Insulin demand regulates β cell number via the unfolded protein response

Although stem cell populations mediate regeneration of rapid turnover tissues, such as skin, blood, and gut, a stem cell reservoir has not been identified for some slower turnover tissues, such as the pancreatic islet. Despite lacking identifiable stem cells, murine pancreatic β cell number expands in response to an increase in insulin demand. Lineage tracing shows that new β cells are generated from proliferation of mature, differentiated β cells; however, the mechanism by which these mature cells sense systemic insulin demand and initiate a proliferative response remains unknown. Here, we identified the β cell unfolded protein response (UPR), which senses insulin production, as a regulator of β cell proliferation. Using genetic and physiologic models, we determined that among the population of β cells, those with an active UPR are more likely to proliferate. Moreover, subthreshold endoplasmic reticulum stress (ER stress) drove insulin demand–induced β cell proliferation, through activation of ATF6. We also confirmed that the UPR regulates proliferation of human β cells, suggesting that therapeutic UPR modulation has potential to expand β cell mass in people at risk for diabetes. Together, this work defines a stem cell–independent model of tissue homeostasis, in which differentiated secretory cells use the UPR sensor to adapt organ size to meet demand.     

Inclusion body myositis in the rheumatology clinic

Inclusion body myositis is a rare sporadic inflammatory‐degenerative myopathy of the elderly. Despite being the commonest type of acquired myopathy after the age of 50, misdiagnosis is extremely common. The most frequent hurdle in identifying new cases is the wrong diagnosis of polymyositis or motor neuron disease. Novel insights into pathogenic mechanisms have heralded the quest for newer therapeutics as well as drug repurposing in this otherwise progressive disorder.     

Invasive pulmonary aspergillosis in an immunocompetent patient with severe dengue fever

We report a case of a 65-year-old female diagnosed with sever dengue fever. She started showing recovery from dengue fever with medical management. On day 6 of admission, she had leukocytosis, altered mental sensorium, and hemoptysis. Chest tomography showed air space consolidation with multiple nodules in the left upper and middle lobe sputum and bronchoalveolar lavage cultures were positive for Aspergillus flavus. The patient showed improvement with voriconazole and therapy was continued for 6 weeks.