Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects

Haap, Michael; Heller, Emanuela; Thamer, Claus; Tschritter, Otto; Stefan, Norbert; Fritsche, Andreas

doi:10.1038/sj.ejcn.1602375

Cited by 85 publications

(85 citation statements)

References 23 publications

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“…Phosphate depletion is thought to induce insulin resistance. Insulin resistance is associated with low serum phosphate in a population study on nondiabetic individuals [29]. The prevalence of type 2 diabetes or impaired glucose tolerance is elevated in primary hyperparathyroidism, possibly via hypophosphatemia [30,31].…”

Section: Discussionmentioning

confidence: 99%

Evidence against a direct role of klotho in insulin resistance

Lorenzi

Veyrat-Durebex

Wollheim

et al. 2009

Pflugers Arch - Eur J Physiol

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The klotho gene may be involved in the aging process. Klotho is a coactivator of FGF23, a regulator of phosphate and vitamin D metabolism. It has also been reported to be downregulated in insulin resistance syndromes and paradoxically to directly inhibit IGF-1 and insulin signaling. Our aim was to study klotho's regulation and effects on insulin and IGF-1 signaling to unravel this paradox. We studied klotho tissue distribution and expression by quantitative real-time polymerase chain reaction and Western blotting in obese Zucker rats and high-fat fed Wistar rats, two models of insulin resistance. Klotho was expressed in kidneys but at much lower levels (<1.5%) in liver, muscle, brain, and adipose tissue. There were no significant differences between insulin resistant and control animals. We next produced human recombinant soluble klotho protein (KLEC) and studied its effects on insulin and IGF-1 signaling in cultured cells. In HEK293 cells, FGF23 signaling (judged by FRS2-α and ERK1/2 phosphorylation) was activated by conditioned media from KLECproducing cells (CM-KLEC); however, IGF-1 signaling was unaffected. CM-KLEC did not inhibit IGF-1 and insulin signaling in L6 and Hep G2 cells, as judged by Akt and ERK1/2 phosphorylation. We conclude that decreased klotho expression is not a general feature of rodent models of insulin resistance. Further, the soluble klotho protein does not inhibit IGF-1 and/or insulin signaling in HEK293, L6, and HepG2 cells, arguing against a direct role of klotho in insulin signaling. However, the hypothesis that klotho indirectly regulates insulin sensitivity via FGF23 activation remains to be investigated.

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Section: Discussionmentioning

confidence: 99%

Evidence against a direct role of klotho in insulin resistance

Lorenzi

Veyrat-Durebex

Wollheim

et al. 2009

Pflugers Arch - Eur J Physiol

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“…Phosphorus is a vital mineral that is involved in various metabolic processes, especially that of glucose and energy (Haap et al 2006, Lippi et al 2009). Following feeding, low serum phosphate concentration is related to increased blood glucose level and decreased insulin sensitivity (Friedman 2007).…”

Section: Discussionmentioning

confidence: 99%

Starvation and refeeding in rats: effect on some parameters of energy metabolism and electrolytes and changes of hepatic tissue

et al. 2016

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Regarding the importance of starvation and refeeding and the occurrence of refeeding syndrome in various conditions, the present study was conducted to investigate the effects of refeeding on some parameters of energy metabolism and electrolytes and changes of hepatic tissue in male Wistar rats. Fifty-seven rats were divided into six groups, having 6 to 11 rats. Food was provided ad-libitum until three months and then the first group was considered without starvation (day 0). Other rats were fasted for two weeks. Group 2 was applied to a group immediately after starvation (day 14). Groups 3 to 6 were refed in days 16 till 22, respectively. At the end of each period, blood and tissue samples were taken and histopathological and serum analysis, including serum electrolytes (calcium, phosphorus, sodium, potassium), the energy parameters (glucose, insulin, cortisol) and the liver enzymes (ALT, AST, ALP) were determined. Insulin decreased by starvation and then showed an increasing trend compared to starvation period, which the highest amount of this parameter was observed eight days post-refeeding. Serum glucose level showed the opposite pattern of insulin. Histopathological examination of the tissue sections revealed clear vacuoles after starvation and refeeding, in which the severity of lesions gradually decreased during refeeding. The cortisol level decreased by starvation and then increased during refeeding. Also, potassium and phosphorus concentrations declined by refeeding and the serum sodium and potassium levels were changed in the relatively opposite manner. The calcium level decreased by starvation and then increased during refeeding. These results could help recognize and remedy the refeeding syndrome.

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“…11 Furthermore, among patients with a family history of type 2 diabetes, serum phosphate levels were significantly negatively correlated with glucose tolerance. 12 Data also indicate significant negative correlations between serum phosphate and body mass index and waist-to-hip ratio. 13 Among patients who entered a lifestyle modification program for cardiovascular risk reduction, serum phosphate was significantly negatively correlated with systolic BP.…”

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confidence: 90%