Here, we investigated transcriptional and trafficking mechanisms of human islet amyloid polypeptide (hIAPP) in normal and stressed β-cells. In high glucose-challenged human islets and rat insulinoma cells overexpressing hIAPP, cell fractionation studies revealed increased accumulation of hIAPP. Unexpectedly, a significant fraction (up to 22%) of hIAPP was found in the nuclear soluble and chromatin-enriched fractions of cultured human islet and rat insulinoma cells. The nucleolar accumulation of monomeric forms of hIAPP did not have any adverse effect on the proliferation of β-cells nor did it affect nucleolar organization or function. However, intact nucleolar organization and function were essential for hIAPP expression under normal and ER-stress conditions as RNA polymerase II inhibitor, α-amanitin, reduced hIAPP protein expression evoked by high glucose and thapsigargin. Promoter activity studies revealed the essential role of transcription factor FoxA2 in hIAPP promoter activation in ER-stressed β-cells. Transcriptome and secretory studies demonstrate that the biosynthetic and secretory capacity of islet β-cells was preserved during ER stress. Thus, the main reason for increased intracellular hIAPP accumulation is its enhanced biosynthesis under these adverse conditions.

Amyloidosis is a common pathological event in which proteins self-assemble into misfolded soluble and insoluble molecular forms, oligomers and fibrils that are often toxic to cells. Notably, aggregation-prone human islet amyloid polypeptide (hIAPP), or amylin, is a pancreatic hormone linked to islet β-cells demise in diabetics. The unifying mechanism by which amyloid proteins, including hIAPP, aggregate and kill cells is still matter of debate. The pathology of type-2 diabetes mellitus (T2DM) is characterized by extracellular and intracellular accumulation of toxic hIAPP species, soluble oligomers and insoluble fibrils in pancreatic human islets, eventually leading to loss of β-cell mass. This review focuses on molecular, biochemical and cell-biology studies exploring molecular mechanisms of hIAPP synthesis, trafficking and degradation in the pancreas. In addition to hIAPP turnover, the dynamics and the mechanisms of IAPP–membrane interactions; hIAPP aggregation and toxicity in vitro and in situ; and the regulatory role of diabetic factors, such as lipids and cholesterol, in these processes are also discussed.

Due to the COVID-19 pandemic, many university-level chemistry laboratory experiments transitioned online. This created an educational challenge because students are unable to access reagents and instruments typical in a university lab setting. It is also difficult for students to connect theory to practice since real-lab experimentation is not possible in a virtual online for-mat. In our online Introductory Quantitative Analysis Laboratory course (GW Chem 2123W) in spring 2021, students were required to design and perform an experiment that could be safely conducted at home which can also demonstrate key princi-ples of quantitative analysis. Herein, we conducted a reliable at-home experiment that utilizes university-level acid/base titra-tion techniques to determine the acetic acid concentration in white vinegar. The experiment used sodium bicarbonate in the form of baking soda to titrate the Whole Foods white vinegar which is advertised to contain 6% of acetic acid. We reliably obtained an equivalence point for the titration from which the actual concentration of acetic acid in the vinegar was calculated with error analysis to be 19% higher than the advertised value. The analytical techniques demonstrated in this experiment supplement practical knowledge of acid/base techniques learned in the online classroom and prompt adoption of this meth-odology in online laboratory curriculum. This experiment can also be readily applied to measure other acidic solutions such as vinegar and juice for at-home experiment

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