β-Cell adaptation to maternal insulin resistance of pregnancy involves upregulation of β-cell mass and function, a process we previously showed depends on prolactin receptor (PRLR) signaling. Emerging evidence in humans suggests that prolactin signaling may also influence β-cell function beyond pregnancy. This study aims to investigate how postpregnancy metabolic stress-specifically the combined effects of prior pregnancy followed by high-fat diet (HFD) exposure-impacts β-cell function, with a focus on the role of PRLR. In this study, we found that multiparous transgenic female mice with β-cell-specific PRLR deletion (βPrlr-/-) have impaired glucose tolerance when challenged with HFD. Unlike in pregnancy, where PRLR signaling upregulates β-cell proliferation and mass, we observed no difference in β-cell mass between the wild-type (βPrlr+/+) and mutant (βPrlr-/-) mice when metabolically stressed with HFD. However, βPrlr-/- mice showed blunted first-phase insulin release in vivo when challenged with glucose orally but not intraperitoneally, suggesting an impaired incretin effect. Moreover, there is a reduction in the expression of incretin hormone receptor, Glp-1r, and several of its upstream regulators, such as E2f1, Nkx6.1, Pax6, Pparγ, and Tcf7l2. Interestingly, isolated islets from βPrlr-/- mice showed intact in vitro glucose-stimulated insulin secretion (GSIS) but impaired incretin-potentiated GSIS. Islets from βPrlr-/- mice also had a lower insulin content and expressed lower levels of genes that regulate glucose metabolism. Together, these results suggested that PRLR signaling plays an important role in preserving β-cell function in mice exposed to metabolic stress by maintaining incretin receptor expression and insulin secretory capacity in β-cells.NEW & NOTEWORTHY Prolactin receptor (PRLR) signaling is crucial for β-cell adaptation to metabolic stresses from repeated pregnancies compounded by a high-fat diet (HFD). In PRLR-deficient β-cells, there is a reduction in insulin synthesis, expression of the gene that regulates GSIS, and incretin receptor Glp1r expression and response. This results in lower insulin secretion and impaired glucose tolerance. The link between PRLR and incretin receptor expression and function in islets is novel.

The role of prolactin receptor (PRLR) signaling in β-cell adaptation to maternal insulin resistance of pregnancy has been well demonstrated. Using transgenic mice with an inducible β-cell-specific Prlr deletion (βPrlr-/-), we found that intact PRLR, as found in βPrlr+/+ mice, were protected from developing glucose intolerance during pregnancy, and the main mechanism responsible for this PRLR-mediated effect is the up regulation of β-cell proliferation and insulin synthesis. Interestingly, studies in male mice and humans have found a link between diminished PRLR signaling and abnormal β-cell function. We aimed to determine whether PRLR has a role in regulating β-cell function outside of pregnancy, protecting β-cell against exposure to metabolic stressors.In this study, we found that β-cell-specific PRLR reduction resulted in impaired glucose tolerance in multiparous female mice challenged with a 12-week course of high-fat diet (HFD). Unlike in pregnancy, where PRLR signaling up regulates β-cell proliferation resulting in a greater β-cell mass, we observed no difference in β-cell mass between the wild type (βPrlr+/+) and mutant (βPrlr-/-) mice. In vitro glucose-stimulated insulin secretion using isolated islets from wild type (βPrlr+/+) and mutant (βPrlr-/-) mice showed comparable insulin response, but βPrlr-/- mice showed blunted first-phase insulin release in vivo, although only when challenged with glucose orally and not intraperitoneally, suggesting an impairment of the incretin effect. In support of the observed defect in incretin action, we found a reduction in expression of both incretin hormone receptors, Gipr and Glp-1r , and several of their upstream regulators, such as E2f1, Nkx6 . 1, Pax6, Pparγ , and Tcf7l2 . Islets from the mutant mice also have a lower insulin content and reduced levels of genes that regulate glucose metabolism. Together, these results suggested that PRLR signaling plays an important role in preserving β-cell function in mice exposed to metabolic stress by maintaining incretin receptor expression and insulin secretory capacity in β cells.### Competing Interest StatementThe authors have declared no competing interest.

The ability of β cells. to adapt to metabolic stressors is important in preventing diabetes. Our lab has previously shown that prolactin receptor (Prlr) signalling is required for β-cell adaptation to insulin resistance of pregnancy, mainly by regulating β-cell proliferation. Whether Prlr signalling is important for β-cell adaptation to physiologic stresses other than pregnancy is unknown. This study aimed to determine whether Prlr signalling is required for β-cell adaptation to the cumulative stresses of pregnancies followed by exposure to a high fat diet (HFD), a commonly observed scenario in humans.

The highly infectious nature of SARS-CoV-2 necessitates the use of widespread testing to control the spread of the virus. Presently, the standard molecular testing method (reverse transcriptase-polymerase chain reaction, RT-PCR) is restricted to the laboratory, time-consuming, and costly. This increases the turnaround time for getting test results. The study sought to develop a rapid, near-patient saliva-based test for COVID-19 with similar accuracy to that of standard RT-PCR tests. A lyophilized dual-target reverse transcription-loop-mediated isothermal amplification (RT-LAMP) test with fluorometric detection by the naked eye. The assay relies on dry reagents that are room temperature stable. A device containing a centrifuge, heat block, and blue LED light system was manufactured to reduce the cost of performing the assay. This test has a limit of detection of 1 copy/µL and achieved positive percent agreement of 100% [95% CI 88.43% to 100.0%] and negative percent agreement of 96.7% [95% CI 82.78% to 99.92%] on saliva. Saliva-Dry LAMP can be completed in 105 minutes. Precision, cross-reactivity, and interfering substances analysis met international regulatory standards. The combination of ease of sample collection, dry reagents, visual detection, low capital equipment cost, and excellent analytical sensitivity make Saliva-Dry LAMP particularly useful for resource-limited settings.

The coronavirus-2019 (COVID-19) pandemic has had significant impact on research directions and productivity in the past 2 years. Despite these challenges, since 2020, more than 2,500 peer-reviewed articles have been published on pancreatic islet biology. These include updates on the roles of isocitrate dehydrogenase, pyruvate kinase and incretin hormones in insulin secretion, as well as the discovery of inceptor and signalling by circulating RNAs. The year 2020 also brought advancements in in vivo and in vitro models, including a new transgenic mouse for assessing beta-cell proliferation, a "pancreas-on-a-chip" to study glucose-stimulated insulin secretion and successful genetic editing of primary human islet cells. Islet biologists evaluated the functionality of stem-cell-derived islet-like cells coated with semipermeable biomaterials to prevent autoimmune attack, revealing the importance of cell maturation after transplantation. Prompted by observations that COVID-19 symptoms can worsen for people with obesity or diabetes, researchers examined how islets are directly affected by severe acute respiratory syndrome coronavirus 2. Herein, we highlight novel functional insights, technologies and therapeutic approaches that emerged between March 2020 and July 2021, written for both scientific and lay audiences. We also include a response to these advancements from patient stakeholders, to help lend a broader perspective to developments and challenges in islet research.

Pancreatic islets adapt to insulin resistance of pregnancy by up regulating β-cell mass and increasing insulin secretion. Previously, using a transgenic mouse with global, heterozygous deletion of prolactin receptor (Prlr+/−), we found Prlr signaling is important for this adaptation. However, since Prlr is expressed in tissues outside of islets as well as within islets and prolactin signaling affects β-cell development, to understand β-cell-specific effect of prolactin signaling in pregnancy, we generated a transgenic mouse with an inducible conditional deletion of Prlr from β-cells. Here, we found that β-cell-specific Prlr reduction in adult mice led to elevated blood glucose, lowed β-cell mass and blunted in vivo glucose-stimulated insulin secretion during pregnancy. When we compared gene expression profile of islets from transgenic mice with global (Prlr+/−) versus β-cell-specific Prlr reduction (βPrlR+/−), we found 95 differentially expressed gene, most of them down regulated in the Prlr+/− mice in comparison to the βPrlR+/− mice, and many of these genes regulate apoptosis, synaptic vesicle function and neuronal development. Importantly, we found that islets from pregnant Prlr+/− mice are more vulnerable to glucolipotoxicity-induced apoptosis than islets from pregnant βPrlR+/− mice. These observations suggest that down regulation of prolactin action during pregnancy in non-β-cells secondarily and negatively affect β-cell gene expression, and increased β-cell susceptibility to external insults.

The highly infectious nature of SARS-CoV-2 necessitates the use of widespread testing to control the spread of the virus. Presently, the standard molecular testing method (reverse transcriptase-polymerase chain reaction, RT-PCR) is restricted to the laboratory, time-consuming, and costly. This increases the turnaround time for getting test results. This study sought to develop a rapid, near-patient saliva-based test for COVID-19 (Saliva-Dry LAMP) with similar accuracy to that of standard RT-PCR tests. A lyophilized dual-target reverse transcription-loop-mediated isothermal amplification (RT-LAMP) test with fluorometric detection by the naked eye was developed. The assay relies on dry reagents that are room temperature stable. A device containing a centrifuge, heat block, and blue LED light system was manufactured to reduce the cost of performing the assay. This test has a limit of detection of 1 copy/µL and achieved a positive percent agreement of 100% [95% CI 88.43% to 100.0%] and a negative percent agreement of 96.7% [95% CI 82.78–99.92%] relative to a reference standard test. Saliva-Dry LAMP can be completed in 105 min. Precision, cross-reactivity, and interfering substances analysis met international regulatory standards. The combination of ease of sample collection, dry reagents, visual detection, low capital equipment cost, and excellent analytical sensitivity make Saliva-Dry LAMP particularly useful for resource-limited settings.