The Role of Osteopontin in the Pathogenesis and Complications of Type 1 Diabetes Mellitus in Children

Abstract

Objective:Type 1 diabetes mellitus (T1DM) is the most common chronic metabolic disorder of childhood and adolescence. Osteopontin plays a significant role in the development and progression of several autoimmune diseases. Moreover, osteopontin promotes adipose tissue inflammation, dysfunction, and insulin resistance. To investigate the levels of serum osteopontin in pediatric patients with T1DM and to explore if these levels have a role in the prediction of diabetes complications.Methods:This was a case–control study conducted at the Endocrinology unit of the Children’s Hospital of Zagazig University in Egypt, from October 2014 to December 2015. Sixty patients with T1DM and 60 healthy subjects were enrolled. A detailed medical history was taken from all patients/parents. A full clinical examination including ophthalmoscopy was performed on all patients. Fasting blood glucose, hemoglobin A1c (HbA1c), urine albumin/creatinine ratio, and serum osteopontin levels were also determined in all subjects.Results:Patients with T1DM had significantly higher serum osteopontin levels compared with controls (mean ± standard deviation: 13.7±3.4 μg/L vs. 8.9±2.9 μg/L, p<0.001). Also, serum osteopontin concentrations were higher in patients with microalbuminuria than in patients with normal albumin excretion rate and in the control group. Similarly, those who had retinal disease had higher osteopontin concentrations than those without (16.8±2 vs. 12.4±3 mg/L; p=0.005). Serum osteopontin levels correlated with a diagnosis of T1DM, and in diabetic patients, correlated with higher systolic and diastolic blood pressure, body mass index values and with lower high density lipoprotein values, diagnosis of retinopathy, and microalbuminuria. No correlation was found between osteopontin levels and HbA1c, insulin dose, co-medications, and diabetes duration in T1DM patients. The association between high osteopontin levels and T1DM was independent from all confounders.Conclusion:This study shows that increased osteopontin levels are independently associated with T1DM in pediatric patients and supports the hypothesis that osteopontin may have a role in the prediction of microvascular diabetes complications.

Alterations of morphology and phosphorylated protein expression in the seminal vesicles of diabetic mice

“…Tyrosine-phosphorylated proteins are specifically localised within testicular tissue (Arad-Dann, Beller, Haimovitch, Gavrieli, & Ben-Sasson, 1993;Chaichun et al, 2017) and are assumed to play a role in spermatogenesis (Arun, Burawat, Sukhorum, Sampannang, Maneenin, et al, 2016;Arun, Burawat, Sukhorum, Sampannang, Uabundit, et al, 2016;Iamsaard et al, 2014;Sampannang et al, 2017Sampannang et al, , 2018 F I G U R E 6 Representative immuno-Western blot of tyrosine-phosphorylated proteins in seminal lysates (a), and intensity of a 72 kDa tyrosine-phosphorylated proteins expressed in the seminal vesicle compared among type 1 DM control (C-T1DM), type 1 DM (T1DM), type 2 DM control (C-T2DM) and type 2 DM (T2DM) mice on experimental days 36 (b). **p < .05 compared between T1DM and T2DM 2013; Talat et al, 2016). β-actin was used as an internal control.…”

“…Epidermal-like growth factor (EGF) was used as a positive control and bovine serum albumin (BSA) was used as a negative control. Thus, monitoring for significant increases in OPN may help to predict microvascular diabetes complications (Talat et al, 2016). Data are represented as mean ± SD.…”

“…Protein phosphorylation is a post-translational process of most cellular modifications including sperm physiological capacitation and acrosome exocytosis (Salicioni et al, 2007;Shivaji et al, 2007;Stival et al, 2016). Tyrosine-phosphorylated proteins are specifically localised within testicular tissue (Arad-Dann, Beller, Haimovitch, Gavrieli, & Ben-Sasson, 1993;Chaichun et al, 2017) and are assumed to play a role in spermatogenesis (Arun, Burawat, Sukhorum, Sampannang, Maneenin, et al, 2016;Arun, Burawat, Sukhorum, Sampannang, Uabundit, et al, 2016;Iamsaard et al, 2014;Sampannang et al, 2017Sampannang et al, , 2018 2013; Talat et al, 2016). Thus, monitoring for significant increases in OPN may help to predict microvascular diabetes complications (Talat et al, 2016).…”

Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases

“…This destruction is preceded by insulitis, a massive invasion of the islets by a mixed population of lymphocytes and macrophages. OPN may play a role in this inflammation since serum levels are increased in T1DM compared to controls and in diabetic patients correlated with high systolic and diastolic blood pressure, body mass index, low high density lipoprotein, diagnosis of retinopathy, and microalbuminuria [164, 165]. High OPN concentrations are associated with an unfavorable metabolic profile in these patients and are strong predictors of incipient diabetic nephropathy [164, 166].…”

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

“…Therefore, several studies have been performed to assess the association of OPN and predisposition to T1D. This protein has been found to be elevated in pediatric and adult patients with T1D [104][105][106]. Moreover, OPN has correlated with some clinical and biochemical parameters in T1D patients, including higher body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), lower high-density lipoprotein (HDL), and microalbuminuria [104,107].…”