Alcohol-related diols cause acute insulin resistance in vivo

Xu, Dan; Dhillon, Amardeep S.; Abelmann, Anke; Croft, Kevin D.; Palmer, T.N.

doi:10.1016/s0026-0495(98)90320-1

Cited by 26 publications

(15 citation statements)

References 27 publications

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“…We used MAS-NMR of CR2-TAg prostate NE tumor cells in culture and discovered a prominent metabolite, propylene glycol (1, 2-propanediol), known to cause insulin resistance in rodents [137]. GeneChip-based metabolic reconstructions disclosed that these tumor cells could convert glycine to propylene glycol through an amine oxidase, predicted to be ABP1; propylene glycol could then be converted to pyruvate.…”

Section: Nmr Approaches To Ne Cancer Metabolismmentioning

confidence: 99%

Current concepts in neuroendocrine cancer metabolism

Ippolito

2006

Pituitary

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Neuroendocrine (NE) cancers occur in multiple anatomic locations and range in prognosis from indolent to aggressive. In addition, adenocarcinomas can express gene products associated with NE cells, referred to as NE differentiation (NED), which correlates with poor prognosis and aggressive disease. Several metabolites and peptides produced by NE cells have been discovered that engage in cellular signaling and have autocrine and paracrine effects on cancer cell proliferation. This review focuses on the current knowledge of small molecule metabolism in NE cancers involving the synthesis of biogenic amine, polyamine, and amino acid neurotransmitters. Systems biology-directed approaches to NE cancer metabolism using gene expression profiling, liquid chromatography/mass spectrometry (LC/MS) and nuclear magnetic resonance (NMR) are also discussed. Furthermore, knowledge of metabolic and signaling pathways in NE cancers has led to the successful implementation of therapeutic regimens in cell culture and animal models of NE carcinogenesis.

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Section: Nmr Approaches To Ne Cancer Metabolismmentioning

confidence: 99%

Current concepts in neuroendocrine cancer metabolism

Ippolito

2006

Pituitary

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“…Blood glucose levels in STZ-diabetic rats were kept as close as possible to levels typical of nondiabetic animals with a twice-daily injection of a slow-acting insulin (Humulin-NPH, Eli Lilly, West Ryde, NSW, Australia) for approximately 10 days before the start of the experiments (STZ-diabetic rats received~2 units of insulin in the morning and~4.5 units of insulin in the late afternoon, whereas control animals received a physiological saline). In the rats used for the 2-deoxy-[ 3 H]glucose utilization experiments, an indwelling catheter was inserted into the right jugular vein and exteriorized through the back of the neck as described previously [22]. On the day of the experiments, food was withdrawn at the start of the light cycle (06:00 hour), insulin was injected as per normal, and blood glucose levels were measured before the start of every experiment, and only the STZ-diabetic rats with blood glucose levels close to those of nondiabetic animals were used on that day.…”

Section: Animalsmentioning

confidence: 99%

“…The experimental approach adopted to evaluate average glucose utilization rates by individual muscles was on the basis of an established tracer technique described in more details in an earlier report from this and other laboratories [19,20,22,26]. Briefly, cannulated rats either at rest or immediately after high-intensity swimming were administered an intravenous bolus of 50 lCi 2-deoxy-[ 3 H]glucose (Amersham) in 0.9% NaCl and the line washed with saline.…”

Section: Glucose Utilization Ratesmentioning

confidence: 99%

“…Briefly, cannulated rats either at rest or immediately after high-intensity swimming were administered an intravenous bolus of 50 lCi 2-deoxy-[ 3 H]glucose (Amersham) in 0.9% NaCl and the line washed with saline. Several blood samples were then taken at time intervals [22] for the next 30 minutes. Immediately after the removal of the last blood sample, the rats were injected via the cannula with sodium pentobarbitone to induce rapid anesthesia, and their red, white, and mixed gastrocnemius muscles were removed, freeze clamped using aluminum tongs precooled in liquid nitrogen, and stored at À808C until analyzed.…”

Section: Glucose Utilization Ratesmentioning

confidence: 99%

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Effect of impaired glucose uptake on postexercise glycogen repletion in skeletal muscles of insulin-treated streptozotocin-diabetic fasted rats

Ferreira

Palmer

et al. 2005

Metabolism

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“…In rats, propylene glycol produces acute reductions in basal and insulin-stimulated lipogenesis as well as glucose oxidation in adipocytes, plus acute reductions in glucose uptake in skeletal muscle (15,16). We found that fasting BALB͞c nu͞nu (nude) mice containing PNEC tumor xenografts exhibited significantly higher levels of serum free fatty acids (FFAs) compared to ageand gender-matched, non-tumor-bearing nude mouse controls maintained on the same diet and housed in the same microisolators (2.16 Ϯ 0.22 mM vs. 1.32 Ϯ 0.09 mM; n ϭ 5 animals per group; P Ͻ 0.01).…”

Section: Resultsmentioning

confidence: 99%

Linkage between cellular communications, energy utilization, and proliferation in metastatic neuroendocrine cancers

Ippolito

Merritt

Bäckhed

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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To identify metabolic features that support the aggressive behavior of human neuroendocrine (NE) cancers, we examined metastatic prostate NE tumors and derived prostate NE cancer (PNEC) cell lines from a transgenic mouse model using a combination of magic angle spinning NMR spectroscopy, in silico predictions of biotransformations that observed metabolites may undergo, biochemical tests of these predictions, and electrophysiological͞cal-cium imaging studies. Malignant NE cells undergo excitation and increased proliferation when their GABA A, glutamate, and͞or glycine receptors are stimulated, use glutamate and GABA as substrates for NADH biosynthesis, and produce propylene glycol, a precursor of pyruvate derived from glycine that increases levels of circulating free fatty acids through extra-NE cell effects. Treatment of nude mice containing PNEC tumor xenografts with (i) amiloride, a diuretic that inhibits Abp1, an enzyme involved in NE cell GABA metabolism, (ii) carbidopa, an inhibitor of dopa decarboxylase which functions upstream of Abp1, plus (iii) flumazenil, a benzodiazepine antagonist that binds to GABA A receptors, leads to significant reductions in tumor growth. These findings may be generally applicable: GeneChip data sets from 471 human neoplasms revealed that components of GABA metabolic pathways, including ABP1, exhibit statistically significant increases in their expression in NE and non-NE cancers.metabolome-directed cancer therapy ͉ electrophysiology ͉ GABA signaling and shunt ͉ magic angle spinning-NMR ͉ metabolomics N euroendocrine (NE) cancers originate from either neuroectoderm or endoderm-derived epithelia and display a wide range of aggressiveness. On one end of the spectrum, neuroectodermal NE cancers originating from adrenal chromaffin cells (phenochromocytomas) are typically indolent with Յ10% undergoing metastatic spread (1). In contrast, small cell carcinoma, an endodermal NE tumor comprising up to 25% of lung cancers, is usually disseminated at the time of initial diagnosis (2). Adenocarcinomas originating in non-NE cell lineages in the lung, prostate, stomach, and colon, as well as other organs, can express NE cell-associated gene products. This ''neuroendocrine differentiation'' (NED) correlates with poor prognosis (3-8), although the underlying mechanisms remain obscure.To characterize the metabolic features of NE cancers and adenocarcinomas with NED that affect prognosis, we produced CR2-large T antigen (TAg) transgenic mice where transcriptional regulatory elements from the mouse cryptidin-2 gene (Defcr2) were used to direct expression of simian virus 40 TAg in a subset of prostate NE cells. Males from multiple pedigrees develop metastatic NE cell cancer with a very stereotyped pattern of progression. Transgene expression commences at 7 weeks of age. Within 1 week, foci of transformed NE cells appear that phenocopy human prostatic intraepithelial neoplasia, the postulated precursor of conventional adenocarcinoma of the prostate (9, 10). By 16 weeks of age, there is local invasio...

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Alcohol-related diols cause acute insulin resistance in vivo

Cited by 26 publications

References 27 publications

Current concepts in neuroendocrine cancer metabolism

Current concepts in neuroendocrine cancer metabolism

Effect of impaired glucose uptake on postexercise glycogen repletion in skeletal muscles of insulin-treated streptozotocin-diabetic fasted rats

Linkage between cellular communications, energy utilization, and proliferation in metastatic neuroendocrine cancers

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