Enhanced Na–Li countertransport: a marker of inherited susceptibility to type 2 diabetes

Vaccaro, Olga; Cuomo, Vittoria; Trevisan, Maurizio; Cirillo, Massimo; Panarelli, Walter; Laurenzi, Martino; Mancini, Mario; Riccardi, Gabriele

doi:10.1093/ije/dyi160

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…28 Nonetheless, it is intriguing to interpret our findings in the light of prospective data which show that enhanced Na + /Li + CT activity is a significant predictor for the development of diabetes in adults; this suggests that it could be viewed as a preclinical, possibly genetic, marker of inherited susceptibility to type 2 diabetes. 8 These implications need to be further tested. On the other hand, abnormalities in cellular ion-transport systems, including Na + /Li + CT, have been associated with increased intracellular concentrations of sodium and calcium and subsequently with a high proliferation rate and growth of vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

“…1 Abnormalities in the transmembrane transport system of sodium have been proposed as a factor that might be the phenotypic expression of coaggregation of hypertension and lipid abnormalities. 3 Elevated red cell sodium-lithium countertransport (Na + /Li + CT) activity has been demonstrated in patients with essential hypertension, [4][5][6] insulin resistance and diabetes mellitus, 7,8 as well as with hyperlipidemia. 9 Na + / Li + CT activity has been found to correlate significantly with several plasma lipid components, such as total cholesterol, trigly cerides (TG) (positive correlation), and high-density lipoprotein (HDL) cholesterol (inverse correlation), [9][10][11] and can be modulated by lipid-lowering strategies, including exercise, dietary intervention, and fibrates.…”

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confidence: 99%

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Effects of Atorvastatin on Red-blood Cell Na+/Li+ Countertransport in Hyperlipidemic Patients With and Without Hypertension

Kosmidou¹,

Hatzitolios²,

Adamidou³

et al. 2008

American Journal of Hypertension

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BACKGROUNDTo explore the effect of short-term cholesterol-lowering treatment with atorvastatin on erythrocyte sodium-lithium countertransport (Na + /Li + CT) activity. methODs Group A consisted of 30 patients (14 men) with mild essential hypertension (systolic blood pressure (SBP), 140-159 mm Hg and/or diastolic BP, 90-99 mm Hg) and primary hypercholesterolemia lowdensity lipoprotein (LDL) cholesterol >4.1 mmol/l and triglycerides (TG) <2.8 mmol/l), group B of 30 normotensive patients (16 men) with primary hypercholesterolemia, while 37 (18 men) healthy volunteers comprised the control group. After a 6-week dietary lead-in, all eligible patients were prescribed 20 mg/day of atorvastatin. Anthropometric data, blood-pressure (BP) measurements and determinations of lipid, non-lipid metabolic parameters (including homeostasis model assessment index, (HOMA-IR)) and erythrocyte Na + /Li + CT activity were collected at baseline and after 12 weeks of treatment. ResUltsAt baseline Na + /Li + CT activity was significantly higher in group A and B compared with the control group and correlated directly with obesity indices, systolic and diastolic BP, total cholesterol, LDLcholesterol, TG, apolipoprotein B (apoB), HOMA-IR, uric acid and inversely with high-density lipoprotein (HDL)-cholesterol and apoA1. Systolic and diastolic BP levels, HOMA-IR and Na + /Li + CT activity were significantly decreased after atorvastatin treatment in both patient groups. The reduction in Na + /Li + CT activity correlated with baseline Na + /Li + CT activity and the changes in HOMA-IR values. CONClUsiONsShort-term treatment with atorvastatin for patients with hypercholesterolemia, and with or without essential hypertension, is associated with a significant reduction in the erythrocyte Na + /Li + CT activity, BP levels and insulin resistance independent of concomitant changes in lipid parameters.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of Atorvastatin on Red-blood Cell Na+/Li+ Countertransport in Hyperlipidemic Patients With and Without Hypertension

Kosmidou¹,

Hatzitolios²,

Adamidou³

et al. 2008

American Journal of Hypertension

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“…The lithium efflux occurs mainly through an electrically neutral pump called Na + -Li + counter-transporter (el-Mallakh 2004), which in vivo exchanges sodium for sodium, but also accepts lithium (Vaccaro et al 2005). Lithium ions may replace sodium ions in this system and be transported via this carrier across the cell membrane in both directions (Mallinger et al 1997).…”

Section: Lithium Transport Across Cell Membranementioning

confidence: 99%

Lithium – therapeutic tool endowed with multiple beneficiary effects caused by multiple mechanisms

Vošahlíková¹,

Svoboda²

2016

Acta Neurobiologiae Experimentalis

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Mood disorders are relatively common serious human diseases for which there is often no ideal pharmacotherapy. Basic characteristic of these diseases is affective disorder shifting the mood of the patient to depression (together with anxiety or not) or towards to euphoria. Available drugs are usually divided into two groups -mood stabilizers, which are used primarily to treat bipolar disorder, and antidepressants for the treatment of unipolar depression. Lithium is still recommended as the first choice for dealing with bipolar disorder. Despite abundant clinical use of mood stabilizing drugs, important questions regarding their mechanism of action remain open.In this paper we present the brief review of rather diversified hypotheses and ideas about mechanisms of genesis of mood disorders and lithium interferences with these pathological states. New data derived from the high-resolution crystallographic studies of allosteric,

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“…Sodium/lithium countertransport is a highly heritable trait that was linked to the development of essential hypertension and diabetes in humans [25][26][27][28]. In line with these studies and a potential role in insulin secretion, NHA2 mRNA and protein are expressed in rodent b-cell lines [5 && ,24,29], as well as in murine and human primary b cells [5 && ].…”

Section: Role Of Nha2 In B Cellsmentioning

confidence: 99%

Role of Na/H exchange in insulin secretion by islet cells

Deisl

Albano

Fuster

2014

Current Opinion in Nephrology and Hypertension

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Purpose of review Sodium/hydrogen exchangers (NHEs) are a large family of transport proteins catalyzing the exchange of cations for protons across lipid bilayer membranes. Several isoforms are expressed in b cells of the endocrine pancreas, including the recently discovered and poorly characterized isoform NHA2. This review will summarize advances in our understanding of the roles of NHEs in the regulation of insulin secretion in b cells. Recent findingsPlasmalemmal full-length NHE1 defends b cells from intracellular acidification, but has no role in stimulussecretion coupling and is not causally involved in glucose-induced alkalinization of the b cell. The function of a shorter NHE1 splice variant, which localizes to insulin-containing large dense core vesicles, remains currently unknown. In contrast, in-vitro and in-vivo studies indicate that the NHA2 isoform is required for insulin secretion and clathrin-mediated endocytosis in b cells. SummaryRecent data highlight the importance of NHEs in the regulation of cellular pH, clathrin-mediated endocytosis and insulin secretion in b cells. Based on these studies, a pathophysiological role of NHEs in human disorders of the endocrine pancreas seems likely and should be investigated.

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Enhanced Na–Li countertransport: a marker of inherited susceptibility to type 2 diabetes

Abstract: Prospective data from the present study show for the first time enhanced Na-Li CT activity is a significant predictor of development of diabetes in adults, thus suggesting that it could be viewed as a pre-clinical, possibly genetic, marker of inherited susceptibility to type 2 diabetes.

Cited by 9 publications

References 33 publications

Effects of Atorvastatin on Red-blood Cell Na+/Li+ Countertransport in Hyperlipidemic Patients With and Without Hypertension

Effects of Atorvastatin on Red-blood Cell Na+/Li+ Countertransport in Hyperlipidemic Patients With and Without Hypertension

Lithium – therapeutic tool endowed with multiple beneficiary effects caused by multiple mechanisms

Role of Na/H exchange in insulin secretion by islet cells

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