Receptors
Action Potentials

ASJC Scopus subject areas

  • Endocrinology

Cite this

Regulation of multicatalytic enzyme activity by insulin and the insulin- degrading enzyme. / Hamel, Frederick G; Bennett, Robert G; Duckworth, William C.

In: Endocrinology, Vol. 139, No. 10, 01.01.1998, p. 4061-4066.

Research output: Contribution to journalArticle

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