Insulin B chain-degrading neutral peptidase activity in the rat. Tissue distribution and the effects of starvation and streptozotocin-induced diabetes

Phelps, Bruce H.; Varandani, Partab T.; Shroyer, Lois A.

doi:10.1016/0003-9861(79)90321-7

Cited by 8 publications

(5 citation statements)

References 41 publications

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“…In agreement with prior biochemical and molecular studies (22)(23)(24)(25)(26), this work has shown by in situ hybridization that IDE gene expression is very widespread and is detected in most tissues in both the perinatal and adult rat. Likewise, the expression of either IR or IGFR is virtually universal in rat tissues, consistent with the fundamental role ofthese hormones in cellular metabolism and growth.…”

Section: Discussionsupporting

confidence: 92%

“…To further elucidate the possible functions of this enzyme and to evaluate its anatomical correlation with sites of insulin and IGF action and presumably also hydrolysis, this study was undertaken to localize the mRNAs encoding IDE, insulin, and IGF-I receptors (IGF) in serial sections by in situ hybridization. Prior studies have analyzed the levels of IDE protein by enzyme assays (22), crosslinking with labeled insulin (23), radioimmunoassays (24), and immunocytochemical localization (25). The localization of IDE mRNA has previously been investigated by Northern blot analyses and by ribonuclease protection assay (25,26).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cellular distribution of insulin-degrading enzyme gene expression. Comparison with insulin and insulin-like growth factor receptors.

Bondy¹,

Zhou²,

Chin³

et al. 1994

J. Clin. Invest.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Cellular distribution of insulin-degrading enzyme gene expression. Comparison with insulin and insulin-like growth factor receptors.

Bondy¹,

Zhou²,

Chin³

et al. 1994

J. Clin. Invest.

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“…199 tidase from rat kidney that degrades the insulin B-chain, purified by Varandani & Shroyer (1977) has weak or no activity towards proteins (denatured haemoglobin, albumin, insulin, ribonuclease) and a pH optimum of 6.5. This enzyme is reportedly inhibited by phosphate (Phelps et al, 1979). The inhibition by phosphate may, however, by a consequence of high ionic strength, as it can be calculated that the inclusion of 0.5 M-potassium phosphate in the assay was sufficient to raise the ionic strength from approx.…”

Section: Discussionmentioning

confidence: 99%

“…A specific phosphate effect may therefore be unlikely in view of the results described here. Another difference between the rat and mouse metallopeptidase is that the rat kidney activity decreases in response to diabetes (Phelps et al, 1979), whereas the mouse kidney activity is not affected by the disease (Bond, 1980). (3) The metallo-endopeptidase from rat kidney that preferentially hydrolyses parathyrin, described by Maruyama et al (1970), has some activity towards protein substrates but, in contrast with the Table 3.…”

Section: Discussionmentioning

confidence: 99%

Purification and characterization of a metallo-endoproteinase from mouse kidney

Beynon¹,

Shannon²,

Bond³

1981

Biochemical Journal

138

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A metallo-endoproteinase was purified from mouse kidney. The enzyme was solubilized from the 100 000 g sediment of kidney homogenates with toluene and trypsin, and further purified by fractionation with (NH4)2SO4. DEAE-cellulose chromatography and gel filtration. The molecular weight of the metalloproteinase was estimated by gel filtration on Sepharose 6B to be 270 000--320 000. On sodium dodecyl sulphate/polyacrylamide-gel electrophoresis in the presence of 2-mercaptoethanol, a single major protein with a mol.wt. of 81 000 was observed. Thus the active enzyme is an oligomer, probably a tetramer. It is a glycoprotein and has an apparent isoelectric point of 4.3. Kidney homogenates and purified preparations of the metalloproteinase degraded azocasein optimally at pH 9.5 and at I 0.15--0.2. The activity was not affected by inhibitors of serine proteinases (di-isopropyl phosphorofluoridate, phenylmethanesulphonyl fluoride), cysteine proteinases (4-hydroxymercuribenzoate, iodoacetate), aspartic proteinases (pepstatin) or several other proteinase inhibitors from actinomycetes (leupeptin, antipain and phosphoramidon). Inhibition of the enzyme was observed with metal chelators (EDTA, EGTA, 1,10-phenanthroline), and thiol compounds (cysteine, glutathione, dithioerythritol, 2-mercaptoethanol). The metalloproteinase degraded azocasein, azocoll, casein, haemoglobulin and aldolase, but showed little or no activity against the synthetic substrates benzoylarginine 2-naphthylamide, benzoylglycylarginine, benzyloxycarbonylglutamyltyrosine or acetylphenylalanyl 2-naphthyl ester. This metalloproteinase from mouse kidney appears to be distinct from previously described kidney proteinases.

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“…Such a distribution of radioactivity could be explained as resulting from a process responsible for insulin degradation and inactivation. Thus studies to date suggest that the metabolism of insulin in a variety of tissues proceeds initially by a reductive cleavage into the A-and B-chains followed by extensive proteolytic cleavage of the separated chains (Brush, 1971;Chandler & Varandani, 1975;Phelps et al, 1979). However, it is conceivable that the metabolism of insulin may be an important component of the mechanism of action of the hormone (Steiner, 1977;Goldfine, 1978) and that an initial cleavage into A-and B-chains is part of this process.…”

Section: Discussionmentioning

confidence: 99%

Prolonged effect of insulin on glucose uptake by rat skeletal muscle

Lewis

Schultz

Daniels

et al. 1980

Biochemical Journal

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The fate of insulin, as it relates to its action on skeletal-muscle glucose uptake, was studied in non-cyclically perfused rat hindlimbs. Insulin (1m-i.u./ml) with and without (125)I-labelled insulin was infused intra-arterially for 5 or 6min. Net glucose uptake and the release of (125)I-labelled insulin into the venous effluent were evaluated by arteriovenous-difference measurements for an additional 24-32min. The infusion of insulin for 5min promoted glucose uptake, an effect that persisted throughout a subsequent 25min of perfusion in the absence of insulin. The addition of insulin antibody to the perfusate in the presence of insulin blocked the action of insulin on glucose uptake, but it failed to alter insulin action if the muscle tissue had been exposed to insulin before addition of antibody. When (125)I-labelled albumin was infused for 6min, venous effluent radioactivity decayed rapidly and remained HClO(4)-insoluble and there was no significant tissue retension of radioactivity. Comparable experiments in which (125)I-labelled insulin was infused for 6min revealed that the venous effluent radioactivity decayed more slowly, a significant amount of the (125)I-labelled insulin appeared as fragments (HClO(4)-soluble) and there was a significant retention of radioactivity in the tissue. Radioactivity in muscle tissue biopsies obtained 28min after infusion of (125)I-labelled insulin was associated largely with intact insulin and a peptide of mol.wt. 2400. The total radioactivity retained in the muscle at this time was 7% of the amount infused. An insulin bolus (1i.u.) failed to increase the discharge of this tissue-associated radioactivity. These results suggest that insulin and a product of insulin metabolism persists in muscle tissue long after the arterial presence of insulin ends. This tissue residence and processing of insulin may be important components of insulin's prolonged action on glucose uptake by skeletal muscle.

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Insulin B chain-degrading neutral peptidase activity in the rat. Tissue distribution and the effects of starvation and streptozotocin-induced diabetes

Cited by 8 publications

References 41 publications

Cellular distribution of insulin-degrading enzyme gene expression. Comparison with insulin and insulin-like growth factor receptors.

Cellular distribution of insulin-degrading enzyme gene expression. Comparison with insulin and insulin-like growth factor receptors.

Purification and characterization of a metallo-endoproteinase from mouse kidney

Prolonged effect of insulin on glucose uptake by rat skeletal muscle

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