Existence of Islet Regenerating Factors within the Pancreas

Reduction in the functional mass of β-cells is a common denominator in most forms of diabetes. Since the replicative potential of β-cells is limited, the search for factors that trigger islet neogenesis becomes imperative. Here we tested the hypothesis that regenerating factors for the pancreas are either secreted by or present within the pancreatic milieu itself. For this purpose, we intraperitoneally injected pancreatic cell culture supernatant (PCCS), from normal pancreas, into streptozotocin(STZ)-induced diabetic mice for 15 consecutive days. The PCCS-treated mice showed sustained reversal in 77.77% of experimental diabetic mice as evidenced by restoration of normoglycemia, increase in serum insulin levels and occurrence of neo islets in histopathological studies during a two month follow up, as opposed to the control diabetic mice which remained hyperglycemic throughout. In order to examine the potential of PCCS to bring about the regeneration of islets, we treated intra-islet precursor cells with PCCS in vitro, which led to the neogenesis of islets as evidenced by dithiozone and insulin immunostaining. These findings substantiate our hypothesis and make the search for regenerative factors converge towards the pancreas and its immediate surroundings. Such regenerative approaches, in combination with other therapeutic strategies to promote islet neogenesis may, in future, provide a cure and/or better means for the control and management of diabetes

Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: a prophylactic and protective role

Pancreatic islet cell death is the cause of deficient insulin production in diabetes mellitus. Approaches towards prevention of cell death are of prophylactic importance in control and management of hyperglycemia. Generation of oxidative stress is implicated in streptozotocin, a beta cell specific toxin-induced islet cell death. In this context, antioxidants raise an interest for therapeutic purposes. Curcumin, a common dietary spice is a well known antioxidant and hence we investigated its effect on streptozotocin-induced islet damage in vitro. Isolated islets from C57/BL6J mice were incubated with curcumin for 24 h and later exposed to streptozotocin for 8 h. The effect of streptozotocin exposure to islets was determined with respect to islet viability and functionality, cellular reactive oxygen species concentrations and levels of activated poly (ADP-ribose) polymerase-1. Cellular antioxidant potential (Cu/Zn superoxide dismutase) and advanced glycation end-product related damage was assessed to determine the metabolic status of treated and untreated islets. Islet viability and secreted insulin in curcumin pretreated islets were significantly higher than islets exposed to streptozotocin alone. Curcumin retarded generation of islet reactive oxygen species along with inhibition of Poly ADP-ribose polymerase-1 activation. Although curcumin did not cause overexpression of Cu/Zn superoxide dismutase, it prevented reduction in levels of cellular free radical scavenging enzymes. Our data shows that curcumin protects islets against streptozotocin-induced oxidative stress by scavenging free radicals. We show here for the first time, that prophylactic use of curcumin may effectively rescue islets from damage without affecting the normal function of these cellular structures

Approaches Towards Endogenous Pancreatic Regeneration

The phenomenon of pancreatic regeneration in mammals has been well documented. It has been shown that pancreatic tissue is able to regenerate in several species of mammal after surgical insult. This tissue is also known to have the potential to maintain or increase its β-cell mass in response to metabolic demands during pregnancy and obesity. Since deficiency in β-cell mass is the hallmark of most forms of diabetes, it is worthwhile understanding pancreatic regeneration in the context of this disease. With this view in mind, this article aims to discuss the potential use in clinical strategies of knowledge that we obtained from studies carried out in animal models of diabetes. Approaches to achieve this goal involve the use of biomolecules, adult stem cells and gene therapy. Various molecules, such as glucagon-like peptide-1, β-cellulin, nicotinamide, gastrin, epidermal growth factor-1 and thyroid hormone, play major roles in the initiation of endogenous islet regeneration in diabetes. The most accepted hypothesis is that these molecules stimulate islet precursor cells to undergo neogenesis or to induce replication of existing β-cells, emphasizing the importance of pancreas-resident stem/progenitor cells in islet regeneration. Moreover, the potential of adult stem cell population from bone marrow, umbilical cord blood, liver, spleen, or amniotic membrane, is also discussed with regard to their potential to induce pancreatic regeneration

DESIGNING OF TEMPERATURE & HUMIDITY MONITORING EMBEDDED SYSTEMS

The places such as weather forecasting system, nuclear radiation measurement, greenhouses, agro-automation systems require real-time monitoring of environmental parameters like temperature and humidity. So a low-cost, low-power temperature and humidity sensor interfacing with embedded systems using PIC microcontroller and PLC is designed. The paper is analyzing the operating mechanism of DHT11 temperature and humidity combined sensor; where it features temperature and humidity sensor complex with calibrated digital signal output. The DHT11 sensor interfacing with controller is programmed, then the temperature and humidity acquisition program porting to embedded platform. Meanwhile, the data through human machine interface is intuitive feedback to the user

Designing Of Temperature & Humidity Monitoring Embedded Systems

The places such as weather forecasting system, nuclear radiation measurement, greenhouses, agro-automation systems require real-time monitoring of environmental parameters like temperature and humidity. So a low-cost, low-power temperature and humidity sensor interfacing with embedded systems using PIC microcontroller and PLC is designed. The paper is analyzing the operating mechanism of DHT11 temperature and humidity combined sensor; where it features temperature and humidity sensor complex with calibrated digital signal output. The DHT11 sensor interfacing with controller is programmed, then the temperature and humidity acquisition program porting to embedded platform. Meanwhile, the data through human machine interface is intuitive feedback to the user

Enhanced Growth of Endothelial Precursor Cells on PCG-Matrix Facilitates Accelerated, Fibrosis-Free, Wound Healing: A Diabetic Mouse Model

<div><p>Diabetes mellitus (DM)-induced endothelial progenitor cell (EPC) dysfunction causes impaired wound healing, which can be rescued by delivery of large numbers of ‘normal’ EPCs onto such wounds. The principal challenges herein are (a) the high number of EPCs required and (b) their sustained delivery onto the wounds. Most of the currently available scaffolds either serve as passive devices for cellular delivery or allow adherence and proliferation, but not both. This clearly indicates that matrices possessing both attributes are ‘the need of the day’ for efficient healing of diabetic wounds. Therefore, we developed a system that not only allows selective enrichment and expansion of EPCs, but also efficiently delivers them onto the wounds. Murine bone marrow-derived mononuclear cells (MNCs) were seeded onto a PolyCaprolactone-Gelatin (PCG) nano-fiber matrix that offers a combined advantage of strength, biocompatibility wettability; and cultured them in EGM2 to allow EPC growth. The efficacy of the PCG matrix in supporting the EPC growth and delivery was assessed by various in vitro parameters. Its efficacy in diabetic wound healing was assessed by a topical application of the PCG-EPCs onto diabetic wounds. The PCG matrix promoted a high-level attachment of EPCs and enhanced their growth, colony formation, and proliferation without compromising their viability as compared to Poly L-lactic acid (PLLA) and Vitronectin (VN), the matrix and non-matrix controls respectively. The PCG-matrix also allowed a sustained chemotactic migration of EPCs in vitro. The matrix-effected sustained delivery of EPCs onto the diabetic wounds resulted in an enhanced fibrosis-free wound healing as compared to the controls. Our data, thus, highlight the novel therapeutic potential of PCG-EPCs as a combined ‘growth and delivery system’ to achieve an accelerated fibrosis-free healing of dermal lesions, including diabetic wounds.</p></div

PCG-EPC-treated wound healing mimics normal wound healing process.

<p>Histopathological analyses of wound healing process from d 2 to 10. Non-diabetic controls (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069960#pone-0069960-g007" target="_blank">Figure 7</a>; images ‘a’ to ‘e’), untreated diabetic controls (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069960#pone-0069960-g007" target="_blank">Figure 7</a>; images ‘f’ to ‘j’), PLLA-EPC-treated diabetic wounds (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069960#pone-0069960-g007" target="_blank">Figure 7</a>; images ‘k’ to ‘o’) and PCG-EPC-treated diabetic wound (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069960#pone-0069960-g007" target="_blank">Figure 7</a>; images ‘p’ to ‘t’) (10× magnification) show that PCG-EPC-treated wounds mimic normal wound healing process. All data are representative of at least 3 independent experiments with at least 3 mice per time point.</p

% viability of migrated cells at 24, 48 and 72h.

<p>PCG-EPCs exhibited higher viability post-migration as compared to VN and PLLA-EPCs. Although a progressive decrease in % cellular viability was observed over 24, 48 and 72 h time points in all groups, PCG-EPCs show significantly higher maintenance of cellular viability as compared to its PLLA and VN-EPC counterparts at all time points (*<i>p</i><0.001). Results are represented as mean ± SD of at least 3 independent experiments (n = 4/5).</p

Chemotactic migration of EPCs grown on various matrices.

<p>Comparative EPC migration towards VEGF (50 ng/ml) in vitro at 24, 48 and 72 h from VN, PLLA and PCG matrix is graphically illustrated. Data are represented as mean of at least 3 independent experiments (n = 3) ± SD. Each experiment had at least 4 wells per group. EPCs from both electro-spun matrices consistently exhibited a slower cellular migration compared to those from VN at all time points (*p<0.001).</p