Involvement of stanniocalcins in the deregulation of glycaemia in obese mice and type 2 diabetic patients

Abstract

Stanniocalcins are expressed in the pancreas tissue, and it was suggested a direct correlation between circulating insulin and STC2 concentrations in human. Here, we show a significant correlation between STC1 and both glycaemia and glycosylated haemoglobin among DM2 patients, while DM2 patients who present the greatest glycosylated haemoglobin values exhibited the lowest STC2 expression. However, treatment of patients with antiglycaemic drugs does not significantly modify the expression of both STCs. On the other hand, STC2‐/‐ mice that exhibited neonatal and adult overweight further presented deregulated glycaemia when they were feed with a hypercaloric diet (breeding pellet, BP). This alteration is more evident at the early stages of the animal life. Deregulated glycaemia in these mice was confirmed using glucose oral test. In addition, STC2‐/‐ mice present enhanced pancreas size; thus, the histological analysis reveals that WT mice respond to BP diet by increasing the size of the pancreatic islets through inducing cell division, and STC2‐/‐ mice lack this compensatory mechanism. Contrary, BP fed STC2‐/‐ mice show enhanced number of islets but of similar size than those fed with regular pellet. Histopathological analysis demonstrates tissue structure disruption and erythrocytes infiltrations in STC2‐/‐ mice, possibly due to the stress evoked by the BP diet. Finally, enhanced glucagon immunostaining was observed in the islet of STC2‐/‐ mice, and the glucagon ELISA assay confirmed the increase in the circulating glucagon. Summarizing, we present evidence of the role of STCs, mainly STC2, as a possible early marker during development of diabetes mellitus.

Stanniocalcin 2 Regulates Non-capacitative Ca2+ Entry and Aggregation in Mouse Platelets

“…We have recently suggested that STC2 might be involved in the pathophysiology of type 2 diabetes mellitus, where STC2 is downregulated (Lopez et al, 2017 ). We have previously reported that platelets from patients with type 2 diabetes mellitus exhibit both hyperactivity and hyperaggregability (Saavedra et al, 2004 ; Redondo et al, 2005 ; Lopez et al, 2013b ).…”

“…In mouse embryonic fibroblasts STC2 overexpression results in reduced SOCE probably mediated by interaction with STIM1 (Zeiger et al, 2011 ), which strongly suggests a possible role for STC2 in the regulation of SOCE. We have recently reported that STC2 is expressed in human and mouse platelets (Lopez et al, 2017 ). Here we provide for the first time evidence for a role of STC2 in the regulation of Ca 2+ entry and aggregation in mouse platelets.…”

New Insights Into Physiological and Pathophysiological Functions of Stanniocalcin 2

“…Similarly, Zhao et al showed that STC2 ameliorated hepatosteatosis and hypertriglyceridemia in obese mice through the activation of Signal transducer and activator of transcription 3 (STAT3) signaling pathway (10). STC2 has also been involved in deregulation of glycaemia in obese mice as well as in type 2 diabetes mellitus patients (8). Additionally, it was speculated that STC2 might play role in glucose uptake and metabolism, glycogen storage and triacylglycerol synthesis in both brown and white adipose tissues (44,63).…”

“…The stanniocalcin-historically known as hypocalcin, teleocalcin, or parathyrin-is a widely-expressed hormone that is speculated to function in an autocrine and/or paracrine manner (1,2). Various studies have indicated the possible involvement of two mammalian stanniocalcins, namely stanniocalcin 1 and 2 (STC1 and 2), in diverse biological processes including calcium regulation, cell proliferation and apoptosis, inflammation, Endoplasmic Reticulum (ER)/oxidative stress, metabolism, and cancer (3)(4)(5)(6)(7)(8)(9)(10). However, precise physiological functions and signaling pathways in which stanniocalcins are involved remain to be elucidated.…”

Peer Review #2 of "Comprehensive analysis of long non-coding RNAs and mRNAs in skeletal muscle of diabetic Goto-Kakizaki rats during the early stage of type 2 diabetes (v0.1)"

“…As the expression of Ephx2 was lower in skeletal muscle than in kidney and liver, the reduced Ephx2 might have a weaker effect on glucose clearance in skeletal muscle of GK rats at the age of 3 and 4 weeks. Whole-body Stc2 and Cep19 knockout mice displayed significantly increased circulating glucose concentration (Lopez et al 2018), and markedly impaired glucose tolerance and insulin resistant (Shalata et al 2013), respectively. It has been explored that overexpressed Il15 transgenic mice showed better glucose tolerance compared to wild-type mice, and Glut4 translocation was promoted in skeletal muscle by AMP-Activated protein kinase pathway (Fujimoto et al 2019).…”