Research Highlights January February 2019

A protein that assists in the process of insulin folding has just been discovered in a new study

A protein that assists in the process of insulin folding has just been discovered in a new study conducted by researchers at the Department of Biomedical Sciences, University of Copenhagen. The new research results have just been published in the scientific journal Diabetes.

Insulin is produced in the beta cells of the pancreas. The hormone is produced as a precursor called proinsulin. For proinsulin to mature into functional insulin, it needs to be folded and processed correctly to acquire the right structure with assistance from proteins that are termed chaperones. The researchers have now discovered and identified such a chaperone. A proinsulin chaperone termed glucose-regulated protein GRP94.

In the study the researchers removed or inhibited the protein GRP94 in to see what happened with the proinsulin and the cells. They observed that the proinsulin was not folded correctly and the beta cells did not secrete sufficient amounts of insulin. The researchers were surprised though to learn that removal of GRP94 did not affect cell viability. Nothing happened to the cells after they had removed the protein.

According to the researchers, the research results may make it possible in the future to manipulate the process from proinsulin to insulin in the body’s beta cells. If you can use medicine to inhibit the assistant protein, the result would be reduced insulin secretion. This would be useful in connection with conditions like hyperinsulinemia, where the body produces too much insulin. In the long term, they also hope the new knowledge will be useful in connection with types 1 and 2 diabetes.

Journal Reference:
Seyed Mojtaba Ghiasi, Tina Dahlby, Caroline Hede Andersen, Leena Haataja, Sólrun Petersen, Muhmmad Omar-Hmeadi, Mingyu Yang, Celina Pihl, Sophie Emilie Bresson, Muhammad Saad Khilji, Kristian Klindt, Oana Cheta, Marcelo J. Perone, Björn Tyrberg, Clara Prats, Sebastian Barg, Anders Tengholm, Peter Arvan, Thomas Mandrup-Poulsen, Michal Tomasz Marzec. The Endoplasmic Reticulum Chaperone Glucose-Regulated Protein 94 is Essential for Proinsulin Handling. Diabetes, 2019; db180671 DOI: 10.2337/db18-0671

PopPUNK a computational tool up to 200-fold faster for analyzing tens of thousands of bacterial genomes in a single run

Using k-mers, short sections of DNA length k, this software enables rapid estimation of the proportion of k-mers present in one genome that are also shared by another. Differences in k-mer content between genomes may represent changes to individual bases in otherwise similar stretches of DNA or differences in gene content. By calculating these relationships across isolates, the population structure of a species can be efficiently estimated.

Using a previously published data set of E. coli isolates collected over a ten-year study, PopPUNK was able to efficiently classify the prevalence of different strains in the population each year and identify the emergence of antibiotic-resistance strains over time.

Journal Reference:
Lees J, Harris S. Tonkin-Hill G, Gladstone R, Lo S, Weiser J, Corander J, Bentley S, Croucher N. Fast and flexible bacterial genomic epidemiology with PopPUNK. Genome Research, 2019 DOI: 10.1101/gr.241455.119

After university goes silent, diabetes journal retracts three papers

A group of researchers based in Italy has had three papers retracted for likely using the same images to represent different experimental conditions.

The retractions, in Diabetes, published by the American Diabetes Association (ADA), follow expressions of concern for the papers in early 2018 and the launch of an investigation by the authors’ institution into the work. The status of that investigation by Università degli Studi di Napoli Federico II, however, is unclear, as the university has stopped responding to the journal’s inquiries.

Here are the three now-retracted papers:
1. “The IR1152 mutant insulin receptor selectively impairs insulin action in skeletal muscle but not in liver,” cited 10 times, according to Clarivate Analytics’ Web of Science
2. “Prep1 Controls Insulin Glucoregulatory Function in Liver by Transcriptional Targeting of SHP1 Tyrosine Phosphatase,” cited 25 times
3. “Protein kinase C (PKC)-alpha activation inhibits PKC-zeta and mediates the action of PED/PEA-15 on glucose transport in the L6 skeletal muscle cells,” cited 54 times


New hope for stem cell approach to treating diabetes
Scientists working to develop more effective treatments for diabetes are turning to stem cells. Such cells can be transformed into cells that produce insulin. But there’s a major challenge: the amount of insulin produced by theses cells is difficult to control.

Now, by tweaking the recipe for coaxing human stem cells into insulin-secreting beta cells, a team of researchers at Washington University School of Medicine in St. Louis has shown that the resulting cells are more responsive to fluctuating glucose levels in the blood. When they transplanted the beta cells into mice that could not make insulin, the new cells began secreting insulin within a few days, and they continued to control blood sugar in the animals for months.

The new insulin-producing cells react more quickly and appropriately when they encounter glucose,” said principal investigator Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering. “The cells behave much more like beta cells in people who don’t have diabetes.” Millman was a part of a research team at Harvard that, in 2014, converted skin cells into stem cells and, in 2016, did the same thing with skin cells from a patient with diabetes. Each time, the stem cells were then treated with various growth factors to coax them into insulin-secreting beta cells. The beta cells, however, didn’t work as well as the researchers had hoped.

Millman said that if stem cell-derived beta cells are proven safe and effective for people with diabetes, his method of manufacturing the cells quickly could be ramped up to an industrial scale. In his laboratory alone, his team is able to grow and develop more than a billion beta cells in just a few weeks.

Journal Reference:
Leonardo Velazco-Cruz, Jiwon Song, Kristina G. Maxwell, Madeleine M. Goedegebuure, Punn Augsornworawat, Nathaniel J. Hogrebe, Jeffrey R. Millman. Acquisition of Dynamic Function in Human Stem Cell-Derived β Cells. Stem Cell Reports, 2019; DOI: 10.1016/j.stemcr.2018.12.012

Research Finds Extreme Opponents of GM Foods Know the Least but Think They Know the Most
People with the most extreme views opposing genetically modified (GM) foods think they know most about GM food science, but actually, they know the least, according to new research published in Nature Human Behaviour. The research was a collaboration between researchers at the Leeds School of Business at CU Boulder, Washington University in St. Louis, the University of Toronto, and the University of Pennsylvania.

Marketing and psychology researchers asked more than 2,000 U.S. and European adults for their opinions about GM foods. The surveys asked the respondents how well they thought they understood GM foods, then tested how much they actually knew with a battery of true-false questions on general science and genetics. The researchers found that despite the scientific consensus that GM foods are safe for human consumption, many people oppose their use. More than 90 percent of the respondents reported some level of opposition to GM foods.

“This result is perverse, but is consistent with previous research on the psychology of extremism,” said Philip Fernbach, the study’s lead author and professor of marketing at the Leeds School of Business. “Extreme views often stem from people feeling they understand complex topics better than they do.”

Nicholas Light, a Leeds School of Business PhD candidate in marketing suggests that changing people’s minds first requires them to appreciate what they do not know. He added that without this first step, educational interventions might not work very well to bring people in line with the scientific consensus.

Reference: CU Boulder Today

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