School of laboratory Medicine and Medical Sciences, Discipline of Human Physiology, University of KwaZulu-Natal, KwaZulu- Natal, South Africa.
Front Endocrinol (Lausanne). 2022 Jul 11;13:914189. doi: 10.3389/fendo.2022.914189. eCollection 2022.
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.
钙调节器官功能障碍与 2 型糖尿病(T2DM)有关,2 型糖尿病之前存在糖尿病前期。2 型糖尿病已显示可促进肾脏钙流失、肠道钙吸收不良和骨吸收增加。然而,糖尿病前期钙调节器官功能的变化尚不清楚。因此,本研究旨在研究饮食诱导的糖尿病前期对糖尿病前期大鼠模型中钙调节器官功能的影响。雄性 Sprague Dawley 大鼠分为两组(n=6,每组):非糖尿病前期(NPD)组和饮食诱导的糖尿病前期(DIPD)组,共 20 周。实验结束后,分析餐后血糖和 HOMA-IR,以及血浆和尿钙浓度。此外,还分析了第 20 周时肠道维生素 D(VDR)、肠道钙结合蛋白-D9k、肾脏 1-α羟化酶和肾脏瞬时受体电位香草醛 5(TRPV5)的基因表达以及血浆骨钙素和尿脱氧吡啶啉的浓度。结果表明,与 NPD 相比,DIPD 组餐后血糖、HOMA-IR 和尿钙浓度显著升高,而血浆钙水平不变。与 NPD 相比,DIPD 组的肾脏 TRPV5、肾脏 1-α羟化酶、肠道 VDR 和肠道钙结合蛋白-D9k 的表达增加。此外,与 NPD 相比,DIPD 组血浆骨钙素水平升高,尿脱氧吡啶啉水平降低。这些观察结果表明,钙调节器官可能通过诱导增加的肾脏钙重吸收、增加的肠道钙吸收和减少的骨吸收来代偿钙稳态的变化,随后增加骨形成。