Intravenous Magnesium Reduces the Rate of Glucose Disposal in Lactating Sheep

Abstract

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

Infusion of Mg in humans acutely reduces serum insulin levels: a pilot study

“…[24,25]). As found in sheep [12], the present work demonstrates in humans a reduction in circulating fasting insulin levels following an infusion of MgSO 4 . This decline in serum insulin may be due to impaired release of the hormone, since insulin secretion requires the presence of external Ca 2+ [26], and Mg 2+ is considered to be "Nature's physiologic calcium blocker" [27], and in studies using isolated pancreatic islets or perfused whole organs, inhibition of Ca 2+ influx by verapamil was also associated with a decrease in insulin secretion [28].…”

“…Infusion rates used in this study were based on those previously used for stroke patients [3]. Since the effect of magnesium on serum insulin levels was the major interest in this study, a power calculation using information based on the precision of the insulin ELISA indicated that to detect a change of 15% in paired insulin levels, six subjects would be required (␣=0.05, power=0.8); our previous experience [12] indicated that the fall in insulin was likely to be much larger than this, so six subjects were deemed sufficient for the study. Six healthy male volunteers (aged 28-43) were recruited from staff of the Hannah Research Institute, Ayr and Royal Infirmary of Edinburgh, and were free from hypertension, overt renal or liver disease, or diabetes.…”

“…All results are mean values±SEM. To minimise variability in the analysis of the response curves, graphs were expressed as percentages of mean pre-infusion (basal) levels [12], and analysed by repeated measures 1-way ANOVA, with Bonferroni's Multiple Comparison correction for comparisons between multiple points. Differences between basal values and those occurring at maximum serum Mg 2+ were examined by Student's paired t test.…”

“…Subclinical systemic effects unrelated to the original therapeutic targets of Mg, and which arise from infusion of supraphysiological levels of the divalent cation remain largely undocumented, although some evidence suggests a potential interaction with insulin: in vitro, elevating external Mg decreased calcium uptake into islets isolated from rats [9] or ob/ob mice [10], whereas in humans, hypermagnesaemia induced by Mg infusion led to a reduction in the level of insulin reached during an intravenous glucose-tolerance test [11]. In lactating and non-lactating sheep, infusion of Mg decreased circulating insulin levels, and in the lactating animals, impaired glucose disposal during an intravenous glucose-tolerance test [12]. Finally, in a rat model of thyrotoxicosis, parenteral Mg infusion decreased insulin secretion [13].…”

Apical sodium–glucose co-transport can be regulated by blood-borne glucose in the ruminal epithelium of sheep (Ovis aries, Merino breed)

“…fat genotype sheep; Francis et al 1999) and reproductive stage (lactators . non-lactators; El-Sherif & Assad, 2001;Gow et al 2003).…”