Arp2/3 nucleates F-actin coating of fusing insulin granules in pancreatic β cells to control insulin secretion

F-actin dynamics are known to control insulin secretion, but the point of intersection with the stimulus-secretion cascade is unknown. Here, using multiphoton imaging of β cells isolated from Lifeact-GFP transgenic mice, we show that glucose stimulation does not cause global changes in subcortical F-actin. Instead, we observe spatially discrete and transient F-actin changes around each fusing granule. This F-actin remodelling is dependent on actin nucleation and is observed for granule fusion induced by either glucose or high potassium stimulation. Using GFP-labelled proteins, we identify local enrichment of Arp3, dynamin 2 and clathrin, all occurring after granule fusion, suggesting early recruitment of an endocytic complex to the fusing granules. Block of Arp2/3 activity with drugs or shRNA inhibits F-actin coating, traps granules at the cell membrane and reduces insulin secretion. Block of formin-mediated actin nucleation also blocks F-actin coating, but has no effect on insulin secretion. We conclude that local Arp2/3-dependent actin nucleation at the sites of granule fusion plays an important role in post-fusion granule dynamics and in the regulation of insulin secretion

TRAIL-Expressing Monocyte/Macrophages Are Critical for Reducing Inflammation and Atherosclerosis.

Circulating tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) levels are reduced in patients with cardiovascular disease, and TRAIL gene deletion in mice exacerbates atherosclerosis and inflammation. How TRAIL protects against atherosclerosis and why levels are reduced in disease is unknown. Here, multiple strategies were used to identify the protective source of TRAIL and its mechanism(s) of action. Samples from patients with coronary artery disease and bone-marrow transplantation experiments in mice lacking TRAIL revealed monocytes/macrophages as the main protective source. Accordingly, deletion of TRAIL caused a more inflammatory macrophage with reduced migration, displaying impaired reverse cholesterol efflux and efferocytosis. Furthermore, interleukin (IL)-18, commonly increased in plasma of patients with cardiovascular disease, negatively regulated TRAIL transcription and gene expression, revealing an IL-18-TRAIL axis. These findings demonstrate that TRAIL is protective of atherosclerosis by modulating monocyte/macrophage phenotype and function. Manipulating TRAIL levels in these cells highlights a different therapeutic avenue in the treatment of cardiovascular disease

Islet Biology and Metabolism

This Special Issue, Islet Biology and Metabolism, was intended as a collection of studies highlighting the importance of the pancreatic islet—in both form and function—to our growing understanding of metabolic physiology and disease [...

Effects of dietary inclusion of sugarcane (saccurum officinarum) filter cake on the performances of broiler chickens

AbstractThis study evaluated the feed value of sugarcane filter cake (SFC) for broilers. A total of 336 one-day-old Cobb500 were randomly allotted to seven treatments (T) with three replications. A diet without SFC (T0, control) was formulated for the starter (1–14 days), grower (15–28 days) and finisher (29–49 days) phases. The test diets contained sun-dried SFC at two levels (5% and 10%) and varied with feeding periods [(5%SFC (T1)- and 10%SFC-based diets (T2) for the entire period, 5%SFC (T3)- and 10%SFC-based diets (T4) for grower to finisher phases and 5%SFC (T5)- and 10%SFC-based diets (T6) for finisher phase]. Feed intake (FI), final body weight (FBW), total body weight gain (TBWG) and feed conversion ratios (FCR) were not affected (P > 0.05) at the starter phase. However, FI and ADG on 10%SFC diets were reduced (P  0.05) were observed for the finisher and entire periods on 5%SFC-based diets. The overall FI, ADG and FCR did not vary among treatments (P > 0.05) however, TBWG was highest in T5 and T6. The overall feed consumption ranged from 3.86–4.26 kg/bird (P > 0.05). Treatments did not differ in dressed and eviscerated carcasses, cut parts, visceral organs and meat-to-bone ratios (P > 0.05). The 5%SFC- and 10%SFC-based diets resulted in higher net income. In conclusion, up to 10%SFC inclusion in the broiler diet for the whole period or at the finisher phase increases performances and economic benefit

Isolation and Proteomics of the Insulin Secretory Granule

Insulin, a vital hormone for glucose homeostasis is produced by pancreatic beta-cells and when secreted, stimulates the uptake and storage of glucose from the blood. In the pancreas, insulin is stored in vesicles termed insulin secretory granules (ISGs). In Type 2 diabetes (T2D), defects in insulin action results in peripheral insulin resistance and beta-cell compensation, ultimately leading to dysfunctional ISG production and secretion. ISGs are functionally dynamic and many proteins present either on the membrane or in the lumen of the ISG may modulate and affect different stages of ISG trafficking and secretion. Previously, studies have identified few ISG proteins and more recently, proteomics analyses of purified ISGs have uncovered potential novel ISG proteins. This review summarizes the proteins identified in the current ISG proteomes from rat insulinoma INS-1 and INS-1E cell lines. Here, we also discuss techniques of ISG isolation and purification, its challenges and potential future directions

Inside the Insulin Secretory Granule

The pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse with the plasma membrane upon cellular stimulation to release insulin. Insulin is synthesized in the endoplasmic reticulum (ER) as a biologically inactive precursor, proinsulin, along with several other proteins that will also become members of the insulin SG. Their coordinated synthesis enables synchronized transit through the ER and Golgi apparatus for congregation at the trans-Golgi network, the initiating site of SG biogenesis. Here, proinsulin and its constituents enter the SG where conditions are optimized for proinsulin processing into insulin and subsequent insulin storage. A healthy β-cell is continually generating SGs to supply insulin in vast excess to what is secreted. Conversely, in type 2 diabetes (T2D), the inability of failing β-cells to secrete may be due to the limited biosynthesis of new insulin. Factors that drive the formation and maturation of SGs and thus the production of insulin are therefore critical for systemic glucose control. Here, we detail the formative hours of the insulin SG from the luminal perspective. We do this by mapping the journey of individual members of the SG as they contribute to its genesis

Factors associated with low fifth minute Apgar score among newborns delivered at public health facilities of Dilla town, Southern Ethiopia, 2022

Objective: The aim of this study is to identify the associated factors of low fifth minute Apgar scores among newborns in Dilla town public health facilities, southern Ethiopia. Methods: An institution-based case-control study was conducted in Dilla town public health facilities, Southern Ethiopia. The case and control groups were newborns with fifth minute Apgar score of < 7 and ≥ 7, respectively. The study included 534 participants (178 cases and 356 controls). Data were collected through face-to-face interviews and record reviews. Consecutive and systematic random sampling was used to recruit cases and controls, respectively. Bivariate and multivariate analyses were performed. The degree of association between independent and dependent variables was assessed using adjusted odds ratios (ORs) with 95 % confidence intervals (CIs). Finally, variables with a p-value of < 0.05, were consider that had statistically significant. Results: In this study, No antenatal care follow-up [AOR = 1.74, 95 % CI: (1.12, 2.69)], instrumental mode of delivery [AOR = 2.11, 95 % CI: (1.25, 3.56)], non-vertex presentation [AOR = 6.54, 95 % CI: (2.92, 14.65)], prolonged second stage of labor [AOR = 5.63, 95 % CI: (2.45, 12.95)], and gestational hypertension [AOR = 0.45, 95 % CI: (0.22, 0.86)] were significantly associated with a low fifth minute Apgar score. Conclusions: This study found that no antenatal care follow-up, instrumental mode of delivery, pregnancy-induced hypertension, prolonged second stage of labor, and non-vertex presentation were all independently associated with low fifth-minute Apgar scores. These findings suggest the need for improved maternal and neonatal care during pregnancy, delivery, and the postpartum period to reduce the risk of low Apgar scores and to improve newborn outcomes