Rat liver insulin mediator which stimulates pyruvate dehydrogenase phosphatase contains galactosamine and D-chiroinositol

Larner, Joseph; Huang, Laura C.; Schwartz, Charles; Oswald, Allison S.; Shen, T. Y.; Kinter, Michael; Tang, Ghouzi; Zeller, Konrad

doi:10.1016/s0006-291x(88)80520-5

Cited by 208 publications

(126 citation statements)

References 18 publications

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“…Mediator (20 To obtain further information on the components of the isolated bioactive fractions, nitrous acid exposure experiments were performed. Exposure of IPGs to nitrous acid results in deamination of non-N-acetylated hexosamines, with subsequent cleavage of adjacent glycosidic bonds (releasing inositol) and loss of bioactivity [3,4,6]. Freeze-dried samples were reconstituted with 50 mmol/l sodium acetate, pH 3.5 ± sodium nitrite (NaNO 2 ) and incubated at 37°C for 5 h. The samples were neutralized to pH 6, freeze-dried, reconstituted with water and assayed.…”

Section: Analyticalmentioning

confidence: 99%

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Insulin mediators in man: effects of glucose ingestion and insulin resistance

et al. 1997

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Insulin generates/releases chemical substances that alter the activities of purified enzymes [1,2] and the metabolism of intact cells [3,4] in an insulin mimetic fashion. These substances have therefore been termed mediators or second messengers of insulin [5]. Two different insulin mediators have been separated from rat liver [6]. These mediators have been identified as inositol phosphoglycans (IPGs), containing inositol, non-acetylated amino sugars, neutral sugars, ethanolamine, phosphate and, possibly, amino acids [5]. One contains d -chiro-inositol and activates pyruvate dehydrogenase (PDH) phosphatase, whereas another contains myo-inositol and inhibits cyclic AMP-dependent protein kinase (PKA). Injection of each of these IPGs into low-dose streptozotocin-diabetic rats lowers blood glucose [7].Body fluids of patients with non-insulin-dependent diabetes mellitus (NIDDM) have abnormally low levels of Summary Insulin mediators (inositol phosphoglycans) have been shown to mimic insulin action in vitro and in intact mammals, but it is not known which mediator is involved in insulin action under physiological conditions, nor is it known whether insulin resistance alters the mediator profile under such conditions. We therefore investigated the effects of glucose ingestion on changes in the bioactivity of serum inositol phosphoglycan-like substances (IPG) in healthy men and insulin resistant (obese, non-insulin-dependent diabetic) men. Two classes of mediators were partially purified from serum before and after glucose ingestion. The first was eluted from an anion exchange resin with HCl pH 2.0, and bioactivity was determined by activation of pyruvate dehydrogenase in vitro. The second was eluted with HCl pH 1.3, and bioactivity was determined by inhibition of cyclic AMP-dependent protein kinase. In healthy men, the bioactivity of the pH 1.3 IPG was not altered by glucose ingestion, whereas bioactivity of the pH 2.0 IPG increased to approximately 120 % of the pre-glucose ingestion value at 60-240 min post-glucose ingestion (p < 0.05 vs pre-glucose). There was no change in either IPG after glucose ingestion in the insulin-resistant group. These data suggest that the pH 2.0 IPG plays an important role in mediating insulin's effect on peripheral glucose utilization in man under physiological conditions. The data further show, for the first time, a defective change in the bioactivity of an insulin mediator isolated from insulin-resistant humans after hyperinsulinaemia, suggesting that inadequate generation/release of IPGs is associated with insulin resistance. [Diabetologia (1997) 40: 557-563] Keywords Inositol phosphoglycans, non-insulin dependent diabetes mellitus, pyruvate dehydrogenase, cyclic AMP dependent protein kinase.

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Section: Analyticalmentioning

confidence: 99%

“…These substances have therefore been termed mediators or second messengers of insulin [5]. Two different insulin mediators have been separated from rat liver [6]. These mediators have been identified as inositol phosphoglycans (IPGs), containing inositol, non-acetylated amino sugars, neutral sugars, ethanolamine, phosphate and, possibly, amino acids [5].…”

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confidence: 99%

Insulin mediators in man: effects of glucose ingestion and insulin resistance

et al. 1997

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“…We successfully separated and analyzed the two purified bioactive fractions from rat liver. The cAMP inhibitor contained myo-inositol and glucosamine (38), whereas the PDH phosphatase (PDHP) stimulator contained, to our surprise, DCI and galactosamine (39). Both the cAMP kinase inhibitor and the PDHP stimulator were insulinmimetic in vivo (40).…”

Section: Minnesota Years: a Bookmentioning

confidence: 99%

Inositol, Glycogen, Insulin, and Six Nobelists

Larner

2013

Journal of Biological Chemistry

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“…5 The other, so-called pH 2 mediator, stimulates pyruvate dehydrogenase phosphatase and contains chiro-inositol and galactosamine. 6 The lack of complete structural characterization has led to intense synthetic efforts by several groups [7][8][9][10][11] in the hope of determining the structural features necessary for mimicking insulin action. Herein, we report the syn- thesis of oligosaccharides 1-5.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of inositol glycan cyclic phosphates

Jaworek

Iacobucci

Calias

et al. 2001

Carbohydrate Research

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An efficient synthesis of tri-, tetra-, and pentasaccharide cyclic phosphates 1-5, structurally related to natural inositol phosphate glycans, is reported. The title compounds were assembled by PhSeOTf-promoted glycosylation of the known glucosamine precursor, t-butyldimethylsilyl 2-azido-3,6-di-O-benzyl-2-deoxy-b-D-glucopyranoside (8) with protected 1-methylthio mono-, di-, and trimannosides 7a-c, and, after conversion into glycosyl fluorides, Cp 2 ZrCl 2 -AgOTf-promoted glycosylation of differentially protected optically pure 1D-myo-inositol 11. The syntheses were completed by installing the cyclic phosphate moieties with methylpyridinium dichlorophosphate and finally, removal of all protecting groups by dissolving-metal reduction.

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Rat liver insulin mediator which stimulates pyruvate dehydrogenase phosphatase contains galactosamine and D-chiroinositol

Cited by 208 publications

References 18 publications

Insulin mediators in man: effects of glucose ingestion and insulin resistance

Insulin mediators in man: effects of glucose ingestion and insulin resistance

Inositol, Glycogen, Insulin, and Six Nobelists

Synthesis of inositol glycan cyclic phosphates

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