Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells

Abstract

Background. Type 2 diabetes mellitus is a serious public health problem worldwide. Accumulating evidence has shown that β-cell dysfunction is an important mechanism underlying diabetes mellitus. e changes in the physiological state of islet stellate cells (ISCs) and the effects of these cells on β cell function play an important role in the development of diabetes. is study aimed at elucidating the mechanism by which ISCs regulate insulin secretion from Min6 cells via the Wnt5a protein. Methods. Glucosestimulated insulin secretion (GSIS) from Min6 cells was examined by estimating the insulin levels in response to high glucose challenge after culture with ISC supernatant or exogenous Wnt5a. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to observe changes in the β-catenin, receptor tyrosine kinase-like orphan receptor 2 (Ror2), Ca (2+)/calmodulin (CaM)-dependent protein kinase II (CamKII), forkhead box O1 (FoxO1), pancreatic and duodenal homeobox 1 (PDX1), glucose transporter 2 (Glut2), insulin, and Cask mRNA and protein levels in the Wnt and insulin secretory pathways. Flow cytometry was used to confirm the intracellular Ca 2+ concentration in Min6 cells. Results. We observed a significant increase in insulin secretion from Min6 cells cocultured in vitro with supernatant from db/m mouse ISCs compared to that from Min6 cells cocultured with supernatant from db/db mouse ISCs; e intracellular Ca 2+ concentration in Min6 cells increased in cultured in vitro with supernatant from db/m mouse ISCs and exogenous Wnt5a compared to that from control Min6 cells. Culture of Min6 cells with exogenous Wnt5a caused a significant increase in pCamKII, pFoxO1, PDX-1, and Glut2 levels compared to those in Min6 cells cultured alone; this treatment further decreased Ror2 and Cask expression but did not affect β-catenin expression. Conclusion. ISCs regulate insulin secretion from Min6 cells through the Wnt5a protein-induced Wntcalcium and FoxO1-PDX1-GLUT2-insulin signalling cascades.

Ginseng Pectin WGPA Alleviates Exercise-Induced Fatigue by Enhancing Gluconeogenesis

“…Meanwhile, the level of insulin, but not glucagon, dropped in WGPA-treated mice (Figures 1(i) and 1(k)). In line with this observation, the presence of WGPA downregulated the level of insulin secreted by murine pancreatic β-cell, Min6 (Figure 1(j)), which is a classic cell model widely used for evaluating insulin secretion and function in vitro [20,21,[27][28][29][30].…”

A single-cell human islet interactome atlas identifies disrupted autocrine and paracrine communications in type 2 diabetes

“…On the other side of the spectrum, alpha cells showed a unique pattern of interactions compared with other endocrine and non-endocrine cell types and, interestingly, appear as the cell type with the highest number of interactions. Indeed, it was described that pancreatic islets can contain specific sub-populations of non-endocrine cells, including the so-called islet stellate cells ( 24 ), that can interact with endocrine cells and affect their function. Increasing evidence associates stellate cells with islet fibrosis ( 29–32 ), pancreatitis and T2D progression ( 33 ).…”

The biological functions and pathological mechanisms of CASK in various diseases

“…β-cell dysfunction determines the development and progression of type 2 diabetes (T2DM) [ [45] , [46] , [47] , [48] ]. Extensive studies have examined the physiological mechanisms of biogenesis and sorting and exocytosis of insulin granules; however, the precise mechanisms that control these processes and their disorders in the development of diabetes remain an important research field.…”