Intestinal alkaline phosphatase deficiency increases the risk of diabetes

Abstract

IntroductionOur previous case–control study demonstrated that a high level of intestinal alkaline phosphatase (IAP), an endotoxin-detoxifying anti-inflammatory enzyme secreted by villus-associated enterocytes and excreted with stool, plays a protective role against type 2 diabetes mellitus (T2DM) irrespective of obesity. In the current study, we investigated the long-term effect of IAP deficiency (IAPD) on the pathogenesis of T2DM.Research design and methodsA healthy cohort of participants without diabetes (30–60 years old), comprising 188 without IAPD (IAP level: ≥65 U/g stool) and 386 with IAPD (IAP level: <65 U/g stool), were followed up for 5 years. We measured stool IAP (STAP) and fasting plasma glucose, and calculated the risk ratio (RR) using log-binomial regression model.ResultsT2DM incidence rates were 8.0%, 11.7%, 25.6%, and 33.3% in participants with ‘persistent no IAPD’ (IAP level: always ≥65 U/g stool), ‘remittent IAPD’ (IAP level: increased from <65 U/g stool to ≥65 U/g stool), ‘persistent IAPD’ (IAP level: always <65 U/g stool), and ‘incident IAPD’ (IAP level: decreased from ≥65 U/g stool to <65 U/g stool), respectively. Compared with ‘persistent no IAPD’ the risk of developing T2DM with ‘incident IAPD’ was 270% higher (RR: 3.69 (95% CI 1.76 to 7.71), χ2 p<0.001). With ‘persistent IAPD’ the risk was 230% higher (RR: 3.27 (95% CI 1.64 to 6.50), p<0.001). ‘Remittent IAPD’ showed insignificant risk (RR: 2.24 (95% CI 0.99 to 5.11), p=0.0541). Sensitivity analyses of persistent IAP levels revealed that, compared with participants of the highest persistent IAP pentile (always >115 U/g stool), the rate of increase of fasting glycemia was double and the risk of developing T2DM was 1280% higher (RR: 13.80 (95% CI 1.87 to 101.3), p=0.0099) in participants of the lowest persistent IAP pentile (always <15 U/g stool). A diabetes pathogenesis model is presented.ConclusionsIAPD increases the risk of developing T2DM, and regular STAP tests would predict individual vulnerability to T2DM. Oral IAP supplementation might prevent T2DM.

Protective Properties of Intestinal Alkaline Phosphatase Supplementation on the Intestinal Barrier: Interactions and Effects

“…According to the study, healthy fecal IAP levels are generally levels that are maintained at 65.0 U/g. 155 Monitoring the levels and functionality of IAP can provide indicators of the development of T2DM and help assess treatment effectiveness and predict disease progression. However, further research is needed to validate and deepen our understanding of the relationship between IAP and T2DM.…”

“…Additionally, fecal IAP testing has been shown to indicate T2DM risk, which increases with IAP deficiency. According to the study, healthy fecal IAP levels are generally levels that are maintained at 65.0 U/g . Monitoring the levels and functionality of IAP can provide indicators of the development of T2DM and help assess treatment effectiveness and predict disease progression.…”

“…An endocrine disease study found that IAP deficiency increased the risk of diabetes. 155 IAP can play a role in ischemic heart disease by regulating intestinal barrier function to reduce LPS, thereby alleviating inflammation and insulin resistance. 11 Additionally, IAP can influence insulin sensitivity and blood glucose control by regulating the composition of the gut microbiota and the production of metabolites.…”

When AIE meets enzymes

“…Alkaline phosphatase (ALP), a common and important monophosphate hydrolase in the course of cell mineralization and osteogenic differentiation, has always been regarded as an essential biomarker for several clinical diagnostics such as liver dysfunctions, bone diseases, heart failure, and diabetes. 46,47 The analysis of ALP activity had been established based on the AIE enzyme probe with a solubility change in recent years. In 2013, Zhang et al synthesized the phosphorylated TPE fluorescent probe TPE-PA for the detection of ALP.…”

Pasture intake protects against commercial diet-induced lipopolysaccharide production facilitated by gut microbiota through activating intestinal alkaline phosphatase enzyme in meat geese

“…Furthermore, intestinal ALP promotes healthy homeostasis of gut microbiota ( 28 ) and gut barrier functions ( 29 ), which has been associated with lowering systemic inflammation in several studies of healthy adults ( 30 ) and their specific health conditions (e.g. obesity, diabetes, and cardiovascular disease) ( 31 ). The increasing evidence of the salutary functions of ALP emphasizes the significance of the naturally occurring brush border enzyme.…”