Membrane Lipid Alterations and Na+-Pumping Activity in Erythrocytes From IDDM and NIDDM Subjects

Baldini, P.; Incerpi, Sandra; Lambert-Gardini, S.; Spinedi, Angelo; Luly, Paolo

doi:10.2337/diab.38.7.825

Cited by 40 publications

(8 citation statements)

References 37 publications

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“…Erythrocyte properties are significantly modified by hyperglycaemia, including altered membrane lipid composition [72], impaired filterability [73], altered red cell deformability [74], and increased adhesion [75]. This is thought to arise from a decrease in the activity of red cell Na/K-ATPase [76] as well as modifications in protein structure due to oxidation [77] and the accumulation of AGEs on the red cell membrane [78].…”

Section: Red Cell Abnormalities In Diabetesmentioning

confidence: 99%

Anaemia in Diabetes: An Emerging Complication of Microvascular Disease

Thomas

Tsalamandris

MacIsaac

et al. 2005

CDR

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Diabetes as the dominant cause of ESRD is also the major cause of renal anaemia. However, most patients with diabetic kidney disease will succumb to co-morbid vascular disease or heart failure before developing severe renal impairment. In these patients, anaemia is also common finding, with a 2-3 times greater prevalence and earlier onset than in patients with renal impairment from other causes. We have recently shown that at least one in five outpatients with type 1 or type 2 diabetes in tertiary referral clinics have anaemia, in whom it constitutes a significant additional burden. Impaired renal erythropoietin release in response to declining haemoglobin levels appears to be the major contributor to anaemia in diabetes. This may be due to the predominance of damage to cells and vascular architecture of the renal tubulointerstitium associated with diabetic nephropathy that may be apparent, like albuminuria, before demonstrable changes in renal function. In addition, systemic inflammation, autonomic neuropathy and reduce red cell survival may also compound anaemia in diabetes. While anaemia may be considered a marker of diabetic kidney disease, reduced haemoglobin levels, even within the normal range, identify diabetic patients with an increased risk of hospitalisation and mortality. Anaemia may also be significant in determining the outcome of heart failure and hypoxia-induced organ damage in patients with diabetes. Upcoming studies will determine whether correction of anaemia in diabetes will lead to improved outcomes in these patients.

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Section: Red Cell Abnormalities In Diabetesmentioning

confidence: 99%

Anaemia in Diabetes: An Emerging Complication of Microvascular Disease

Thomas

Tsalamandris

MacIsaac

et al. 2005

CDR

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“…Patients with DM demonstrate significant hyperglycemiainduced metabolic and functional disorders of the RBC such as cell membrane lipid abnormalities [87], suppression of RBC filterability [88] and deformability [89] and alteration of RBC adhesion properties [90].…”

Section: Renal Blood Cells Disordersmentioning

confidence: 99%

Less known pathophysiological mechanisms of anemia in patients with diabetic nephropathy

Παππά¹,

Dounousi

Duni

et al. 2015

Int Urol Nephrol

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Diabetes mellitus (DM) is currently considered a modern global epidemic, and diabetic nephropathy (DN) is the most common cause of chronic kidney disease (CKD). Anemia is one of the most significant complications of CKD, and it is mainly attributed to insufficient erythropoietin (EPO) production. However, anemia develops earlier in the course of CKD among patients with DM, and the severity of anemia tends to be more marked in these patients compared to nondiabetic subjects, regardless of the stage of CKD. In this review, we focus on the "less known" complex interacting mechanisms which are involved in the pathophysiology of anemia associated with DN. Although the major cause of anemia in DN is considered to be an inappropriate response of the plasma EPO concentration to anemia, several other possible mechanisms have been suggested. Glomerular hyperfiltration, proteinuria, renal tubular dysfunction and interstitial fibrosis are among the main culprits. On the other hand, systemic effects such as chronic inflammation, autonomic neuropathy and the renin-angiotensin system are also involved. Finally, several medications are considered to aggravate anemia associated with DN. Since anemia is an important predictor of quality of life and is implicated in the increased burden of cardiovascular morbidity and mortality, further research is required to elucidate its pathogenesis in diabetic patients.

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“…This increased activity of erythrocyte Na-pump in diabetes mellitus might suggest an increase of cation permeability associated with a possible disorder in the diabetic membrane. Conversely, the Na pumping activity (estimated from both NKA and ouabain-binding) was observed by others to be significantly decreased in type-1 and type-2 diabetic patients and to retain the insulin sensitivity only in young type-1 diabetics [46]. A significant reduction of NKA activity in erythrocyte membranes of type-1 diabetic patients, compared with matched controls, with similar contents of erythrocyte Na + and K + ion was also reported; when erythrocyte membranes of diabetic patients were incubated with their own plasma (probably containing higher concentration of a specific activator of NKA enzyme), a significant increase was found in enzyme activity, this effect being not influenced by the metabolic control [47].…”

Section: Pathophysiological Relevance Of Nkamentioning

confidence: 99%

Na+, K+-ATPase: Ubiquitous Multifunctional Transmembrane Protein and its Relevance to Various Pathophysiological Conditions

Suhail

2010

J Clin Med Res

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The Na+, K+-ATPase (NKA) is an ubiquitous enzyme consisting of α, β and γ subunits, and is responsible for the creation and maintenance of the Na+ and K+ gradients across the cell membrane by transporting 3 Na+ out and 2 K+ into the cell. Sodium pump regulation is tissue as well as isoform specific. Intracellular messengers differentially regulate the activity of the individual NKA isozymes. Regulation of specific NKA isozymes gives cells the ability to precisely coordinate NKA activity to their physiological requirements. It is the only known receptor for the cardiac glycosides used to treat congestive heart failure and cardiac arrhythmias. Endogenous ligands structurally similar to cardiac glycosides may act as natural regulators of the sodium pump in heart and other tissues. Identification of naturally occurring regulators of NKA could initiate the discovery of new hormone-like control systems involved in the etiology of selected disease processes, hence the importance of understanding the relation of the sodium pump and its ligands to disease. Diabetes has a marked effect on the metabolism of a variety of tissues and because the NKA is critical for the membrane potential and many transports, a change in its activity in diabetes would have profound consequence in these tissues. NKA is also involved in hypertension, salt balance, cardiovascular and renal disorders, sperm capacitation, cell volume regulation, apoptosis, rheumatoid arthritis, sepsis, neurological disorders, lung edema clearance and preeclampsia. NKA activity and expression in the collecting duct of kidney are modulated physiologically by hormones like aldosterone, vasopressin, and insulin. NKA enzyme activity and subunit levels are reduced in carcinoma, NKA-β levels were highly reduced in an invasive form of human renal clear cell carcinoma, androgen-dependent prostate cancer, in early stages of urothelial cancer, as well as in poorly differentiated, highly motile carcinoma cell lines obtained from various tissues suggesting a functional link between reduced NKA-β expression and cancer progression. It could be a target for the development of anticancer drugs as it serves as a signal transducer, it is a player in cell adhesion and its aberrant expression and activity are implicated in the development and progression of different cancers.KeywordsNa+, K+-ATPase (NKA); Cardiotonic steroids (CTS); Diabetes; Hypertension; Cardiovascular and renal disorders; Signal transducer; Anticancer drugs

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Membrane Lipid Alterations and Na+-Pumping Activity in Erythrocytes From IDDM and NIDDM Subjects

Cited by 40 publications

References 37 publications

Anaemia in Diabetes: An Emerging Complication of Microvascular Disease

Anaemia in Diabetes: An Emerging Complication of Microvascular Disease

Less known pathophysiological mechanisms of anemia in patients with diabetic nephropathy

Na+, K+-ATPase: Ubiquitous Multifunctional Transmembrane Protein and its Relevance to Various Pathophysiological Conditions

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