Reduction of cardiovascular and thyroxine-suppressing activities of L-T3 by liver targeting with cholic acid

Stephan, Zouhair F.; Yurachek, E.C.; Sharif, Robin; Wasvary, Jong M.; Steele, Ronald E.; Howes, Colin

doi:10.1016/0006-2952(92)90640-5

Cited by 44 publications

(13 citation statements)

References 28 publications

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“…4) (reviewed by Kramer and Wess, 1996). Moreover, a desired low-density lipoprotein receptor upregulating activity of thyroid hormones in hepatocytes was attained by conjugating L-triiodothyronine to CA (Stephan et al, 1992).…”

Section: Bile Acid Transporter As a Target For Deliverymentioning

confidence: 98%

Transporters for Bile Acids and Organic Anions

Suzuki

Sugiyama

2002

Pharmaceutical Biotechnology

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Section: Bile Acid Transporter As a Target For Deliverymentioning

confidence: 98%

Transporters for Bile Acids and Organic Anions

Suzuki

Sugiyama

2002

Pharmaceutical Biotechnology

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“…The mechanism likely involves a liverselective uptake, as L-94901 binds both TRs with similar affinity. CGH 509A, the conjugation of the primary bile acid cholic acid to L-triiodothyronine, has been evaluated as to gain a preferential liver uptake (Stephan et al, 1992). CGH 509A was able to reduce serum cholesterol in rats, although it is less potent than L-T 3 alone, without adverse effects on heart or T 4 lowering (Stephan et al, 1992).…”

Section: Selective Thyroid Hormone Receptor Modulatorsmentioning

confidence: 99%

Nuclear Receptors and Their Selective Pharmacologic Modulators

Burris

Solt

Wang

et al. 2013

Pharmacological Reviews

229

205

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“…(iii) Direct conjugation to the C 24 carboxyl group of cholic acid has been undertaken with triiodothyronine, though the purpose in this case was to reduce the uptake by the heart since triiodothyronine is already absorbable from the small intestine [77]. Successful absorption of a carbohydrate molecule in the form of heparin which was conjugated at an amine group to the C 24 carboxyl group of deoxycholic acid has also been reported [78].…”

Section: Absorption Of Covalently-bonded Insulinmentioning

confidence: 99%

Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat

McGinn¹,

Morrison

2016

Journal of Controlled Release

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Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat. Journal of Controlled Release, 232, pp. 120-130. (doi:10.1016Release, 232, pp. 120-130. (doi:10. /j.jconrel.2016 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/120651/ ABSTRACTExperiments have been undertaken to determine the extent to which cholic acid conjugates of insulin were absorbed from the small intestine of anaesthetised rats by means of the bile salt transporters of the ileum. The measure used to assess the absorption of the cholyl-insulins was the amount of hypoglycaemia following infusion into the small intestine. Control experiments involving infusion of natural insulin into the ileum showed either nil absorption or absorption of a small amount of insulin as indicated by transient dip in the blood glucose concentration. However, when insulin was co-infused with the bile salt taurocholate, this was followed by a marked hypoglycaemic response which was specific to the ileum and did not occur on infusion into the jejunum. When the two cholyl conjugates of insulin were tested viz. B 29 -Lys-cholyl-insulin and B 1 -Phe-cholyl-insulin, both were biologically active as indicated by hypoglycaemic responses on systemic injection, though their potency was about 40% of that of natural insulin. While there was no evidence for the absorption of B 29 -Lys-cholyl-insulin when infused into the ileum, B 1 -Phe-cholyl-insulin did cause a long lasting hypoglycaemic response, indicating that absorption had occurred. Since the hypoglycaemic response was blocked on co-infusion with taurocholate and was absent for infusion of the conjugate into the jejunum, these results were taken as evidence that B 1 -Phe-cholyl-insulin had been taken up by the ileal bile salt transporters. This would indicate that B 1 -Phe-cholyl-insulin is worthy of further investigation for use in an oral insulin formulation.

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Reduction of cardiovascular and thyroxine-suppressing activities of L-T3 by liver targeting with cholic acid

Cited by 44 publications

References 28 publications

Transporters for Bile Acids and Organic Anions

Transporters for Bile Acids and Organic Anions

Nuclear Receptors and Their Selective Pharmacologic Modulators

Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat

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