Pdx1 AND Beta cells

Bone marrow-derived stem cells are self-renewing and multipotent adult stem cells that differentiate into several types of cells. Here, we investigated a unique combination of 4 differentiation-inducing factors (DIFs), including putrescine (Put), glucosamine (GlcN), nicotinamide, and BP-1-102, to develop a differentiation method for inducing mature insulin-producing cells (IPCs) and apply this method to bone marrow mononucleated cells (BMNCs) isolated from mice. BMNCs, primed with the 4 soluble DIFs, were differentiated into functional IPCs...

Pancreatic beta cell function is an important component of glucose homeostasis. Here, we investigated the function of PIMT (PRIP-interacting protein with methyl transferase domain), a transcriptional co-activator binding protein, in the pancreatic beta cells. We observed that the protein levels of PIMT, along with key beta cell markers such as PDX1 (pancreatic and duodenal homeobox 1) and MafA (MAF bZIP transcription factor A), were reduced in the beta cells exposed to hyperglycemic and hyperlipidemic conditions...

Stomach stem cells are accessible by biopsy and propagate robustly in culture, offering an invaluable resource for autologous cell therapies. Here we describe a detailed protocol to isolate, expand, engineer and differentiate human gastric stem cells (hGSCs) into pancreatic islet-like organoids containing abundant gastric insulin-secreting (GINS) cells that resemble beta-cells in molecular hallmarks and function. Sequential activation of the inducing factors NGN3 and PDX1-MAFA led hGSCs onto a novel differentiation path, including endocrine progenitor and GINS precursor, before adopting beta-cell identity, at efficiencies close to 70%...

Gymnema sylvestre is traditionally used as an herbal remedy for diabetes. The effect of Gymnema sylvestre supplementation on beta cell and hepatic activity was explored in an alloxan-induced hyperglycemic adult rat. Animals were made hyperglycemic via a single inj. (i.p) of Alloxan. Gymnema sylvestre was supplemented in diet @250 mg/kg and 500 mg/kg b.w. Animals were sacrificed, and blood and tissues (pancreas and liver) were collected for biochemical, expression, and histological analysis. Gymnema sylvestre significantly reduced blood glucose levels with a subsequent increase in plasma insulin levels in a dosage-dependent manner...

Beta-cell dysfunction is a hallmark of disease progression in patients with diabetes. Research have been focused on maintaining and restoring beta-cell function during diabetes development. The aims of this study were to explore the expression of C-type lectin domain containing 11A (CLEC11A), a secreted sulfated glycoprotein, in human islets, and to evaluate the effects of CLEC11A on beta-cell function and proliferation in vitro. To test these hypotheses, human islets and human EndoC-βH1 cell line were used in this study...

BACKGROUND: Maintaining functional beta cell mass (BCM) to meet glycemic demands is essential to preventing or reversing the progression of diabetes. Yet the mechanisms that establish and regulate endocrine cell fate are incompletely understood. We sought to determine the impact of deletion of mitogen-inducible gene 6 ( Mig6 ), a negative feedback inhibitor of epidermal growth factor receptor (EGFR) signaling, on mouse endocrine cell fate. The extent to which loss of Mig6 might protect against loss of functional BCM in a multiple very low dose (MVLD) STZ-induced model of diabetes was also determined...

Diabetes mellitus is a worldwide problem characterized by hyperglycemia as well as the damage of the microscopic structure of the beta cells of Langerhans pancreatic islets. In the present study, the histological, immunohistochemical, morphometric, and biochemical alterations to pancreatic beta cells in streptozocin (STZ)-induced diabetes were assessed in rats treated with curcumin (CU) (100 mg/kg/day) or nano-curcumin (nCU) (100 mg/kg/day) for 1 month. Twenty-four adult male Wistar albino rats were distributed into four groups: the nondiabetic control group, the diabetic untreated group, and two diabetic groups treated with CU or nCUR, respectively...

Progenitor cells capable of self-renewal and differentiation in the adult human pancreas are an under-explored resource for regenerative medicine. Using micro-manipulation and three-dimensional colony assays we identify cells within the adult human exocrine pancreas that resemble progenitor cells. Exocrine tissues were dissociated into single cells and plated into a colony assay containing methylcellulose and 5% Matrigel. A subpopulation of ductal cells formed colonies containing differentiated ductal, acinar, and endocrine lineage cells, and expanded up to 300-fold with a ROCK inhibitor...

Insulinomas are rare functional pancreatic neuroendocrine tumors. While most insulinomas are indolent and cured after surgery, 10-15% of cases show aggressive or malignant tumor behavior and metastasize locally or to distant organs. Patients with metastatic insulinoma survive significantly shorter. Recognizing aggressive insulinomas can help to predict prognosis, guide therapy and determine follow-up intensity after surgery. This review offers a summary of the literature on the significant clinical, pathological, genetic and epigenetic differences between indolent and aggressive insulinomas...

Abnormalities that characterize the pathophysiology of type 2 diabetes (T2D) include deficiencies of β-cells and the expansion of α-cells in pancreatic islets, manifested by lower insulin release and glucagon oversecretion. The molecular mechanisms that determine intra-islet interactions between pancreatic α- and β-cells are still not fully understood. The present study showed that stearoyl-coenzyme A (CoA) desaturase 1 (SCD1), an enzyme that is implicated in fatty acid metabolism, serves as a checkpoint in the control of endocrine cell equilibrium in pancreatic islets...

BACKGROUND: Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease characterized by the irreversible destruction of insulin-producing β-cells in pancreatic islets. Helper and cytotoxic T-cells and cytokine production, which is impaired by this process, take a synergetic role in β-cell destruction, and hyperglycemia develops due to insulin deficiency in the body. Mesenchymal stem cells (MSCs) appear like an excellent therapeutic tool for autoimmune diseases with pluripotent, regenerative, and immunosuppressive properties...

Introduction: Measurement of pancreatic beta cell mass in animal models is a common assay in diabetes researches. Novel whole-organ clearance methods in conjunction with transgenic mouse models hold tremendous promise to improve beta cell mass measurement methods. Here, we proposed a refined method to estimate the beta cell mass using a new transgenic Tg( Pdx1-GFP ) mouse model and a recently developed free-of-acrylamide clearing tissue (FACT) protocol. Methods: First, we generated and evaluated a Tg( Pdx1-GFP ) transgenic mouse model...

Single-cell RNA sequencing has paved the way for delineating the pancreatic islet cell atlas and identifying hallmarks of diabetes. However, pathological alterations of type 2 diabetes (T2D) remain unclear. We isolated pancreatic islets from control and T2D mice for single-cell RNA sequencing (scRNA-seq) and retrieved multiple datasets from the open databases. The complete islet cell landscape and robust marker genes and transcription factors of each endocrine cell type were identified. GLRA1 was restricted to beta cells, and beta cells exhibited obvious heterogeneity...

The beta-cell identity gene, pancreatic duodenal homeobox 1 ( Pdx1 ), plays critical roles in many aspects of the life of beta-cells including differentiation, maturation, function, survival and proliferation. High levels of reactive oxygen species (ROS) are extremely toxic to cells and especially to beta-cells due to their relatively low expression of antioxidant enzymes. One of the major mechanisms for beta-cell dysfunction in type-2 diabetes results from oxidative stress-dependent inhibition of PDX1 levels and function...

Various studies have suggested a link between vitamin A (VA), all- trans -retinol, and type 2 diabetes (T2D). However, the functional role/expression of vitamin A receptors ( Rarα , β, and γ ) in pancreatic β-cells is not clear yet. Accordingly, we performed a series of bioinformatics, molecular and functional experiments in human islet and INS-1 cells to evaluate the role of Rarβ on insulin secretion and pancreatic β-cell function. Microarray and RNA-sequencing (RAN-seq) expression analysis showed that RARα , β, and γ are expressed in human pancreatic islets...

<strong>Objective:</strong> Insulin insufficiency due to the reduced pancreatic beta cell number is the hallmark of diabetes, resulting in<br />an intense focus on the development of beta-cell replacement options. One approach to overcome the problem is to<br />search for alternative sources to induce insulin-producing cells (IPCs), the advent of mesenchymal stem cells (MSCs)<br />holds great promise for producing ample IPCs. Encapsulate the MSCs with alginate improved anti-inflammatory effects<br />of MSC treatment...

Insulin expression is primarily restricted to the pancreatic β cells, which are physically or functionally depleted in diabetes. Identifying targetable pathways repressing insulin in non-β cells, particularly in the developmentally related glucagon-secreting α cells, is an important aim of regenerative medicine. Here, we perform an RNA interference screen in a murine α cell line to identify silencers of insulin expression. We discover that knockdown of the splicing factor Smndc1 triggers a global repression of α cell gene-expression programs in favor of increased β cell markers...

Thiosulfate sulfurtransferase (TST, EC 2.8.1.1), also known as Rhodanese, was initially discovered as a cyanide detoxification enzyme. However, it was recently also found to be a genetic predictor of resistance to obesity-related type 2 diabetes. Diabetes type 2 is characterized by progressive loss of adequate β-cell insulin secretion and onset of insulin resistance with increased insulin demand, which contributes to the development of hyperglycemia. Diabetic complications have been replicated in adult hyperglycemic zebrafish, including retinopathy, nephropathy, impaired wound healing, metabolic memory, and sensory axonal degeneration...

AIMS/HYPOTHESIS: The general population is ageing, involving an enhanced incidence of chronic diseases such as type 2 diabetes. With ageing, DNA methylation of FHL2 increases, as well as expression of the four and a half LIM domains 2 (FHL2) protein in human pancreatic islets. We hypothesised that FHL2 is actively involved in glucose metabolism. METHODS: Publicly available microarray datasets from human pancreatic islets were analysed for FHL2 expression. In FHL2-deficient mice, we studied glucose clearance and insulin secretion...

In the setting of obesity and insulin resistance, glycemia is controlled in part by β-cell compensation and subsequent hyperinsulinemia. Weight loss improves glycemia and decreases hyperinsulinemia, whereas weight cycling worsens glycemic control. The mechanisms responsible for weight cycling-induced deterioration in glucose homeostasis are poorly understood. Thus, we aimed to pinpoint the main regulatory junctions at which weight cycling alters glucose homeostasis in mice. Using in vivo and ex vivo procedures we show that despite having worsened glucose tolerance, weight-cycled mice do not manifest impaired whole-body insulin action...