Further observations on hypoglycaemia in hepatocellular carcinoma

McFadzean, A. J. S.; Yeung, R. T. T.

doi:10.1016/0002-9343(69)90148-x

Cited by 96 publications

(46 citation statements)

References 29 publications

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“…A somewhat similar distinction between two types of hepatoma to that suggested by McFadzean & Yeung (1969) was drawn by Wu et al (1988) who noted that patients with hypoglycaemia tended to have higher plasma IGF-II and lower plasma IGF-I levels than those without it.…”

Section: Hepatomassupporting

confidence: 66%

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Tumours producing hypoglycaemia

Teale¹

1998

Endocrine Related Cancer

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Section: Hepatomassupporting

confidence: 66%

“…Many of the large series of NICTH due to primary hepatoma have emanated from the far east where hepatomas are common (McFadzean & Yeung 1956, 1969 but it is also disproportionately common in the USA (Wu et al 1988, Shapiro et al 1990 as well as in the UK.…”

Section: Hepatomasmentioning

confidence: 99%

Tumours producing hypoglycaemia

Teale¹

1998

Endocrine Related Cancer

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“…To maintain plasma glucose at normal levels in patients with tumor hypoglycemia, daily glucose requirements of as much as 1.6 kg have been reported (1). Since the normal rate of hepatic glucose output is -2-2.5 mg/kg per min (39,40), the hypoglycemia cannot result from reduced hepatic glucose output alone and glucose uptake must be increased to a substantial degree.…”

Section: Subjectsmentioning

confidence: 99%

“…McFadzean and Yeung separated the occurrence of hypoglycemia in Chinese patients with hepatocellular carcinoma into two distinct types (1). Patients with type A hypoglycemia developed mild reductions in plasma glucose which were readily treated, occurred during the terminal stages of the illness, and were associated with cachexia.…”

Section: Introductionmentioning

confidence: 99%

Tumor hypoglycemia: relationship to high molecular weight insulin-like growth factor-II.

Shapiro¹,

Bell²,

Polonsky³

et al. 1990

J. Clin. Invest.

119

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The mechanism of tumor-associated hypoglycemia was examined in 11 patients with hepatocellular carcinoma, 6 of whom presented with severe hypoglycemia and 5 in whom plasma glucose was persistently normal. Serum insulin levels in the hypoglycemic patients were low. Although total serum insulinlike growth factor II (IGF-II) levels in both groups of tumor patients were lower than normal, tumor tissue from hypoglycemic patients contained levels of IGF-II mRNA that were 10-20-fold higher than those present in normal liver.IGF-II immunoreactivity consisted in all cases of a mixture of both higher molecular weight forms and material having the character of IGF-II itself. The former comprised a greater proportion of total IGF-II, in patients with hypoglycemia. Studies to characterize the interactions of IGF-II with serum proteins showed that (a) the radiolabeled peptide bound to an -40,000-D protein in sera from both hypoglycemic patients and normal subjects, (b) sera from hypoglycemic patients and normal subjects had similar capacity to bind the radiolabeled peptide, and (c) the apparent affinities of serum binding proteins for IGF-II were the same for both hypoglycemic patients and normal subjects. Whereas, acid extracted, tumor-derived IGF-II immunoreactive peptides with low or intermediate molecular weights bound to serum proteins in a manner indistinguishable from that of IGF-II itself, the highest molecular weight IGF-II immunoreactive peptide exhibited negligible ability to compete for radiolabeled ligand binding to serum proteins. The low affinity of serum binding proteins for this component suggests that high molecular weight IGF-II immunoreactivity might circulate free and be available for interaction with cell-surface receptors. (J. Clin. Invest. 1990.

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“…The difference in ability to maintain blood glucose levels in animals bearing the MAC16 and MAC13 tumours appears to be unrelated either to food intake or the glucose consumption by the tumour cells, since glucose utilisation by the MAC13 tumour has been shown to be significantly higher than by the MAC16 tumour (Mulligan & Tisdale, 1991). McFadzean and Yeung (1969) were able to separate two types of hypoglycaemia in patients with hepatocellular carcinoma. Those with type A hypoglycaemia developed mild reductions in plasma glucose associated with cachexia, while those with type B hypoglycaemia demonstrated marked decreases in glucose levels in patients in whom cachexia was not a feature.…”

Section: Discussionmentioning

confidence: 93%

Tumour-associated hypoglycaemia in a murine cachexia model

Tisdale²

1992

Br J Cancer

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SummaryAnimals bearing a cachexia-inducing tumour, the MAC16 adenocarcinoma, showed a progressive decrease in blood glucose levels with increasing weight loss, while animals bearing a histologically similar tumour, the MAC13 adenocarcinoma, showed no change in either body weight or blood glucose levels with growth of the tumour. The effect of the MAC16 tumour on blood glucose levels appeared to be unrelated to food intake, glucose consumption by the tumour, or to the production of increased levels of IGF-I and IGF-II mRNA by the tumour cells. The relationship between the induction of cachexia and alteration in blood glucose levels remains unknown.A high rate of glucose consumption under both anaerobic and aerobic conditions is a characteristic feature of both experimental (Weber et al., 1961;Weber, 1977) and human tumours (Nolop et al., 1987). Alterations in glucose metabolism in tumour cells are associated with an increased intracellular concentration of glucose, which is tightly coupled with an over-expression of facilitative glucose transporter genes (Yamamoto et al., 1990), an increased transcription of the hexokinase gene (Johansson et al., 1985), as well as alterations in isoenzyme profiles of the enzymes involved in glycolysis (Weber et al., 1961). The enhanced glucose transport is not insulin-dependent, since hypoglycaemia often develops in both tumour-bearing animals (Bibby et al., 1987) and cancer patients (Heber et al., 1985) with normal or even decreased blood insulin levels. The architecture of solid tumours also plays an important role in determining the metabolic substrate for energy production. Large solid tumours tend to have a poor blood supply, and consequently become hypoxic, in which case glucose will become the predominant metabolic substrate, since the Embden-Meyerhof pathway is the only means of ATP production in the absence of oxygen.We have recently reported studies on glucose utilisation by tumour and host tissues in NMRI mice bearing the MAC16 colon adenocarcinoma, which is capable of inducing cachexia in recipient animals (Mulligan & Tisdale, 1991). Glucose consumption by the tumour was second only to brain and the increased demand for glucose was met by a decrease in glucose utilisation by host organs and in particular the brain. This study further investigates changes in blood glucose levels and the possible role of insulin-like growth factors (IGF) in the MAC16 model. Since antibodies to both mouse IGFI and IGFII were not readily available, we have chosen to measure their production in the MAC16 tumour indirectly, through the study of gene expression. Materials and methodsPure strain NMRI mice were bred in our own colony and were fed on a rat and mouse breeding diet (Pilsbury, Birmingham, UK) and water ad libitum. Fragments (1 x 2 mm) of either the MAC16 or MAC13 tumour were implanted into the flank of male NMRI mice (starting weight 28 g) by means of a trocar as described (Bibby et al., 1987

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Further observations on hypoglycaemia in hepatocellular carcinoma

Cited by 96 publications

References 29 publications

Tumours producing hypoglycaemia

Tumours producing hypoglycaemia

Tumor hypoglycemia: relationship to high molecular weight insulin-like growth factor-II.

Tumour-associated hypoglycaemia in a murine cachexia model

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