Can Artificial Cells Take Over for Lost Insulin-Secreting Cells?

artificial beta cells

Caption: Artificial beta cell, made of a lipid bubble (purple) carrying smaller, insulin-filled vesicles (green). Imaged with cryo-scanning electron microscope (cryo-SEM) and colorized.
Credit: Zhen Gu Lab

People with diabetes have benefited tremendously from advances in monitoring and controlling blood sugar, but they’re still waiting and hoping for a cure. Some of the most exciting possibilities aim to replace the function of the insulin-secreting pancreatic beta cells that is deficient in diabetes. The latest strategy of this kind is called AβCs, short for artificial beta cells.

As you see in the cryo-SEM image above, AβCs are specially designed lipid bubbles, each of which contains hundreds of smaller, ball-like vesicles filled with insulin. The AβCs are engineered to “sense” a rise in blood glucose, triggering biochemical changes in the vesicle and the automatic release of some of its insulin load until blood glucose levels return to normal.

In recent studies of mice with type 1 diabetes, researchers partially supported by NIH found that a single injection of AβCs under the skin could control blood glucose levels for up to five days. With additional optimization and testing, the hope is that people with diabetes may someday be able to receive AβCs through patches that painlessly stick on their skin.

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Feed a Virus, Starve a Bacterium?

Woman eating hot soup in bed

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Yes, the season of colds and flu is coming. You’ve probably heard the old saying “feed a cold and starve a fever.” But is that sound advice? According to new evidence from mouse studies, there really may be a scientific basis for “feeding” diseases like colds and flu that are caused by viruses, as well as for “starving” certain fever-inducing conditions caused by bacteria.

In the latest work, an NIH-funded research team found that providing nutrition to mice infected with the influenza virus significantly improved their survival. In contrast, the exact opposite proved true in mice infected with Listeria, a fever-inducing bacterium. When researchers forced Listeria-infected mice to consume even a small amount of food, they all died.

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Taking a New Look at Artificial Sweeteners

Packets of artificial sweetenersDiet sodas and other treats sweetened with artificial sweeteners are often viewed as guilt-free pleasures. Because such foods are usually lower in calories than those containing natural sugars, many have considered them a good option for people who are trying to lose weight or keep their blood glucose levels in check. But some surprising new research suggests that artificial sweeteners might actually do the opposite, by changing the microbes living in our intestines [1].

To explore the impact of various kinds of sweeteners on the zillions of microbes living in the human intestine (referred to as the gut microbiome), an Israeli research team first turned to mice. One group of mice was given water that contained one of two natural sugars: glucose or sucrose; the other group received water that contained one of three artificial sweeteners: saccharin (the main ingredient in Sweet’N Low®), sucralose (Splenda®), or aspartame (Equal®, Nutrasweet®). Both groups ate a diet of normal mouse chow.

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Protein Machines at Work

This video shows a molecular view of the reactions that take place inside the pyruvate dehydrogenase complex, a protein machine found in the cell’s powerhouse, the mitochondria. 3D imaging of this machine by high-resolution electron microscopy reveals how the different components essential for the reaction are organized. Watch the flexible arms move inside the protein machine as pyruvate (an essential compound made from glucose) gets converted into acetyl-CoA (a precursor to the cell’s energy supply).

Credit: Jacqueline Milne and Sriram Subramaniam, Laboratory of Cell Biology, National Cancer Institute; Donald Bliss, National Library of Medicine; NIH

References:

Molecular architecture and mechanism of an icosahedral pyruvate dehydrogenase complex: a multifunctional catalytic machine. Milne JL, Shi D, Rosenthal PB, Sunshine JS, Domingo GJ, Wu X, Brooks BR, Perham RN, Henderson R, Subramaniam S. EMBO J. 2002 Nov 1;21(21):5587-98.

Molecular structure of a 9-MDa icosahedral pyruvate dehydrogenase subcomplex containing the E2 and E3 enzymes using cryoelectron microscopy. Milne JL, Wu X, Borgnia MJ, Lengyel JS, Brooks BR, Shi D, Perham RN, Subramaniam S. J Biol Chem. 2006 Feb 17;281(7):4364-70.

Extended polypeptide linkers establish the spatial architecture of a pyruvate dehydrogenase multienzyme complex. Lengyel JS, Stott KM, Wu X, Brooks BR, Balbo A, Schuck P, Perham RN, Subramaniam S, Milne JL. Structure. 2008 Jan;16(1):93-103

 

The Diabetes Threat

The number of Americans diagnosed with type 2 diabetes rose from 1.5 million in 1958 to 18.8 million in 2010. That’s an increase of epidemic proportions. Even more disturbing, another 7 million Americans have type 2 diabetes, but don’t know it and, consequently, can’t take steps to control the disease. Altogether, over 8% of the U.S. population now has this potentially deadly metabolic condition.

  • Type 2 diabetes wreaks havoc on the body by raising the levels of glucose in the blood, increasing the risk of blindness, heart disease, kidney failure, nerve damage, and even Alzheimer’s disease.
  • Pre-diabetes is a condition in which blood glucose levels are higher than normal, but not high enough to be called diabetes. 79 million U.S. adults age 20 and older have pre-diabetes.
  • NIH studies have shown that losing just 6–7% of body weight and increasing physical activity can prevent or delay pre-diabetes from progressing to diabetes. 85% of people with diabetes are overweight.

Photo of a pair of sneakers with the text "November is National Diabetes Month -  Be Active - Make a plan to live well."