Insulin stimulates Na+, Cl-, Ca2+, and Mg2+ transports in TAL of mouse nephron: cross-potentiation with AVP

Mandon, B.; Siga, Esteban; Chabardès, Danielle; Firsov, Dmitri; Roinel, N.; Rouffignac, C. de

doi:10.1152/ajprenal.1993.265.3.f361

Cited by 53 publications

(51 citation statements)

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“…However, it was not until the 1960s, when synthetic insulin was available and Mg 2+ measurements were improved, that it became apparent that insulin regulates Mg 2+ reabsorption in the kidney (91). Indeed, microperfusion experiments in mouse TAL segments show increased Mg 2+ permeability after insulin stimulation (92). Moreover, in mouse DCT cells insulin stimulates Mg 2+ uptake (93).…”

Section: Insulin Vesicle Releasementioning

confidence: 99%

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

et al. 2015

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Over the past decades, hypomagnesemia (serum Mg 2+ <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg 2+ on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM.Globally, over 300 million people suffer from type 2 diabetes mellitus (T2DM), and the prevalence is predicted to rise to over 600 million over the next decades (1). T2DM is characterized by a combination of insulin deficiency and insulin resistance. The general pathophysiological concept is that hyperglycemia emerges when endogenous insulin secretion can no longer match the increased demand owing to insulin resistance (2).Since the 1940s, it has been reported that T2DM is associated with hypomagnesemia (3,4). Low serum magnesium (Mg 2+ ) levels have been reported in large cohorts of patients with T2DM (5). In T2DM, the prevalence of hypomagnesemia ranges between 14 and 48% compared with between 2.5 and 15% in healthy control subjects (4). Hypomagnesemia is associated with a more rapid, and permanent, decline in renal function in patients with T2DM (6). In addition, epidemiological studies consistently show an inverse relationship between dietary Mg 2+ intake and risk of developing T2DM (7). Several patient studies have shown beneficial effects of Mg 2+ supplementation on glucose metabolism and insulin sensitivity (8-10). Recently, Rodríguez-Morán et al. (11) published an excellent overview of the clinical studies addressing the role of Mg 2+ in T2DM. In our review, we will focus on the molecular mechanisms underlying these clinical observations. Mg 2+ is an essential ion for human health, as it is involved in virtually every mechanism in the cell, including energy homeostasis, protein synthesis, and DNA stability (12). Considering these divergent functions, it can be appreciated that serum Mg 2+ levels are tightly regulated between 0.7 and 1.05 mmol/L in healthy individuals. However, impaired intestinal Mg 2+ absorption or renal Mg 2+ wasting can lead to hypomagnesemia. A wide range of genetic and environmental factors can affect the Mg 2+ -deficient state, which have previously been extensively reviewed (12).In this review, we address the following questions that are central to the role of hypomagnesemia in T2DM: 1) Does Mg 2+ regulate insulin secretion? 2) How does Mg 2+ affect insulin resistance? 3) How does insulin regulate Mg 2+ homeostasis? Taken together, these questions will aid the understanding of whether hypomagnesemia is a causative factor for or a consequence of T2DM.

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Section: Insulin Vesicle Releasementioning

confidence: 99%

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

et al. 2015

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“…Parathyroid hormone, calcitonin, glucagon, and antidiuretic hormone have been suggested to enhance Mg transport in the TAL via the second messenger cAMP (55). Insulin also has been implicated to play a role at this nephron segment by increasing the favorable transepithelial potential difference for Mg reabsorption (58).…”

Section: Renal Metabolismmentioning

confidence: 99%

“…Because insulin has been implicated in enhancing Mg reabsorption at the TAL, insulin deficiency or resistance in the diabetic state can promote Mg wasting at this nephron segment (58). The expression of paracellin 1 in TAL, however, has not been shown to be increased in diabetic rats (66).…”

Section: Renal Causesmentioning

confidence: 99%

Hypomagnesemia in Patients with Type 2 Diabetes

Pham

Pham³

et al. 2007

Clinical Journal of the American Society of Nephrology

356

339

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Hypomagnesemia has been reported to occur at an increased frequency among patients with type 2 diabetes compared with their counterparts without diabetes. Despite numerous reports linking hypomagnesemia to chronic diabetic complications, attention to this issue is poor among clinicians. This article reviews the literature on the metabolism of magnesium, incidence of hypomagnesemia in patients with type 2 diabetes, implicated contributing factors, and associated complications. Hypomagnesemia occurs at an incidence of 13.5 to 47.7% among patients with type 2 diabetes. Poor dietary intake, autonomic dysfunction, altered insulin metabolism, glomerular hyperfiltration, osmotic diuresis, recurrent metabolic acidosis, hypophosphatemia, and hypokalemia may be contributory. Hypomagnesemia has been linked to poor glycemic control, coronary artery diseases, hypertension, diabetic retinopathy, nephropathy, neuropathy, and foot ulcerations. The increased incidence of hypomagnesemia among patients with type 2 diabetes presumably is multifactorial. Because current data suggest adverse outcomes in association with hypomagnesemia, it is prudent to monitor magnesium routinely in this patient population and treat the condition whenever possible.

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“…Na + ,K + -ATPase activity in MTAL results mostly from a continuous stimulation through the cAMP-PKA-dependent pathway and regulatory inhibition [13]. In rat MTAL, insulin displays a small stimulatory effect on Na + reabsorption [14] probably due to poor expression of insulin receptors [15]. In addition, insulin does not stimulate Na + ,K + -ATPase activity in the thick ascending limb [16].…”

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confidence: 99%

C-Peptide stimulates Na+,K+-ATPase activity via PKC alpha in rat medullary thick ascending limb

et al. 2003

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Aims/hypothesis. C-peptide, the cleavage product of proinsulin processing exerts physiological effects including stimulation of Na + ,K + -ATPase in erythrocytes and renal proximal tubules. This study was undertaken to assess the physiological effects of connecting peptide on Na + ,K + -ATPase activity in the medullary thick ascending limb of Henle's loop. Methods. Na + ,K + -ATPase activity was measured as the ouabain-sensitive generation of 32 Pi from γ[ 32 P]-ATP and 86 Rb uptake on isolated rat medullary thick ascending limbs. The cell-surface expression of Na + ,K + -ATPase was evaluated by Western blotting of biotinylated proteins, and its phosphorylation amount was measured by autoradiography. The membrane-associated fraction of protein kinase C isoforms was evaluated by Western blotting. Results. Rat connecting peptide concentration-dependently stimulated Na + ,K + -ATPase activity with a threshold at 10 −9 mol/l and a maximal effect at 10 −7 mol/l. C-peptide (10 −7 mol/l) already stimulates Na + ,K + -ATPase activity after 5 min with a plateau from 15 to 60 min. C-peptide (10 −7 mol/l) stimulated Na + ,K + -ATPase activity and 86 Rb uptake to the same extent, but did not alter Na + ,K + -ATPase cell surface expression. The stimulation of Na + ,K + -ATPase activity was associated with an increase in Na + ,K + -ATPase α-subunit phosphorylation and both effects were abolished by a specific protein kinase C inhibitor. Furthermore, connecting peptide induced selective membrane translocation of PKC-α. Conclusion/interpretation. This study provides evidence that in rat medullary thick ascending limb, C-peptide stimulates Na + ,K + -ATPase activity within a physiological concentration range. This effect is due to an increase in Na + ,K + -ATPase turnover rate that is most likely mediated by protein kinase C-α phosphorylation of the Na + ,K + -ATPase α-subunit, suggesting that C-peptide could control Na + reabsorption during non-fasting periods. [Diabetologia (2003) 46:124-131]

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Insulin stimulates Na+, Cl-, Ca2+, and Mg2+ transports in TAL of mouse nephron: cross-potentiation with AVP

Cited by 53 publications

References 0 publications

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

Hypomagnesemia in Patients with Type 2 Diabetes

C-Peptide stimulates Na+,K+-ATPase activity via PKC alpha in rat medullary thick ascending limb

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