Rabbit lens and retina phosphorylate glucose through a glucokinase-like enzyme: Study in normal and spontaneously hyperglycemic animals

Iannello, Silvia; Campione, Rosa; Volpicelli, Giovanni; Belfiore, Francesco

doi:10.1016/1056-8727(94)00080-8

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…The V max for hexokinase with glucose as substrate is much lower than in brain, possibly reflecting the decreased glucose utilisation in white matter compared with grey matter (Clarke and Sokoloff, 1999). It has been reported in rabbit optic nerve that the K m for phosphorylation of glucose by hexokinase is in the low millimolar range implying that glucokinase is present (Iannello et al, 1994(Iannello et al, , 1996, but we could not replicate these results. The V max of hexokinase in MON remains low with fructose as substrate but the K m increases reflecting decreased affinity.…”

Section: Fructose Metabolismcontrasting

confidence: 70%

Fructose Metabolism in the Adult Mouse Optic Nerve, A Central White Matter Tract

Fowler

Rathbone

Allen

et al. 2006

J Cereb Blood Flow Metab

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Our recent report that fructose supported the metabolism of some, but not all axons, in the adult mouse optic nerve prompted us to investigate in detail fructose metabolism in this tissue, a typical central white matter tract, as these data imply efficient fructose metabolism in the central nervous system (CNS). In artificial cerebrospinal fluid containing 10 mmol/L glucose or 20 mmol/L fructose, the stimulus-evoked compound action potential (CAP) recorded from the optic nerve consisted of three stable peaks. Replacing 10 mmol/L glucose with 10 mmol/L fructose, however, caused delayed loss of the 1st CAP peak (the 2nd and 3rd CAP peaks were unaffected). Glycogen-derived metabolic substrate(s) temporarily sustained the 1st CAP peak in 10 mmol/L fructose, as depletion of tissue glycogen by a prior period of aglycaemia or high-frequency CAP discharge rendered fructose incapable of supporting the 1st CAP peak. Enzyme assays showed the presence of both hexokinase and fructokinase (both of which can phosphorylate fructose) in the optic nerve. In contrast, only hexokinase was expressed in cerebral cortex. Hexokinase in optic nerve had low affinity and low capacity with fructose as substrate, whereas fructokinase displayed high affinity and high capacity for fructose. These findings suggest an explanation for the curious fact that the fast conducting axons comprising the 1st peak of the CAP are not supported in 10 mmol/L fructose medium; these axons probably do not express fructokinase, a requirement for efficient fructose metabolism.

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Section: Fructose Metabolismcontrasting

confidence: 70%

Fructose Metabolism in the Adult Mouse Optic Nerve, A Central White Matter Tract

Fowler

Rathbone

Allen

et al. 2006

J Cereb Blood Flow Metab

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“…Another important consideration with regards to the impact of GAM on the retina is that retinal tissue homogenates exhibit glucokinase activity (33). Unlike hexokinase, glucokinase is not negatively regulated by the production of G6P.…”

Section: Discussionmentioning

confidence: 99%

Glucosamine induces REDD1 to suppress insulin action in retinal Müller cells

Moore

Miller

Dennis

2016

Cellular Signalling

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Resistance to insulin action is a key cause of diabetic complications, yet much remains unknown about the molecular mechanisms that contribute to the defect. Glucose-induced insulin resistance in peripheral tissues such as the retina is mediated in part by the hexosamine biosynthetic pathway (HBP). Glucosamine (GAM), a leading dietary supplement marketed to relieve the discomfort of osteoarthritis, is metabolized by the HBP, and in doing so bypasses the rate-limiting enzyme of the pathway. Thus, exogenous GAM consumption potentially exacerbates the resistance to insulin action observed with diabetes-induced hyperglycemia. In the present study, we evaluated the effect of GAM on insulin action in retinal Müller cells in culture. Addition of GAM to Müller cell culture repressed insulin-induced activation of the Akt/mTORC1 signaling pathway. However, the effect was not recapitulated by chemical inhibition to promote protein O-GlcNAcylation, nor was blockade of O-GlcNAcylation sufficient to prevent the effects of GAM. Instead, GAM induced ER stress and subsequent expression of the protein Regulated in DNA Damage and Development (REDD1), which was necessary for GAM to repress insulin-stimulated phosphorylation of Akt on Thr308. Overall, the findings support a model whereby GAM promotes ER stress in retinal Müller cells, resulting in elevated REDD1 expression and thus resistance to insulin action.

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“…In contrast, increased glycolysis is mediated by suppression of product inhibition of hexokinase by G6P (42) (and, possibly, by increased phosphorylation of glucose by glucokinase [43]). Elevated levels of G6P and proportional increases in F6P (Table 2) support this conclusion.…”

Section: Different Mechanisms Mediate Increases In Nadhc and Glycolysmentioning

confidence: 99%

Interactions Between Hyperglycemia and Hypoxia

et al. 2004

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The primary aim of these experiments was to assess in vitro effects of hyperglycemia (30 mmol/l glucose) and hypoxia (PO 2 ‫؍‬ 36 torr) of 2-h duration, separately and in combination, on cytosolic and mitochondrial free NADH (NADHc and NADHm, respectively) in retinas from normal rats. NADH is the major carrier of electrons and protons that fuel ATP synthesis and several metabolic pathways linked to diabetic complications. T he importance of duration and severity of hyperglycemia in the development of diabetic retinopathy was clearly established by the Diabetes Control and Complications Trial (1); however, the mechanisms that mediate early and late retinal vascular dysfunction and structural changes remain unclear.Proliferative retinopathy is widely attributed to increased production of vascular endothelial growth factor evoked by hypoxia/ischemia caused by capillary closure and nonperfusion that develop relatively early after the onset of diabetes (2).The possibility that hyperglycemia and hypoxia may interact via a common metabolic imbalance(s) to initiate and/or exacerbate complications of diabetes is suggested by the correspondence of several redox, metabolic, and pathophysiological changes evoked by either condition alone. Examples include an increased ratio of reduced to oxidized free cytosolic NADc (3-16), increased production of free radicals (3,17-24) and vascular endothelial growth factor (17,19,(25)(26)(27)(28), accumulation of triose phosphates (7,9,10,13-15), activation of protein kinase C (PKC) (22,28 -30), decreased Na ϩ /K ϩ -ATPase activity (3,30 -33), early increases in blood flow (3,(33)(34)(35), and paradoxical protective effects of diabetes and brief periods of hypoxia/ ischemia (i.e., ischemic preconditioning) that attenuate dysfunction/injury evoked by subsequent more severe hypoxia/ischemia (3,29,36 -38).An increase in free NADH/NAD ϩ c appears to be the best candidate metabolic imbalance for mediating pathophysiological changes common to diabetes and hypoxia (3,38). This redox imbalance develops when electrons and protons are transferred to free oxidized NAD ϩ c (reducing it to NADHc) faster than electrons and protons carried by NADHc are used for ATP synthesis in mitochondria by oxidative phosphorylation. Hypoxia increases free NADHc because lack of O 2 impairs utilization of electrons and protons carried by mitochondrial NADHm for oxidative phosphorylation. The mass action effect of electrons and protons accumulating in NADHm restrains transfer of electrons and protons from free NADHc to NAD ϩ m by the malate-aspartate electron shuttle; thus, electrons and protons accumulate in, and elevate, free NADHc.In cells for which glucose uptake is insulin-independent, hyperglycemia augments glucose uptake and metabolism via the sorbitol pathway. In the second step of the pathway, sorbitol is oxidized to fructose by sorbitol dehydrogenase, which catalyzes transfer of a hydride ion (:H Ϫ ) from sorbitol to free NAD ϩ c (reducing it to NADHc) and removal of a second hydrogen atom that is released i...

show abstract

Rabbit lens and retina phosphorylate glucose through a glucokinase-like enzyme: Study in normal and spontaneously hyperglycemic animals

Cited by 6 publications

References 40 publications

Fructose Metabolism in the Adult Mouse Optic Nerve, A Central White Matter Tract

Fructose Metabolism in the Adult Mouse Optic Nerve, A Central White Matter Tract

Glucosamine induces REDD1 to suppress insulin action in retinal Müller cells

Interactions Between Hyperglycemia and Hypoxia

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