Glycolytic and gluconeogenic enzyme activities in renal cortex of diabetic rats

Anderson, J J; Stowring, Linda

doi:10.1152/ajplegacy.1973.224.4.930

Cited by 58 publications

(37 citation statements)

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“…Other examples of the unimpaired use of glucose in diabetes have been reported and in fact glucose over-utilization by these and some other tissues has been suggested from the elevated levels of hexokinase and the enzymes of the glycolytic and shunt pathways observed in kidney [33,34] and jejunum [33], from the elevated glycogen content and enzyme levels in placenta [35] and from the increased inositol formation in testis [29].…”

Section: Discussionmentioning

confidence: 99%

Effect of diabetes on the sugar nucleotides in several tissues of the rat

Spiro

1984

Diabetologia

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Summary. Studies have been carried out to determine the effect of diabetes on the concentrations of sugar nucleotides in several tissues of the rat. This represents one aspect of an investigation aimed at evaluating the role which alterations in the metabolism of glycoproteins or other glycoconjugates may play in the development of the long-term complications of this disease. Measurements were made of the nucleotides of hexoses, N-acetylhexosamines, hexuronic acids, and sialic acid in liver, kidney, skeletal muscle, testis and heart of alloxan-diabetic rats and age-matched controls. Of the intermediates studied, only UDP-glucose and UDP-galactose showed significant alterations in diabetes. The direction of the changes depended on the tissue, with the levels in liver and skeletal muscle being decreased, those in kidney and testis increased and the concentrations in heart being unchanged. In the diabetic liver, the concentrations of UDP-glucose was reduced to 0.75 that of normal, while in skeletal muscle both UDP-glucose and UDP-galactose were significantly decreased (diabetic to normal ratios of 0.67 and 0.64, respectively). Kidney and testis, on the other hand, showed elevations of both UDP-glucose and UDP-galactose, with the diabetic levels being 1.2 to 1.3 those of normal levels. The direction of change in UDPglucose in a tissue appeared to reflect its known ability to synthesize glycogen in diabetes. The finding of elevated UDPglucose and UDP-galactose concentrations in diabetic kidney is considered to be potentially of great importance to the increased synthesis of basement membrane collagen by this tissue.

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Section: Discussionmentioning

confidence: 99%

Effect of diabetes on the sugar nucleotides in several tissues of the rat

Spiro

1984

Diabetologia

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“…Cell numbers in these suspensions were estimated using an improved Neubauer hemocytometer (Hausser Scientific) and adjusted to ϳ10 7 cells/ml. Aliquots (2 ml) were then transferred to 25-ml Erlenmeyer flasks equipped with center wells designed specifically for CO 2 capture experiments (Kimble/Kontes, Vineland, NJ). All incubations were initiated by the direct addition of 1 Ci [1-14 C]Glc or [6][7][8][9][10][11][12][13][14] C]Glc (specific activity ϳ56.0 mCi/mmol) to the medium.…”

Section: Methodsmentioning

confidence: 99%

“…2 Thus, the inability of IGF-1 to mimic the effect of HB-EGF suggests that increased HK activity is not a general mitogenic effect in these cells. This inter-2 A. K. Singh and R. B. Robey, unpublished observations.…”

Section: Exogenous Hb-egf Increases Total Hk Activity In a Concentratmentioning

confidence: 96%

“…Three high affinity HK isoforms (HKI-III) are expressed in mammalian kidneys, but the specific intrarenal expression patterns, regulation, and relative importance of individual isoforms have not been fully addressed. Interestingly, the extant descriptions of altered HK activity in the adult kidney have been largely restricted to pathological conditions associated with renal functional and/or structural abnormalities (1)(2)(3)(4). Thus, as the principal renal cell type affected by a variety of pathologic conditions, including diabetic glomerulopathy and many forms of glomerulonephritis, the regulation of HK expression and activity in glomerular mesangial cells may have significant pathophysiologic, as well as physiologic, relevance.…”

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confidence: 99%

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Regulation of Mesangial Cell Hexokinase Activity and Expression by Heparin-binding Epidermal Growth Factor-like Growth Factor

Robey¹,

Ma²,

Santos³

et al. 2002

Journal of Biological Chemistry

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Heparin-binding epidermal growth factor -like growth factor (HB-EGF) expression and hexokinase (HK) activity are increased in various pathologic renal conditions. Although the mitogenic properties of HB-EGF have been well characterized, its effects on glucose (Glc) metabolism have not. We therefore examined the possibility that HB-EGF might regulate HK activity and expression in glomerular mesangial cells, which constitute the principal renal cell type affected by a variety of pathologic conditions. Protein kinase C (PKC)-dependent classic mitogenactivated protein kinase (MAPK) pathway activation has been associated with increased HK activity in this cell type, so we also examined dependence upon these signaling intermediates. HB-EGF (>10 nM) increased total HK activity over 50% within 12-24 h, an effect mimicked by other EGF receptor agonists, but not by IGF-1 or elevated Glc. EGF receptor and classic MAPK pathway antagonists prevented this increase, as did general inhibitors of gene transcription and protein synthesis. Both HB-EGF and phorbol esters activated the classic MAPK pathway, albeit via PKC-independent and PKC-dependent mechanisms, respectively. Both stimuli were associated with increased HK activity, selectively increased HKII isoform expression, and increased Glc metabolism via both the glycolytic-tricarboxylic acid cycle route and the pentose phosphate pathway. HB-EGF thus constitutes a novel regulator of mesangial cell HK activity and Glc metabolism. HKII is the principal regulated isoform in these cells, as it is in insulin-sensitive peripheral tissues, such as muscle. However, the uniform requirement for classic MAPK pathway activation distinguishes HKII regulation in mesangial cells from that observed in muscle. These findings suggest a novel mechanism whereby growth factors may couple metabolism to glomerular injury.

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“…Its enzymatic product, Glc 6-P, not only serves as a precursor for glycolysis, but also feeds into other important biological pathways leading to ATP generation, nucleic and fatty acid biosynthesis, and NADPH production. The discovery of high levels of HKII in the renal cortex in the present study may be particularly significant since altered HKII expression in the renal cortex has been associated with a variety of other pathological conditions including diabetes (Katzen et al, 1970;Anderson and Stowring, 1973;Steer et al, 1982).…”

Section: Introductionmentioning

confidence: 64%

Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic

Pysher

Sollome

Regan

et al. 2007

Toxicology and Applied Pharmacology

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Epidemiological studies link arsenic exposure to increased risks of cancers of the skin, kidney, lung, bladder and liver. Additionally, a variety of non-cancerous conditions such as diabetes mellitus, hypertension, and cardiovascular disease have been associated with chronic ingestion of low levels of arsenic. However, the biological and molecular mechanisms by which arsenic exerts its effects remain elusive. Here we report increased renal hexokinase II (HKII) expression in response to arsenic exposure both in vivo and in vitro. In our model, HKII was up-regulated in the renal glomeruli of mice exposed to low levels of arsenic (10 ppb or 50 ppb) via their drinking water for up to 21 days. Additionally, a similar effect was observed in cultured renal mesangial cells exposed to arsenic. This correlation between our in vivo and in vitro data provides further evidence for a direct link between altered renal HKII expression and arsenic exposure. Thus, our data suggest that alterations in renal HKII expression may be involved in arsenic-induced pathological conditions involving the kidney. More importantly, these results were obtained using environmentally relevant arsenic concentrations.

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Glycolytic and gluconeogenic enzyme activities in renal cortex of diabetic rats

Cited by 58 publications

References 0 publications

Effect of diabetes on the sugar nucleotides in several tissues of the rat

Effect of diabetes on the sugar nucleotides in several tissues of the rat

Regulation of Mesangial Cell Hexokinase Activity and Expression by Heparin-binding Epidermal Growth Factor-like Growth Factor

Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic

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