Association of increased renal &lt;i&gt;Cyp24a1&lt;/i&gt; gene expression with low plasma 1,25-dihydroxyvitamin D levels in rats with streptozotocin-induced diabetes

Tajiri, Mari; Nakahashi, Otoki; Kagawa, Tomohiro; Masuda, Masashi; Ohminami, Hirokazu; Iwano, Masayuki; Takeda, Eiji; Taketani, Yutaka; Yamamoto, Hironori

doi:10.3164/jcbn.19-79

Cited by 13 publications

(7 citation statements)

References 37 publications

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“…This is in contrast with a previous study reporting that the plasma 1α,25(OH) 2 D decreases in the diabetic mice by 60% ( 32 ). On the other hand, similar to an earlier short-term study in rat, we observed that 4 weeks of STZ-induced diabetes increases the expression of the vitamin D catabolic enzyme Cyp24a1 in the kidney ( 33 ). After 13 weeks, the expression was normalized.…”

Section: Discussionsupporting

confidence: 90%

Streptozotocin-induced Diabetes Represses Hepatic CYP2R1 Expression but Induces Vitamin D 25-Hydroxylation in Male Mice

2022

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Vitamin D deficiency (i.e., low plasma 25-hydroxyvitamin D (25-OH-D)) associates with the prevalence of metabolic diseases including type 1 diabetes, however, the molecular mechanisms are incompletely understood. Recent studies have indicated that both fasting and metabolic diseases suppress the cytochrome P450 (CYP) 2R1, the major hepatic vitamin D 25-hydroxylase. We now specifically studied the effect of a mouse model of type 1 diabetes on the regulation of Cyp2r1 and vitamin D status. We show that streptozotocin-induced diabetes in mice suppresses the expression of the Cyp2r1 in the liver. While insulin therapy normalized the blood glucose levels in the diabetic mice, it did not rescue the diabetes-induced suppression of Cyp2r1. Similar regulation of Cyp2r1 was observed also in the kidney. Plasma 25-OH-D level was not decreased, and was, in contrast, higher after 4 and 8 weeks of diabetes. Furthermore, the vitamin D 25-hydroxylase activity was increased in the livers of the diabetic mice suggesting compensation of the Cyp2r1 repression by other vitamin D 25-hydroxylase enzymes. Cyp27b1, the vitamin D 1α-hydroxylase, expression in the kidney and the plasma 1α,25-dihydroxyvitamin D level were higher after 4 weeks of diabetes, while both were normalized after 13 weeks. In summary, these results indicate that in the mouse model of type 1 diabetes suppression of hepatic Cyp2r1 expression does not result in reduced hepatic vitamin D 25-hydroxylase activity and vitamin D deficiency. This may be due to induction of other vitamin D 25-hydroxylase enzymes in response to diabetes.

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Section: Discussionsupporting

confidence: 90%

Streptozotocin-induced Diabetes Represses Hepatic CYP2R1 Expression but Induces Vitamin D 25-Hydroxylation in Male Mice

2022

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“…The lower levels of 25(OH)D could have been partly induced by the status of diseases with fewer outdoor activities. Moreover, a recent study ( 40 ) found that the plasma 1,25(OH) 2 D levels decreased in streptozotocin-induced diabetes rats, in which high Cyp24a1 expression levels may play an important role.…”

Section: Discussionmentioning

confidence: 99%

Effect of vitamin D supplementation on glycose homeostasis and islet function in vitamin D deficient or insufficient diabetes and prediabetes: a systematic review and meta-analysis

Zou

Guo

et al. 2021

J. Clin. Biochem. Nutr.

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Objective of the present study was to evaluate the effect of vitamin D supplementation on glycose homeostasis, islet function, and diabetes progress. Literatures were searched via electronic databases, websites, and previous reviews from the earliest available time to the end of May 2020. Randomized controlled trials initially designed for diabetes and prediabetes with 25dihydroxyvitamin D [25(OH)D]<30 ng/ml were included. All data were analyzed and presented based on the Cochrane guidelines and PRISMA guidelines. In total, 27 articles (n = 1,932) were enrolled in this study. Vitamin D supplementation significantly improved fasting blood glucose, postprandial blood glucose, and quantitative insulin sensitivity check index in diabetes and prediabetes with baseline 25(OH)D<30 ng/ml. Higher percentages regressing from prediabetes to normal glucose status [1.60 (1.19, 2.17), p = 0.002, n = 564] and lower percentage progressing from prediabetes to diabetes [0.68 (0.36, 1.27), p = 0.23, n = 569] were found in the supplementation group. The positive effects of vitamin D supplementation on body mass index, waist, HDL-C, LDL-C, and CRP were also demonstrated. In conclusion, modest improvements in vitamin D supplementation on short-term glycose homeostasis, insulin sensitivity, and disease development in diabetes and prediabetes with 25(OH)D<30 ng/ml were demonstrated, but more research needs to be conducted in the future to support the clinical application. (Register ID: CRD42020186004)

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“…TRPV5 is a calcium channel which mediates calcium reabsorption in the kidney and plays an important role in the regulation of urinary calcium ( 33 ). Studies have reported elevated urinary calcium levels along with decreased renal TRPV5 expression in diabetes ( 34 , 35 ). Studies have also shown that decreased renal TRPV5 expression was associated with reduced renal calcium reabsorption ( 36 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

Investigating the Effects of Diet-Induced Pre-Diabetes on the Functioning of Calcium-Regulating Organs in Male Sprague Dawley Rats: Effects on Selected Markers

2022

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Derangements to the functioning of calcium-regulating organs have been associated with type 2 diabetes mellitus (T2DM), a condition preceded by pre-diabetes. Type 2 diabetes has shown to promote renal calcium wastage, intestinal calcium malabsorption and increased bone resorption. However, the changes to the functioning of calcium-regulating organs in pre-diabetes are not known. Subsequently, the effects of diet-induced pre-diabetes on the functioning of calcium-regulating organs in a rat model for pre-diabetes was investigated in this study. Male Sprague Dawley rats were separated into two groups (n=6, each group): non-pre-diabetic (NPD) group and a diet-induced pre-diabetic (DIPD) group for 20 weeks. After the experimental period, postprandial glucose and HOMA-IR were analysed in addition to plasma and urinary calcium concentrations. Gene expressions of intestinal vitamin D (VDR), intestinal calbindin-D9k, renal 1-alpha hydroxylase and renal transient receptor potential vanilloid 5 (TRPV5) expressions in addition to plasma osteocalcin and urinary deoxypyridinoline concentrations were analysed at week 20. The results demonstrated significantly increased concentrations of postprandial glucose, HOMA-IR and urinary calcium in addition to unchanged plasma calcium levels in the DIPD group by comparison to NPD. Renal TRPV5, renal 1-alpha hydroxylase, intestinal VDR and intestinal calbindin-D9k expressions were increased in the DIPD group by comparison to NPD. Furthermore, plasma osteocalcin levels were increased and urine deoxypyridinoline levels were decreased in the DIPD group by comparison to NPD. These observations may suggest that calcium-regulating organs compensate for the changes to calcium homeostasis by inducing increased renal calcium reabsorption, increased intestinal calcium absorption and decreased bone resorption followed by increased bone formation.

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Association of increased renal <i>Cyp24a1</i> gene expression with low plasma 1,25-dihydroxyvitamin D levels in rats with streptozotocin-induced diabetes

Cited by 13 publications

References 37 publications

Streptozotocin-induced Diabetes Represses Hepatic CYP2R1 Expression but Induces Vitamin D 25-Hydroxylation in Male Mice

Streptozotocin-induced Diabetes Represses Hepatic CYP2R1 Expression but Induces Vitamin D 25-Hydroxylation in Male Mice

Effect of vitamin D supplementation on glycose homeostasis and islet function in vitamin D deficient or insufficient diabetes and prediabetes: a systematic review and meta-analysis

Investigating the Effects of Diet-Induced Pre-Diabetes on the Functioning of Calcium-Regulating Organs in Male Sprague Dawley Rats: Effects on Selected Markers

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