Insulin action Accumulation in vitro of Mg2+ and K+ in rat uterus: Ion pump activity

Lostroh, Ardis J.; Krahl, M. E.

doi:10.1016/0005-2736(73)90417-3

Cited by 71 publications

(27 citation statements)

References 16 publications

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“…A decrease in serum [Mg 2+ ] in the glucose-infused lactators, relative to saline infusion in the same animals, may have been due to the glucose-induced rise in insulin stimulating Mg 2+ disposal and depleting the extracellular fluid of Mg 2+ , since insulin has long been known to stimulate Mg uptake into a variety of tissues and cell types. Insulin promoted uptake of magnesium in rat uteri (Lostroh & Krahl, 1973), perfused rat hearts and isolated cardiac myocytes (Romani et al 2000), human blood platelets (Hwang et al 1993;Takaya et al 1998) and cultured mouse renal distal convoluted tubules (Dai et al 1999). Furthermore, total plasma Mg concentration fell during euglycaemic hyperinsulinaemic glucose clamp in patients with essential hypertension, except when Mg was co-infused (Paolisso et al 1993).…”

Section: Magnesiummentioning

confidence: 99%

Intravenous Magnesium Reduces the Rate of Glucose Disposal in Lactating Sheep

Gow

Mitchell

Wait

2003

Experimental Physiology

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Magnesium deficiency is generally associated with an impaired ability to dispose of glucose. In order to test whether or not increasing the peripheral free Mg concentration ([Mg 2+ ]) would enhance glucose disposal, we have carried out glucose infusions in sheep with and without simultaneous infusion of Mg. Basal plasma glucose levels were higher in lactating sheep ('lactators') than in non-lactating sheep (controls) (P < 0.05). The glucose disposal rate (K G ) with no added Mg was greater in lactators than controls (P < 0.05). When Mg was added to the infusate, K G in lactators was reduced (P < 0.005). Infusion of Mg depressed basal insulin levels in controls and lactators (P < 0.0001 for both). The insulin response to the intravenous glucose tolerance test (IVGTT) was lower in lactators compared with controls (P < 0.0001); however, after correcting for the reduced basal insulin level when Mg was included during the IVGTT, there was no difference between the two groups. We conclude that intravenous Mg at the doses used in this study leads to a decrease in basal insulin secretion, and that increasing serum

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Section: Magnesiummentioning

confidence: 99%

Intravenous Magnesium Reduces the Rate of Glucose Disposal in Lactating Sheep

Gow

Mitchell

Wait

2003

Experimental Physiology

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“…Among the different hormones, insulin is an important modulator of the cellular content of magnesium [1,2], the most abundant intracellular divalent cation. Insulin-resistant patients have an impaired insulin-mediated erythrocyte magnesium accumulation [3][4][5] which correlates with a decrease in insulin sensitivity [3,4].…”

mentioning

confidence: 99%

“…On the other hand, magnesium is a cofactor of many enzymes involved in glucose metabolism, especially those using high energy phosphate bonds [6]. In vitro studies have shown that this cation has an important role in insulin action [1,7]. A relation-ship between hypomagnesaemia and insulin resistance has been reported among diabetic patients [8,9], and furthermore, chronic administration of magnesium has been found to improve the insulin sensitivity in non-insulin-dependent diabetic subjects [10] and in patients with severe hypomagnesaemia [11].…”

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confidence: 99%

Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats

Su�rez¹,

Pulido

Casla

et al. 1995

Diabetologia

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SummaryThe effect of magnesium deficiency on glucose disposal, glucose-stimulated insulin secretion and insulin action on skeletal muscle was investigated in rats which were fed a low magnesium-containing diet for 4 days. Control rats were fed a standard diet. Compared to the control rats, the rats fed with low magnesium diet presented: 1) lower serum magnesium levels (0.45 + 0.02 vs 0.78 + 0.01 mmol/1, p < 0.001), 2) higher basal serum glucose (6.8 +__ 0.2 vs 5.5 + 0.2 mmol/1, p < 0.05) and similar basal serum insulin, 3) 40 % reduction (p < 0.001) in the glucose disappearance rate after its i.v. administration, and 4) 45 % reduction (p < 0.05) in the glucose-stimulated insulin secretion. The insulin action upon the glucose uptake by skeletal muscle was determined by means of hindquarter perfusions. Compared with control rats, magnesium-deficient rats presented: 1) normal basal glucose uptake, 2) lower stimulatory effect on the glucose uptake by insulin at the concentrations of 5 x 10 -l~ mol/1 (3.0 + 0.9 vs 5.4 + 0.6, p < 0.05) and 5 x 10 -9 tool/1 (6.3 + 0.5 vs 8.0 + 0.5, p < 0.05), 3) normal glucose uptake at a maximal insulin concentration of i x 10 .7 mol/1, and 4) 50 % reduction in the insulin sensitivity (ED50:1.3 +_ 0.3 vs 0.55 + 0.1 mol/1, p < 0.05). In partially purified insulin receptors prepared from gastrocnemius muscle, 125I-insulin binding was similar in both groups of rats. However, the autophosphorylation of the fi-subunit of the insulin receptor was significantly reduced by 50 % in magnesium-deficient rats and the tyrosine kinase activity of insulin receptors toward the exogenous substrate Poly Glu4: Tyr 1 was also reduced (p < 0.05) by hypomagnesaemia. The abundance of the insulin-sensitive glucose transporter protein (muscle/fat GLUT4), measured by Western blot analysis using polyclonal antisera, was similar in muscles of control and hypomagnesaemic rats. These findings indicate that hypomagnesaemia has a deleterious effect on glucose metabolism due to an impairment of both insulin secretion and action. The insulin resistance observed in skeletal muscle of magnesium-deficient rats may be attributed, at least in part, to a defective tyrosine kinase activity of insulin receptors.

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“…Alternatively, the divalent cations, calcium and magnesium, have been proposed as possible second messengers for insulin (7)(8)(9)(10), with a large body of indirect evidence to support this theory. Krahl has reported that insulin caused an increased intracellular magnesium concentration in rat hemiuteri (11) and adipose tissue (12) and that calcium and magnesium were necessary for maximum insulin stimulation of protein synthesis (12). Agents which promote an increased concentration of intracellular calcium, such as ouabain, procaine, lanthanum, and calcium ionophores, have been reported to mimic the antilipolytic action of insulin (9,13,14).…”

mentioning

confidence: 99%

Ability of insulin to increase calcium binding by adipocyte plasma membranes.

McDonald¹,

Bruns²,

Jarett³

1976

Proc. Natl. Acad. Sci. U.S.A.

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Calcium specifically binds to adipocyte plasma membranes, demonstrating two classes of binding sites having affinity constants of 4.5 X 104 M-and 2.0 X 1O0 M-'. Insulin (100 microunits/ml) added directly to the isolated plasma membranes caused no alteration in calcium binding, whereas incubation of the adipocytes with 100 microunits/m of insulin resulted in a 25.0 k 1.6% increase in calcium binding to the subsequently isolated plasma membranes. The increase in calcium binding produced by insulin resulted from an increase in the maximum binding capacities of both classes of binding sites without alteration in their affinity constants. Additionally, a second pool of calcium in adipocyte plasma membranes has been identified by atomic absorption analysis; it was more than two times larger than the maximum binding capacity of the calcium binding system. This pool of calcium was stable, did not participate in the 45Ca2+ exchange, and was unaltered by insulin treatment. A similar stable pool of magnesium exists in plasma membranes and was also unaffected by insulin treatment. The increased capacity of the isolated plasma membranes to bind calcium after insulin treatment of the cells may represent an important bioregulating mechanism and supports the concept that calcium may play an important role in the effector system for insulin.The metabolic effects of insulin are thought to be produced by the interaction of insulin with its receptors on the plasma membranes (1, 2). This concept necessitates the involvement of a second messenger or an effector system to explain the mechanism of the complex cellular pleiotypic response to insulin. Considerable evidence suggests that adenosine 3':5'-cyclic monophosphate (cyclic AMP) does not fulfill the criteria of a second messenger for insulin in adipocytes (3, 4) and other cells (5, 6). Alternatively, the divalent cations, calcium and magnesium, have been proposed as possible second messengers for insulin (7-10), with a large body of indirect evidence to support this theory. Krahl has reported that insulin caused an increased intracellular magnesium concentration in rat hemiuteri (11) and adipose tissue (12) and that calcium and magnesium were necessary for maximum insulin stimulation of protein synthesis (12). Agents which promote an increased concentration of intracellular calcium, such as ouabain, procaine, lanthanum, and calcium ionophores, have been reported to mimic the antilipolytic action of insulin (9, 13, 14). Insulin was found to alter efflux of 45Ca2+ from preloaded fat pads and adipocytes (8, 10). Numerous intracellular enzymes have been reported to be both insulin and calcium sensitive (15)(16)(17)(18) (UDP glucose:glycogen 4-a-glucosyltransferase, EC 2.4.1.11) (18) isolated from adipocytes. Thus, small changes of calcium concentration at critical intracellular loci could have significant metabolic impact.The evaluation of cellular calcium distribution and regulation is difficult because intracellular calcium is highly compartmentalized with estimated concent...

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Insulin action Accumulation in vitro of Mg2+ and K+ in rat uterus: Ion pump activity

Cited by 71 publications

References 16 publications

Intravenous Magnesium Reduces the Rate of Glucose Disposal in Lactating Sheep

Intravenous Magnesium Reduces the Rate of Glucose Disposal in Lactating Sheep

Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats

Ability of insulin to increase calcium binding by adipocyte plasma membranes.

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