Peripheral nerve concentrations of glucose, fructose, sorbitol and myoinositol in diabetic and non-diabetic patients

Hale, P J; Nattrass, M.; Silverman, Stanley; Sennit, C.; Perkins, C. M.; Udén, Alf; Sundkvist, Göran

doi:10.1007/bf00279613

Cited by 51 publications

(21 citation statements)

References 17 publications

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“…As in diabetic patients the glucose concentration in peripheral nerves has been shown to be higher than that in the control subjects [30,31], the increase in glucose concentration may occur in The equilibrium dissociation affinity constant, K D , and the maximal specific binding, B max , were calculated by Scatchard analysis.…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

et al. 2002

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Cardiac scintigraphic studies with iodine-123 labeled metaiodobenzylguanidine ([(123)I]MIBG) have demonstrated global and regionally pronounced decreases in myocardial accumulation of radioactivity in diabetes. The aim of this study was to investigate the cause of the regional differential decrease in accumulation. To this end, we investigated the global and regional myocardial distribution of [(125)I]MIBG in GK/Crj (GK) rats [a model of non-insulin-dependent diabetes mellitus (NIDDM)] and assessed the responsibility of regional myocardial blood flow, myocardial and plasma norepinephrine (NE) content, and norepinephrine transporter (NET) function for the regional variations in [(125)I]MIBG accumulation. To investigate the responsibility of myocardial blood flow for the alterations in MIBG accumulation, dual-isotope autoradiographic studies with [(125)I]MIBG and technetium-99m hexakis-2-methoxy-2-isobutylisonitrile (MIBI), a tracer for the measurement of myocardial blood flow, were carried out in GK rats and control rats. The results in respect of the uptake of radioactivity into various myocardial regions were expressed as distribution absorption ratios [DAR = (radioactivity of tissue/g of tissue) x (body weight/total injected dose)]. In control rats, uptake of [(125)I]MIBG was significantly higher in the inferior wall than in the anterior wall (anterior wall, 6.35 +/- 0.90; inferior wall, 8.12 +/- 1.27: P < 0.001). On the other hand, in GK rats, uptake of [(125)I]MIBG was similar between the anterior wall and the inferior wall (anterior wall, 4.91 +/- 0.71; inferior wall, 4.81 +/- 0.69). Compared with control rats, uptake of [(125)I]MIBG in GK rats was decreased in both the anterior wall and the inferior wall. Uptake of (99m)Tc-MIBI was not significantly different between the anterior and inferior walls in control (anterior wall, 17.9 +/- 4.42; inferior wall, 18.1 +/- 4.52) and GK rats (anterior wall, 16.6 +/-8.03; inferior wall, 16.7 +/- 7.90), indicating that myocardial blood flow did not change regionally in either control or GK rats, and that the blood flow was not responsible for the differential decrease in MIBG accumulation in GK rats. Cardiac and plasma NE levels were measured using an HPLC-electrochemical detection system. The cardiac and plasma NE concentrations were not significantly different between control (anterior wall, 347 +/- 56 ng/g; inferior wall, 354 +/- 31 ng/g; plasma 9.38 +/- 2.10 ng/ml) and GK rats (anterior wall, 323 +/- 62 ng/g; inferior wall, 344 +/- 35 ng/g; plasma, 9.41 +/- 2.39 ng/ml). The density and affinity of NET were investigated by studying the binding of [(3)H]desipramine to cardiac membranes. The B(max) (fmol/mg protein) in the inferior wall was significantly higher than that in the anterior wall in the control rats (anterior wall, 364 +/- 28; inferior wall, 459 +/- 36: P < 0.05). On the other hand, there was no significant difference in the B(max) value between the anterior and inferior walls in GK rats (anterior wall, 263 +/- 42; inferior wall, 251 +/- 27). In conclusion,...

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Section: Discussionmentioning

confidence: 99%

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

et al. 2002

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“…The original suggestion is that the polyol pathway-associated sorbitol accumulation could cause osmotic damage to nerves, but there is no definite histological evidence of this, either from animal or human diabetic nerves [216]. Although sorbitol and fructose accumulations in diabetic nerves are accompanied by a decrease in the concentration of another myoinositol, reductions in nerve myoinositol concentrations in human diabetes have not been convincingly demonstrated [217,218]. Recent reports from several clinical trials of AR inhibitors seem to be disappointing.…”

Section: Involvement Of the Polyol Pathway In Diabetic Neuropathymentioning

confidence: 98%

Diabetic Vascular Complications: Pathophysiology, Biochemical Basis and Potential Therapeutic Strategy

Yamagishi¹,

Imaizumi

2005

CPD

410

387

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Diabetic vascular complication is a leading cause of end-stage renal failure, acquired blindness, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Recent large prospective clinical studies have shown that intensive glucose control reduces effectively microvascular complications among patients with diabetes, and insulin resistance and postprandial hyperglycemia seem to be involved in diabetic macrovascular complications. Chronic hyperglycemia is a major initiator of diabetic vascular complications. Indeed, high glucose, via various mechanisms such as increased production of advanced glycation end products, activation of protein kinase C, stimulation of the polyol pathway and enhanced reactive oxygen species generation, regulates vascular inflammation, altered gene expression of growth factors and cytokines, and platelet and macrophage activation, thus playing a central role in the development and progression of diabetic vascular complications. This article summarizes the molecular mechanisms of diabetic vascular complications and the potential therapeutic interventions that may prevent these disorders even in the presence of hyperglycemia, control of which is often difficult with current therapeutic options.

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“…As a result of low insulin and C-peptide [49], patients with diabetes have elevated blood glucose, which may lead to nerve damage [50]. The nerve damage is a result of alterations in the neural ion transport.…”

Section: Hyperglycaemiamentioning

confidence: 99%

Pathophysiology and Treatment of Diabetic Peripheral Neuropathy: The Case for Diabetic Neurovascular Function as an Essential Component

Kles

Vinik²

2006

CDR

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Worldwide, diabetes and its complications are major causes of morbidity, decreased quality of life, mortality and increasing health care costs. Patients with diabetes attempt to control blood pressure, lipids and blood glucose levels to decrease their risk of macrovascular and microvascular complications, such as diabetic peripheral neuropathy (DPN). Even with control of these risk factors for vascular disease, many patients still develop complications. Targeted therapies to the underlying mechanisms of diabetic neuropathy are essential to slow the progression of the disease. This review describes the signs, symptoms and diagnosis of DPN. Additionally, new therapies and the complex etiology that contributes to the development of diabetic neuropathy are described (oxidative stress, hyperglycemia, advanced glycated end products, autoimmunity, neurotrophic factors and protein kinase C beta).

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Peripheral nerve concentrations of glucose, fructose, sorbitol and myoinositol in diabetic and non-diabetic patients

Cited by 51 publications

References 17 publications

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

Diabetic Vascular Complications: Pathophysiology, Biochemical Basis and Potential Therapeutic Strategy

Pathophysiology and Treatment of Diabetic Peripheral Neuropathy: The Case for Diabetic Neurovascular Function as an Essential Component

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