Prostaglandins are lipid mediators involved in physiological processes, such as constriction or dilation of blood vessels, but also pathophysiological processes, which include inflammation, pain and fever. They are produced by almost all cell types in the organism by activation of Prostaglandin endoperoxide synthases/Cyclooxygenases. The inducible Prostaglandin Endoperoxide Synthase 2/Cyclooxygenase 2 (PTGS2/COX2) plays an important role in pathologies associated with inflammatory signaling. The main product derived from PTGS2/COX2 expression and activation is Prostaglandin E2 (PGE2), which promotes a wide variety of tissue-specific effects, pending environmental inputs. One of the major sources of PGE2 are infiltrating inflammatory cells - the production of this molecule increases drastically in damaged tissues. Immune infiltration is a hallmark of type 1 diabetes mellitus, a multifactorial disease that leads to autoimmune-mediated pancreatic beta cell destruction. Controversial effects for the PTGS2/COX2-PGE2 signaling cascade in pancreatic islet cells subjected to diabetogenic conditions have been reported, allocating PGE2 as both, cause and consequence of inflammation. Herein, we review the main effects of this molecular pathway in a tissue-specific manner, with a special emphasis on beta cell mass protection/destruction and its potential role in the prevention or development of T1DM. We also discuss strategies to target this pathway for future therapies.

The antidiabetic action of traditional plants is mostly attributed to their antioxidant and anti-inflammatory properties. These plants are still having some secrets, making them an attractive source that allows for investigating new drugs or uncovering precise pharmacologic antidiabetic functions of their constituents. In diabetes, which is a lipid disease, long-term exposure of pancreatic islet beta cells to fatty acids (FAs) increases basal insulin release, reduces glucose-stimulated insulin secretion, causes islet beta cell inflammation, failure and apoptosis. Pancreatic islet beta cells express fatty acid binding protein 3 (FABP3) that receives long-chain FAs and traffics them throughout different cellular compartments to be metabolized and render their effects. Inhibition of this FABP3 may retard FA metabolism and protect islet beta cells. Since FAs interact with FABPs by their carboxylic group, some traditionally-known antidiabetic plants were reviewed in the present study, searching for their components that have common features of FABP ligands, namely carboxylic group and hydrophobic tail. Many of these carboxylic acids were computationally introduced into the ligand-binding pocket of FABP3 and some of them exhibited FABP3 ligand possibilities. Among others, the naturally occurring ferulic, cleomaldeic, caffeic, sinapic, hydroxycinnamic, 4-p-coumaroylquinic, quinoline-2-carboxylic, chlorogenic, 6-hydroxykynurenic, and rosmarinic acids in many plants are promising candidates for being FABP3-specific inhibitors. The study shed light on repurposing these phyto-carboxylic acids to function as FABP inhibitors. However, more in-depth biological and pharmacological studies to broaden the understanding of this function are needed.

OBJECTIVE: Isolated pancreatic islets are valuable resources for a wide range of research, including cell replacement studies and cell-based platforms for diabetes drug discovery and disease modeling. Islet isolation is a complex and stepwise procedure aiming to obtain pure, viable, and functional islets for in vitro and in vivo studies. It should be noted that differences in rodent strains, gender, weight, and density gradients may affect the isolated islet\'s properties. We evaluated the variables affecting the rat islet isolation procedure to reach the maximum islet yield and functionality, which would be critical for further studies on islet regenerative biology.
METHODS: The present experimental study compared the yield and purity of isolated islets from nondiabetic rats of two different strains. Next, islet particle number (IPN) and islet equivalent (IEQ) were compared between males and females, and the weight range that yields the highest number of islets was investigated. Moreover, the influence of three different density gradients, namely Histopaque, Pancoll, and Lymphodex, on final isolated islets purity and yield were assessed. Finally, the viability and functionality of isolated islets were measured.
RESULTS: The IEQ, IPN, and purity of isolated islets in 15 Lister hooded rats (LHRs) were significantly (P≤0.05) higher than those of the other strains. Male LHRs resulted in significantly higher IEQ compared to females (P≤0.05). Moreover, IPN and IEQ did not significantly vary among different weight groups. Also, the utilization of Histopaque and Pancoll leads to higher yield and purity. In vivo assessments of the isolated islets presented significantly reduced blood glucose percentage in the transplanted group on days 2-5 following transplantation.
CONCLUSIONS: Based on these results, an optimal protocol for isolating high-quality rat islets with a constant yield, purity, and function has been established as an essential platform for developing diabetes research.

Fibroblast growth factor 1 (FGF-1), also known as acidic fibroblast growth factor (aFGF), is a growth factor and signaling protein encoded by the Fgf1 gene. Previous studies have shown that FGF-1 may also participate in the regulation of glucose metabolism, both in healthy organisms and in pathological conditions such as diabetes. Because insulin the main regulator of glucose metabolism is secreted from pancreatic beta cells, we investigated whether FGF-1 directly affects the secretion of this hormone and regulates the metabolism of beta cells and isolated pancreatic islets. By using insulin-producing INS-1E cells and isolated pancreatic islets, we investigated the effect of FGF-1 on cell proliferation, viability, apoptosis, and insulin expression and secretion. Our study showed that FGF1 and fibroblast growth factor receptors (FgfRs: FgfR1, FgfR2, FgfR3, and FgfR4) are present on mRNA level in INS-1E cells and isolated rat pancreatic islets. We also proved that FGF1 stimulates the proliferation of INS-1E beta cells and enhances the viability of these cells and that of isolated pancreatic islet cells, and that ERK1/2 kinase is involved in the regulation of INS-1E cell proliferation. Moreover, we found that FGF1 can stimulate insulin secretion from both INS-1E cells and isolated rat pancreatic islets. Thus, the FGF1 peptide increases cell survival and decreases cell death. The obtained results indicate that FGF1 may play a role in controlling the physiology and metabolism of pancreatic beta cells as well as glycemia.

Pteronotus personatus as an insectivore bat and has a diet that consists of a high protein diet, whereas the diet of Anoura geoffroyi, a predominantly nectarivore bat, is rich in simple sugars like sucrose, glucose and fructose. Considering that diet influences the activation of different pathways, which may influence morphological adaptations in the gastrointestinal system, the aim of this study was to compare the morphology of the endocrine pancreas in P. personatus and A. geoffroyi. For this, histological, stereological and immunohistochemical methods were used. In P. personatus, the average diameter of the pancreatic islet was 40.47μm±13.94, while in A. geoffroyi was 88.16μm±36.40. The total number of pancreatic islets in P. personatus was 26150±2346 and in A. geoffroyi was 15970±1666. In P. personatus, the volume density of the pancreatic islets was 3.4%± 2.6, whereas in A. geoffroyi the volume density was 6.1%±3.7. In addition, the immunodensity of the α, β and δ cells, in P. personatus was 25.8%±11.9, 35.5%±13.5, 3.9%±0.7, respectively, and in A. geoffroyi was 33.10%±12.7, 55.08%±7.4, 6.2%±4.6, respectively. In conclusion, the results of this study indicate differences in the pancreatic weight/body, weight ratio, diameter and volume density of pancreatic islets and in immunodensity of the β and α cells between both species, which have different dietary habits.

BACKGROUND: Xenotransplantation using pig cells, tissues, or organs may be associated with the transmission of porcine microorganisms and the development of zoonoses. Among all porcine microorganisms porcine endogenous retroviruses (PERVs) represent a special risk because they are integrated in the genome of all pigs and able to infect human cells. In previous preclinical and retrospective clinical trials of xenotransplantation, no transmission of PERV was observed. The first clinical trial of (alginate-encapsulated) porcine islet cell transplantation in New Zealand, which was approved by the New Zealand Government as an open-label phase I/IIa safety/efficacy trial, offers the possibility to analyze microbiological safety in a prospective clinical study.
METHODS: Before the trial started, a multilevel testing strategy was used to screen for 26 microorganisms in donor pigs of the Auckland Island strain and the islet cell preparations used for treatment. Donor testing was performed using molecular methods including multiplex real-time PCR. Blood samples from 14 pig islet cell recipients were also investigated by molecular biological methods at weeks 1, 4, 8, 12, 24, and 52 post-transplant for the transmission of porcine microorganisms. Sera were also monitored at these time points for antibodies against PERVs.
RESULTS: Beginning in 2009, fourteen patients with severe unaware hypoglycemia were treated with one of four different dosages of alginate-encapsulated porcine islets ranging from 5000-20,000 islet equivalents delivered in a single dose. No transmission of either PERVs or other porcine microorganisms was detected by PCR and immunological methods.
CONCLUSIONS: These findings support previous results and strongly indicate the safety of xenotransplantation as performed here.

Emerging reports on the organization of the different hormone-secreting cell types (alpha, glucagon; beta, insulin; and delta, somatostatin) in human islets have emphasized the distinct differences between human and mouse islets, raising questions about the relevance of studies of mouse islets to human islet physiology. Here, we examine the differences and similarities between the architecture of human and mouse islets. We studied islets from various mouse models including ob/ob and db/db and pregnant mice. We also examined the islets of monkeys, pigs, rabbits and birds for further comparisons. Despite differences in overall body and pancreas size as well as total beta-cell mass among these species, the distribution of their islet sizes closely overlaps, except in the bird pancreas in which the delta-cell population predominates (both in singlets and clusters) along with a small number of islets. Markedly large islets (>10,000 mum(2)) were observed in human and monkey islets as well as in islets from ob/ob and pregnant mice. The fraction of alpha-, beta- and delta-cells within an islet varied between islets in all the species examined. Furthermore, there was variability in the distribution of alpha- and delta-cells within the same species. In summary, human and mouse islets share common architectural features that may reflect demand for insulin. Comparative studies of islet architecture may lead to a better understanding of islet development and function.