Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus

Lee, C. T.; Lien, Yeong‐Hau H.; Lai, Li‐Wen; Chen, J. B.; Lin, Chung Ren; Chen, H. C.

doi:10.1038/sj.ki.5000344

Cited by 65 publications

(59 citation statements)

References 38 publications

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“…However, these differences may be explained by the dietary Mg 2+ intake of the subjects, since patients in the original study showed reduced Mg 2+ intake (,250 mg/day) (71). The mRNA expression of TRPM6 is changed in diabetic rats, although results are contradictory and may depend on the experimental model used (96,97). Whereas some report increased TRPM6 expression (96), others show that TRPM6 is downregulated (97).…”

Section: Trpm6mentioning

confidence: 95%

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: Trpm6mentioning

confidence: 95%

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

et al. 2015

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“…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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“…Similarly, rats with experimentally induced diabetes display a significant increase in the fractional excretion of Ca 2+ [41]. However, these diabetic rats showed increased mRNA and protein levels of both TRPV5 and calbindin-D 28K .…”

Section: Clinical Relevancementioning

confidence: 99%

Active Ca2+ reabsorption in the connecting tubule

Boros

Bindels

Hoenderop

2008

Pflugers Arch - Eur J Physiol

114

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The kidney plays a crucial role in the maintenance of the body calcium (Ca 2+ ) balance. Ca 2+ is an essential ion in all organisms and participates in a large variety of structural and functional processes. In mammals, active tubular Ca 2+ reabsorption is restricted to the distal part of the nephron, i.e., the late distal convoluted (DCT2) and the connecting tubules (CNT), where approximately 10-15% of the total Ca 2+ is reabsorbed. This active transcellular transport is hallmarked by the transient receptor potential vanilloid 5 (TRPV5) epithelial Ca 2+ channel, regulated by an array of events, and mediated by hormones, including 1,25-dihydroxyvitamin D 3 , parathyroid hormone, and estrogen. Novel molecular mechanisms have been identified, such as the direct regulatory effects of klotho and tissue kallikrein on the abundance of TRPV5 at the apical membrane. The newly discovered mechanisms could provide potential pharmacological targets in the therapy of renal Ca 2+ wasting. This review discusses the three basic molecular steps of active Ca 2+ reabsorption in the DCT/CNT segments of the nephron, including apical entry, cytoplasmic transport, and basolateral extrusion of Ca 2+ . In addition, an overview of the recently identified mechanisms governing this active Ca 2+ transport through the DCT2/CNT epithelial cells will be presented.

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Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus

Cited by 65 publications

References 38 publications

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

Hypomagnesemia in Patients with Type 2 Diabetes

Active Ca2+ reabsorption in the connecting tubule

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