Cell membrane dynamics and insulin resistance in non-insulin-dependent diabetes mellitus

Tong, Peter C.Y.; Berrish, T. S.; Humphriss, D; Barriocanal, L.A.; Stewart, M. W.; Walker, Mark; Alberti, K. G. M. M.; Thomas, T.H.; Wilkinson, Robert W.

doi:10.1016/s0140-6736(95)90343-7

Cited by 47 publications

(29 citation statements)

References 6 publications

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“…The reduced availability of oxygen could thus contribute to both reducing the aerobic metabolism of glucose and fatty acid and consequently reducing the "thermogenesis" in muscle, brown adipose tissue, etc., and increasing the hypoxic state both in heart and endothelial cells (thus contributing to increasing the incidence of all of the cardiovascular pathologies that are often associated with obesity). Finally, this decrease in membrane fluidity promoted by the higher pro-oxidant status in erythrocytes could be the expression of a more generalized phenomenon involving other tissues as well, in particular, muscle tissue: a significant direct correlation between membrane fluidity and insulin resistance has already been observed both in noninsulin-dependent diabetes mellitus (24) and in obese patients (21). In the light of current experimental data, it could be of interest to investigate whether or not a suitable dietary integration of -3 fatty acids and antioxidants could promote significant beneficial effects for the improvement of the fluidity of erythrocyte membranes in particular and all other tissues in general, and if this improvement could be of some utility in the prevention of both obesity and all of the other cardiovascular diseases correlated with it.…”

Section: Discussionmentioning

confidence: 97%

Decreased membrane fluidity and altered susceptibility to peroxidation and lipid composition in overweight and obese female erythrocytes

Cazzola

Rondanelli

Russo-Volpe

et al. 2004

Journal of Lipid Research

149

111

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The increased generation of reactive oxygen species that occurs in the condition of obesity may be responsible for oxidative injury to erythrocyte membranes, which could lead to a decrease in tissue oxygenation. Therefore, we have looked into the effects of obesity on both indexes of oxidative damage and physical-chemical properties of erythrocyte membranes in 50 overweight or obese [25 Ͻ body mass index (BMI) Ͻ 33], normotensive, nondiabetic women and 50 age-matched lean healthy women (BMI Ͻ 25). In the obese group compared with the lean group, we found that a ) the onset of free radical-induced erythrocyte hemolysis and the ratio between reduced and oxidized glutathione were reduced, whereas the rate of free radicalinduced damage increased; b ) the n-3 fatty acid and the phospholipid contents decreased; c ) the ratio between cholesterol and phospholipids increased; and d ) the membrane fluidity decreased. These findings suggest an impairment of erythrocyte membrane physical-chemical properties in overweight and obese people as a consequence of oxidative injury that might be part of a pathogenetic mechanism responsible for obesity-related pathologies such as atherosclerosis and hypertension. -Cazzola, R., M. Rondanelli, S. Russo-Volpe, E. Ferrari, and B. Cestaro. Physiological oxidative metabolism and neutrophil activation occurring in the blood give rise to oxygen-reactive substances and other very active radical species that can irreversibly damage the surrounding macromolecules. In particular, these radicals can attack both the amino and thiol groups of proteins and the double bonds of polyunsaturated fatty acids in lipoproteins. Statistically significant correlations have been found between lipoprotein susceptibility to peroxidation, the degree of obesity, and the risk of developing cardiovascular disease (1). Because any increase in the rate of lipoprotein peroxidation not only diminishes their levels of polyunsaturated fatty acids but also consumes and reduces their antioxidant contents (vitamin E, ␤ -carotene, coenzyme Q, etc.), the consequence of these biochemical events in overweight and obese people is also a probable reduction of the "exchange rate" of both polyunsaturated fatty acids and lipophilic antioxidants that are normally transferred in the blood from the donor lipoproteins to the erythrocyte acceptor membranes. A decrease in both the degree of polyunsaturation of lipids and the antioxidant levels of the erythrocyte membrane could thus be expected, together with a decrease of both membrane fluidity and the activity of its membrane-bound enzymes. Because the erythrocyte membrane serves as a variable barrier to oxygen transport, the changes in its composition can induce cellular hypoxia in the tissue bed. Furthermore, because the size, shape, and diffusion capacity of a red blood cell depend on the structure of its membrane, alterations in membrane structure could lead to a decrease in tissue oxygenation (2). Such modifications of oxygen available in cardiovascular cells might be part ...

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Section: Discussionmentioning

confidence: 97%

Decreased membrane fluidity and altered susceptibility to peroxidation and lipid composition in overweight and obese female erythrocytes

Cazzola

Rondanelli

Russo-Volpe

et al. 2004

Journal of Lipid Research

149

111

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“…For example both insulin resistance [5] and Na-Li CT activity [9±11] are abnormal in subjects with diabetic nephropathy. Insulin resistance may be related to cell membrane fluidity (fluorescence anisotropy) [22] and Na-Li CT abnormalities are due to an NEM sensitive thiol group containing protein within the cell cytoskeleton-cell membrane complex [20,21].…”

Section: Discussionmentioning

confidence: 99%

Abnormal regulation of cell membrane fluidity in diabetic nephropathy

1998

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Diabetic nephropathy is a condition that appears to arise from an interaction between poor glycaemic control [1] and inherited factors [2]. Insulin-dependent diabetic (IDDM) patients with nephropathy are characteristically hypertensive, have diabetic retinopathy, are relatively insulin resistant and have raised levels of serum triglycerides [3±6]. In addition, rates of activity of cell membrane cation transporters, such as the sodium-hydrogen exchanger [7,8] and the sodium-lithium countertransporter (Na-Li CT) [9±11] are increased in patients with diabetic kidney disease. The very close association of these abnormalities suggests a common aetiology. Na-Li CT has a large inherited component [12] and, although it appears to have no pathophysiological role, may be an inherited marker for an abnormality Diabetologia (1998) Summary An abnormality of the physical properties of the cell membrane may underlie the defect that unites the clinical and biochemical abnormalities found in subjects with diabetic nephropathy. The cell membrane is linked both structurally and functionally with the cytoskeleton. The fluorescence anisotropy, a measure of membrane fluidity, was studied at baseline and after modulation of cytoskeletal proteins by thiol group alkylation with N-ethylmaleimide (NEM). 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess anisotropy in the deep hydrophobic regions of the lipid bilayer and trimethylammoniumdiphenylhexatriene (TMA-DPH) was used to assess the superficial, relatively hydrophilic regions. We compared 17 subjects with insulin-dependent diabetes mellitus (IDDM) and nephropathy with 17 control subjects with IDDM and 24 non-diabetic control subjects. Median TMA-DPH anisotropy (0.271 (0.239±0.332) vs 0.269 (0.258±0.281) vs 0.275 (0.246± 0.287)) and DPH anisotropy (0.221 (0.193±0.261) vs 0.227 (0.197±0.253) vs 0.226 (0.193±0.245)) were similar in erythrocytes from the three groups. However after alkylation of protein thiol groups with NEM clear differences emerged. In the control subjects with and without IDDM there was a significant fall in TMA-DPH anisotropy compared to the subjects with diabetic nephropathy in whom the addition of NEM had no effect (DTMA-DPH anisotropy ±0.005 (±0.020± + 0.006) vs ±0.005 (±0.011± + 0.016) vs + 0.002 (±0.010 ± + 0.008) p < 0.001). This finding was confirmed when the deep regions of the lipid bilayer were assessed using DPH (DDPH anisotropy ±0.017 (±0.029 ± ± 0.007.) vs ±0.015 (±0.029 ± + 0.001) vs + 0.003 (±0.021 ± + 0.018) p < 0.001). We conclude that cytoskeletal modulation of the physical properties of the cell membrane lipids by proteins is abnormal in subjects with diabetic nephropathy. Such an abnormality could explain some of the clinical and metabolic abnormalities found in this condition. [Diabetologia (1998) 41: 337±342]

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“…In type II diabetes, increased production of free fatty acids is considered to be a key factor [19]. Insulin resistance in humans correlates with cell membrane 'fluidity' [197], and insulin receptor function is regulated by the physical properties of the host lipid bilayer [198]. Nevertheless, in both cardiovascular diseases and type II diabetes the role of changes in bilayer physics is unknown, partly because of the complex changes in cell membrane lipid composition.…”

Section: Physiological Importance Of Lipid Bilayer Elasticitymentioning

confidence: 99%

Regulation of membrane protein function by lipid bilayer elasticity—a single molecule technology to measure the bilayer properties experienced by an embedded protein

Lundbæk

2006

J. Phys.: Condens. Matter

116

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Link back to DTU OrbitCitation (APA): Lundbaek, J. A. (2008). Regulation of membrane protein function by lipid bilayer elasticity-a single molecule technology to measure the bilayer properties experienced by an embedded protein. Abstract Membrane protein function is generally regulated by the molecular composition of the host lipid bilayer. The underlying mechanisms have long remained enigmatic. Some cases involve specific molecular interactions, but very often lipids and other amphiphiles, which are adsorbed to lipid bilayers, regulate a number of structurally unrelated proteins in an apparently non-specific manner. It is well known that changes in the physical properties of a lipid bilayer (e.g., thickness or monolayer spontaneous curvature) can affect the function of an embedded protein. However, the role of such changes, in the general regulation of membrane protein function, is unclear. This is to a large extent due to lack of a generally accepted framework in which to understand the many observations. The present review summarizes studies which have demonstrated that the hydrophobic interactions between a membrane protein and the host lipid bilayer provide an energetic coupling, whereby protein function can be regulated by the bilayer elasticity. The feasibility of this 'hydrophobic coupling mechanism' has been demonstrated using the gramicidin channel, a model membrane protein, in planar lipid bilayers. Using voltage-dependent sodium channels, N-type calcium channels and GABA A receptors, it has been shown that membrane protein function in living cells can be regulated by amphiphile induced changes in bilayer elasticity. Using the gramicidin channel as a molecular force transducer, a nanotechnology to measure the elastic properties experienced by an embedded protein has been developed. A theoretical and technological framework, to study the regulation of membrane protein function by lipid bilayer elasticity, has been established.

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Cell membrane dynamics and insulin resistance in non-insulin-dependent diabetes mellitus

Cited by 47 publications

References 6 publications

Decreased membrane fluidity and altered susceptibility to peroxidation and lipid composition in overweight and obese female erythrocytes

Decreased membrane fluidity and altered susceptibility to peroxidation and lipid composition in overweight and obese female erythrocytes

Abnormal regulation of cell membrane fluidity in diabetic nephropathy

Regulation of membrane protein function by lipid bilayer elasticity—a single molecule technology to measure the bilayer properties experienced by an embedded protein

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