Origins of the short circuit current of a current mismatched multijunction photovoltaic cell considering subcell reverse breakdown.

In the photovoltaic community, short circuit current (Isc) of a current mismatched multijunction photovoltaic (MJPV) cell was usually thought to be limited by the lowest subcell photocurrent (Imin). However, under certain conditions for multijunction solar cells, Isc≠Imin was observed by researchers, while this effect has not been studied in multijunction laser power converters (MJLPCs). In this work, we provide an in-depth analysis of the formation mechanisms for the Isc of the MJPV cell by measuring I-V curves of the GaAs and InGaAs LPCs with different number of subcells and simulating the I-V curves with the reverse breakdown of each subcell considered. It is found that Isc of an N-junction PV cell can be theoretically equal to any current value within a range from a current lower than Imin to the maximum subcell photocurrent, which is up to the number of subcell current steps in the forward biased I-V curve. An MJPV cell with a constant Imin will demonstrate a higher Isc if it has more subcells, smaller subcell reverse breakdown voltage and smaller series resistance. As a result, Isc tends to be limited by the photocurrent of a subcell closer to the middle cell and is less sensitive to the optical wavelength than Imin. This should be another possible reason why the measured EQE of a multijunction LPC exhibits a wider spectrum width than the calculated Imin-based EQE, whereas this was usually attributed to the luminescent coupling effect merely.

Endoplasmic reticulum stress induced by lipopolysaccharide is involved in the association between inflammation and autophagy in INS­1 cells.

Type 2 diabetes is a chronic inflammatory disease. Autophagy, the dynamic process of lysosomal degradation of damaged organelles and proteins, may protect ß­cells from destruction by inflammation in type 2 diabetes. The present study investigated the role of autophagy, inflammation and endoplasmic reticulum (ER) stress in type 2 diabetes. INS­1 cells were incubated with lipopolysaccharide. The chemical chaperone 4­phenylbutyric acid was used to inhibit ER stress, and 3­methyadenine (3­MA) was used to inhibit autophagy. Apoptosis was detected by flow cytometry and cell proliferation using Cell Counting kit­8 solution. Light chain­3B, interleukin (IL) 1ß, caspase­1 and C/EBP homologous protein production were assessed by western blotting, and rat activating transcription factor 4 and rat binding immunoglobulin heavy chain protein gene expression were determined by real­time reverse transcription­polymerase chain reaction. The results showed that inhibiting autophagy with 3­MA unexpectedly contributed to cell death in ß­cells. This response was associated with an increase in inflammatory cytokines, including IL1ß and caspase­1. Inhibiting ER stress with 4­phenylbutyric acid led to a decrease in cell apoptosis. These results showed that autophagy may have a protective effect by reducing inflammatory cytokines in ß­cells. In addition, the inositol­requiring enzyme 1 pathway mediated the ER stress associated with autophagy and inflammatory cytokines (IL1ß and caspase­1). Therefore, inflammatory cytokines may be critical signalling nodes, which are associated with ER stress­mediated ß­cell death.

Inhibiting autophagy promotes endoplasmic reticulum stress and the ROS­induced nod­like receptor 3­dependent proinflammatory response in HepG2 cells.

Inflammation and endoplasmic reticulum (ER) stress are key contributors to insulin resistance and metabolic disease, and interleukin (IL)­1ß is involved in insulin resistance. The present study aimed to investigated the role of autophagy in LPS­induced ER stress and inflammation, which may provide evidence for controlling metabolic disease associated with inflammation. Lipopolysaccharide (LPS) induced the activation of ER stress and the nod­like receptor 3­dependent expression of IL­1ß and caspase­1, as shown by western blotting, which contributed to HepG2 cell death. This also involved the generation of mitochondrial reactive oxygen species and the autophagy signaling response, which are derived from the ER stress pathway. The percentage of apoptotic cells was measured by flow cytometry with fluorescein isothiocyanate/propidium iodide staining. Reactive oxygen species formation was detected by flow cytometry using the peroxide sensitive fluorescent probe 2',7'­dichlorofluorescin diacetate. Autophagy activation was measured by western blotting and confirmed using transmission electron microscopy. Furthermore, inhibiting autophagy promoted ER stress and the proinflammatory response in addition to cell death. These findings provide insights into the protective role of autophagy in LPS­induced cell death and ER stress, and further identified the association of autophagy, ER stress and inflammation in HepG2 cells.

Liraglutide prevents high glucose level induced insulinoma cells apoptosis by targeting autophagy.

BACKGROUND: The pathophysiology of type 2 diabetes is progressive pancreatic beta cell failure with consequential reduced insulin secretion. Glucotoxicity results in the reduction of beta cell mass in type 2 diabetes by inducing apoptosis. Autophagy is essential for the maintenance of normal islet architecture and plays a crucial role in maintaining the intracellular insulin content by accelerating the insulin degradation rate in beta cells. Recently more attention has been paid to the effect of autophagy in type 2 diabetes. The regulatory pathway of autophagy in controlling pancreatic beta cells is still not clear. The aim of our study was to evaluate whether liraglutide can inhibit apoptosis and modulate autophagy in vitro in insulinoma cells (INS-1 cells). METHODS: INS-1 cells were incubated for 24 hours in the presence or absence of high levels of glucose, liraglutide (a long-acting human glucagon-like peptide-1 analogue), or 3-methyadenine (3-MA). Cell viability was measured using the Cell Counting Kit-8 (CCK8) viability assay. Autophagy of INS-1 cells was tested by monodansylcadaverine (MDC) staining, an autophagy fluorescent compound used for the labeling of autophagic vacuoles, and by Western blotting of microtubule-associated protein I light chain 3 (LC3), a biochemical markers of autophagic initiation. RESULTS: The viability of INS-1 cells was reduced after treatment with high levels of glucose. The viability of INS-1 cells was reduced and apoptosis was increased when autophagy was inhibited. The viability of INS-1 cells was significantly increased by adding liraglutide to supplement high glucose level medium compared with the cells treated with high glucose levels alone. CONCLUSIONS: Apoptosis and autophagy were increased in rat INS-1 cells when treated with high level of glucose, and the viability of INS-1 cells was significantly reduced by inhibiting autophagy. Liraglutide protected INS-1 cells from high glucose level-induced apoptosis that is accompanied by a significant increase of autophagy, suggesting that liraglutide plays a role in beta cell apoptosis by targeting autophagy. Thus, autophagy may be a new target for the prevention or treatment of diabetes.

Autophagy regulates inflammation following oxidative injury in diabetes.

T1D (type 1 diabetes) is an autoimmune disease characterized by lymphocytic infiltration, or inflammation in pancreatic islets called 'insulitis.' Comparatively speaking, T2D (type 2 diabetes) is traditionally characterized by insulin resistance and islet ß cell dysfunction; however, a number of studies have clearly demonstrated that chronic tissue inflammation is a key contributing factor to T2D. The NLR (Nod-like receptor) family of innate immune cell sensors such as the NLRP3 inflammasome are implicated in leading to CASP1 activation and subsequent IL1B (interleukin 1, ß) and IL18 secretion in T2D. Recent developments reveal a crucial role for the autophagy pathway under conditions of oxidative stress and inflammation. Increasingly, research on autophagy has begun to focus on its role in interacting with inflammatory processes, and thereby how it potentially affects the outcome of disease progression. In this review, we explore the pathophysiological pathways associated with oxidative stress and inflammation in T2D. We also explore how autophagy influences glucose homeostasis by modulating the inflammatory response. We will provide here a perspective on the current research between autophagy, inflammation and T2D.

The role of autophagy in endoplasmic reticulum stress-induced pancreatic ß cell death.

In pancreatic ß-cells, the endoplasmic reticulum (ER) is the crucial site for insulin biosynthesis, as this is where the protein-folding machinery for secretory proteins is localized. Perturbations to ER function of the ß-cell, such as those caused by high levels of free fatty acid and insulin resistance, can lead to an imbalance in protein homeostasis and ER stress, which has been recognized as an important mechanism for type 2 diabetes. Macroautophagy (hereafter referred to as autophagy) is activated as a novel signaling pathway in response to ER stress. In this review, we outline the mechanism of ER stress-mediated ß-cell death and focus on the role of autophagy in ameliorating ER stress. The development of drugs to take advantage of the potential protective effect of autophagy in ER stress, such as glucagon like peptide-1, will be a promising avenue of investigation.

Effect of simvastatin on expression of transforming growth factor-ß and collagen type IV in rat mesangial cells.

OBJECTIVE: Diabetic nephropathy is characterized by the accumulation of extracellular matrix in the glomerular mesangium as a result of an imbalance between matrix synthesis and degradation. Since simvastatin has been proposed to decrease renal interstitial fibrosis, we hypothesized that the protective effect of statins was related to the expression of transforming growth factor-ß (TGF-ß) and type IV collagen (Col IV). METHODS: Cultured rat mesangial cells (RMC) were exposed to high glucose (HG), advanced glycosylation end products (AGE) or H(2)O(2) in the absence and presence of simvastatin. Expression of TGF-ß and Col IV was determined by Western blotting. RESULTS: Coincubation of RMC with HG, AGE or H(2)O(2) resulted in a significant increase of the expression of TGF-ß and Col IV (p < 0.05). Simvastatin significantly inhibited HG-, AGE- or H(2)O(2)-induced expression of TGF-ß and Col IV (p < 0.05). Moreover, simvastatin also inhibited HG-, AGE- and H(2)O(2)-induced activation of p38 mitogen-activated protein kinase, which indicated that the preventive effect of simvastatin on TGF-ß and Col IV may be associated with p38. CONCLUSION: These findings suggest that simvastatin can reduce HG-, AGE- and H(2)O(2)-induced expression of TGF-ß and Col IV by inhibition of the p38 pathway.

The double-edged effect of autophagy in pancreatic beta cells and diabetes.

Autophagy is an intracellular catabolic system, which enables cells to capture cytoplasmic components for degradation within lysosomes. Autophagy is involved in development, differentiation and tissue remodeling in various organisms, and is also implicated in certain diseases. Recent studies demonstrate that autophagy is necessary to maintain architecture and function of pancreatic beta cells. Altered autophagy is also involved in pancreatic beta cell death. Whether autophagy plays a protective or harmful role in diabetes is still not clear. In this review, we will summarize the current knowledge about the role of autophagy in pancreatic beta cell and diabetes.