Diabetic retinopathy is thought to result from chronic changes in the metabolic pathways of the retina. Hyperglycemia leads to increased intracellular glucose concentrations, alterations in glucose degradation and an increase in lactate/pyruvate ratio.
We measured lactate content in retina and other ocular and non-ocular tissues from normal and diabetic rats in the early stages of st…
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Evaluation of a sorbitol dehydrogenase inhibitor on diabetic peripheral nerve me…
AIMS/HYPOTHESIS: Studies of the role of sorbitol dehydrogenase in nerve functional deficits induced by diabetes reported contradictory results. We evaluated whether sorbitol dehydrogenase inhibition reduces metabolic abnormalities and enhances oxidative stress characteristic of experimental diabetic neuropathy.
METHODS: Control and streptozotocin-diabetic rats were treated with or wi… |
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Elevated glucose levels increase retinal glycolysis and sorbitol pathway metabol…
PURPOSE. To assess effects of elevated glucose levels on retinal glycolysis and sorbitol pathway metabolism.
METHODS. Freshly isolated retinas from normal male Sprague-Dawley rats were incubated for 2 hours at 37 degrees C, pH 7.45, in Krebs bicarbonate-Hepes buffer containing 5, 10, 20, or 30 mM glucose. Glycolytic metabolites, sorbitol, and fructose were measured in extracts of ret… |
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Effect of nicotinamide on the uptake and release of serotonin and GABA by cerebr…
Studies of neurotransmitter uptake and release by isolated rats brain cortex synaptosomes demonstrated that [2-14C]serotonin uptake was by 41% lower in streptozotocin-diabetic rats as compared to control. The [U-14C]GABA uptake was considerably elevated. [2-14C]serotonin and [U-14C]GABA release from the neurotransmitter pre-loaded synaptosomes showed significant elevation, especially during the fi…
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The use of nicotinamide in the prevention of type 1 diabetes.
Nicotinamide can protect the NOD mouse from diabetes if given early enough and in sufficient dose. The effect partly wanes with time. There is reduced islet inflammation. Similar protective effects can be demonstrated in quasi-experimental interventions in humans--both diabetes related and unrelated deemed at risk of developing diabetes by reason of having islet cell antibodies.
Nico… |
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Hyperglycemic Pseudohypoxia and Diabetic Complications.
In hypoxic tissues these vascular changes are linked to metabolic imbalances associated with impaired oxidation of NADH to NAD and the resulting increased ratio of NADH/NAD.
In hyperglycemic tissues these vascular changes also are linked to an increased ratio of NADH/NAD, in this case because of an increased rate of reduction of NAD to NADH. Several lines of evidence su… |
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Nicotinamide and Prevention of Insulin-dependent Diabetes Mellitus.
As a result of beta cell destruction, islet cell antibodies (ICA) can be demonstrated in the circulation. These antibodies can be detected up to eight years prior to overt IDDM.
Nicotinamide, a vitamin B3 derivative, interferes with the immune mediated beta-cell destruction by reducing the content of FR and NO and thereby reducing their deleterious effects. At the same … |
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Molecular Mechanisms of Beta-cell Destruction in Iddm: the Role of Nicotinamide.
Autoimmune processes are involved in pancreatic beta-cell destruction in type 1 diabetes... Generation of free radicals, DNA strand breaks, activation of the enzyme poly (ADP-ribose) polymerase (PARP), and depletion of intracellular nicotinamide adenine dinucleotide (NAD) appear to be common factors in beta-cell death, whether mediated by oxygen radicals, nitric oxide, or streptozotocin. |
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Pyridine nucleotides in glucose metabolism and diabetes: a review.
"Nicotinamide adenine dinucleotide (NAD) and its derivatives NADH, NADP and NADPH have regulatory functions in the generation of triose phosphates and pyruvate from glucose. In many studies of the influence of the diabetic state on relationships between pyridine nucleotide and glucose metabolism, the focus has been on the sorbitol pathway.
Less attention has been paid to other a… |
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Diabetic neuropathies. Metabolism of sorbitol in sciatic nerve tissue in strepto…
The increase of sorbitol and fructose levels caused by aldose reductase activation and sorbitol dehydrogenase inhibition were observed in sciatic nerve of streptozotocin-diabetic rats. Elevated polyol pathway activity has been implicated in the development of diabetic complications such as neuropathy.
The regulation of polyol pathway enzymes is based on the changes of redox state of … |
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Cerebrospinal fluid lactate in patients with diabetes mellitus and hypoglycaemic…
Cerebrospinal fluid (CSF) lactate and pyruvate concentrations were determined in 20 patients with diabetes mellitus but without disturbance of consciousness and five who recovered from hypoglycaemic coma.
CSF lactate was slightly but significantly higher in diabetes mellitus (1.78, SEM 0.04 m mol/l) than that in 15 control subjects (1.40, SEM 0.05 m mol/l). In those who recovered fro… |
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The burden of diabetic foot ulcers.
Lower extremity ulcers represent a major concern for patients with diabetes and for those who treat them, from both a quality of life and an economic standpoint. Studies to evaluate quality of life have shown that patients with foot ulcers have decreased physical, emotional, and social function. Analyses of economic impact have shown
(1) the majority of costs occur in the inpatient s… |
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The elevation of blood lactate is associated with a greater carbohydrate oxidati…
Increased blood lactate concentration and alterations of substrate utilization have been shown to be partly involved in development of insulin resistance in obese and type 2 diabetic patients.
As blood represents the first great distribution space and participates to lactate exchange in whole body, we investigated lactate transport in red blood cells at rest and the potential relatio… |
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