Acidemia and Insulin Resistance in the Diabetic Ketoacidotic Rat

Cuthbert, C.; Alberti, K. G. M. M.

doi:10.1016/s0026-0495(78)80008-0

Cited by 50 publications

(26 citation statements)

References 18 publications

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“…This finding indicates that acidosis does not contribute to loss of IIS in the daw mutants, as has been proposed by a few vertebrate studies where metabolic acidosis seems to lead to insulin resistance (30,31). It is important to note that acidosis always correlates with the relative amount of metabolic acids.…”

Section: Discussionsupporting

confidence: 76%

Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster

Ghosh

O’Connor

2014

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

111

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The ability to maintain cellular and physiological metabolic homeostasis is key for the survival of multicellular organisms in changing environmental conditions. However, our understanding of extracellular signaling pathways that modulate metabolic processes remains limited. In this study we show that the Activin-like ligand Dawdle (Daw) is a major regulator of systemic metabolic homeostasis and cellular metabolism in Drosophila. We find that loss of canonical Smad signaling downstream of Daw leads to defects in sugar and systemic pH homeostasis. Although Daw regulates sugar homeostasis by positively influencing insulin release, we find that the effect of Daw on pH balance is independent of its role in insulin signaling and is caused by accumulation of organic acids that are primarily tricarboxylic acid (TCA) cycle intermediates. RNA sequencing reveals that a number of TCA cycle enzymes and nuclear-encoded mitochondrial genes including genes involved in oxidative phosphorylation and β-oxidation are up-regulated in the daw mutants, indicating either a direct or indirect role of Daw in regulating these genes. These findings establish Activin signaling as a major metabolic regulator and uncover a functional link between TGF-β signaling, insulin signaling, and metabolism in Drosophila.dIlp2 | hormone | acidosis

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Section: Discussionsupporting

confidence: 76%

Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster

Ghosh

O’Connor

2014

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

111

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“…Only a small increase in [H ϩ ] in tissues might significantly alter the affinity of a ligand to its receptor and the function of ion channels, transporters, enzymes, and structural proteins (2,7,17). Tissue acidosis may thus cause confounding biological effects.…”

Section: Discussionmentioning

confidence: 99%

“…Anesthesia was induced by a spontaneously inhalation of isoflurane, and the depth of the anesthesia was tested by probing the pedal withdrawal reflex, as recommended by Flecknell (5). The gas flow through the cylindrical mask (2 cm long with an inner diameter of 1.2 cm) was about 200 ml/min, which minimized animals' rebreathing of exhaled CO 2 …”

Section: Surgical Proceduresmentioning

confidence: 99%

Isoflurane-induced acidosis depresses basal and PGE₂-stimulated duodenal bicarbonate secretion in mice

Sjöblom

Nylander²

2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Sjöblom M, Nylander O. Isoflurane-induced acidosis depresses basal and PGE 2-stimulated duodenal bicarbonate secretion in mice. Am J Physiol Gastrointest Liver Physiol 292: G899 -G904, 2007. First published December 7, 2006; doi:10.1152/ajpgi.00398.2006.-When running in vivo experiments, it is imperative to keep arterial blood pressure and acid-base parameters within the normal physiological range. The aim of this investigation was to explore the consequences of anesthesia-induced acidosis on basal and PGE 2-stimulated duodenal bicarbonate secretion. Mice (strain C57bl/6J) were kept anesthetized by a spontaneous inhalation of isoflurane. Mean arterial blood pressure (MAP), arterial acid-base balance, and duodenal mucosal bicarbonate secretion (DMBS) were studied. Two intra-arterial fluid support strategies were used: a standard Ringer solution and an isotonic Na 2CO3 solution. Duodenal single perfusion was used, and DMBS was assessed by back titration of the effluent. PGE 2 was used to stimulate DMBS. In Ringer solution-infused mice, isofluraneinduced acidosis became worse with time. The blood pH was 7.15-7.21 and the base excess was about Ϫ8 mM at the end of experiments. The continuous infusion of Na 2CO3 solution completely compensated for the acidosis. The blood pH was 7.36 -7.37 and base excess was about 1 mM at the end of the experiment. Basal and PGE 2-stimulated DMBS were markedly greater in animals treated with Na 2CO3 solution than in those treated with Ringer solution. MAP was slightly higher after Na 2CO3 solution infusion than after Ringer solution infusion. We concluded that isoflurane-induced acidosis markedly depresses basal and PGE 2-stimulated DMBS as well as the responsiveness to PGE2, effects prevented by a continuous infusion of Na2CO3. When performing in vivo experiments in isoflurane-anesthetized mice, it is recommended to supplement with a Na2CO3 infusion to maintain a normal acid-base balance.anesthesia; murine physiology; in vivo; duodenal mucosal protection

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“…insulin resistance ; acidosis ; insulin receptor ; glucose uptake ; adipocyte It is well known that insulin resistance exists in diabetic patients during episodes of ketoacidosis (Walker et al 1963;Roth et al 1975;Ginsberg, H.N. 1977;Cuthbert and Alberti 1978;Whittaker et al 1981Whittaker et al , 1982Barrett et al 1982). Insulin resistance in metabolic ketoacidosis may be caused by several counterregulatory factors, of which low PH and ketone bodies are considered to be important factors (Ginsberg, H.N.…”

mentioning

confidence: 99%

Effect of Acidosis on Insulin Binding and Glucose Uptake in Isolated Rat Adipocytes.

Inamori

Yamatani

Fukase

et al. 1993

Tohoku J. Exp. Med.

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A., TOMINAGA, M. and SASAKI, H. Effect of Acidosis on Insulin Binding and Glucose Uptake in Isolated Rat Adipocytes. Tohoku J. Exp. Med., 1993, 169 (3), 205-213 To assess the mechanism of insulin resistance in metabolic acidosis, we investigated insulin receptor binding and glucose uptake in isolated rat epididymal adipocytes at three pHs, acidic (pH 6.8), neutral (pH 7.4) and alkaline (pH 8.0) groups. After male Sprague-Dawley rats weighing 220-240 g were submitted under chloral hydrate anesthesia, epididymal fat pads were dissected and isolated. [12511-insulin binding rate was not different between alkaline and neutral groups, but that of acidic group was markedly decreased to approximately 30% of neutral group at maximum specific insulin binding rate. Scatchard analysis showed that numbers of insulin receptors were not different among three groups, but values of binding affinity in acidic group was significantly lower than those of the others. 2-[3H]deoxy-D-glucose uptake of alkaline and neutral groups were increased to reach steady state immediately, but that of acidic group increased slowly and reached at maximum which was lower than the other two groups. Furthermore, 2-deoxy-D-glucose uptake against amount of bound insulin was lower in acidic group than other two groups. From these results, it is suggested that insulin resistance in metabolic acidosis resulted from the combined defects in binding affinity and post-binding process in the insulin receptor. insulin resistance ; acidosis ; insulin receptor ; glucose uptake ; adipocyte

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Acidemia and Insulin Resistance in the Diabetic Ketoacidotic Rat

Cited by 50 publications

References 18 publications

Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster

Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster

Isoflurane-induced acidosis depresses basal and PGE₂-stimulated duodenal bicarbonate secretion in mice

Effect of Acidosis on Insulin Binding and Glucose Uptake in Isolated Rat Adipocytes.

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Acidemia and Insulin Resistance in the Diabetic Ketoacidotic Rat

Cited by 50 publications

References 18 publications

Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster

Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster

Isoflurane-induced acidosis depresses basal and PGE2-stimulated duodenal bicarbonate secretion in mice

Effect of Acidosis on Insulin Binding and Glucose Uptake in Isolated Rat Adipocytes.

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Isoflurane-induced acidosis depresses basal and PGE₂-stimulated duodenal bicarbonate secretion in mice