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Biologists Wondered—How Old are Cells in an Organism?

Posted in Biological Engineering, Cell Biology, tagged , , , , , , on June 26, 2019| Leave a Comment »

Biologists Wondered—How Old are Cells in an Organism?

Reporter: Irina Robu, PhD

Scientists form Salk Institute discovered that the mouse brain, live and pancreas contain populations of cells and proteins with extremely long lifespans with some as old as neurons. The research was published in Cell Metabolism on June 6, 2019. The general idea is that most neurons in the brain do not divide during adulthood and experience a long lifespan and age-related decline. Yet, due to limitations the lifespan of cells outside of the brain was difficult to determine.

However, the researchers knew very well that neurons are not replaced during the lifespan, they used them as control to compare other non-dividing cells. The team used an electron isotope labeling with hybrid imaging method to visualize and quantify cell and protein age and turnover in the brain, pancreas and liver in the young and old rodent models.

To confirm that their method is correct, the scientist determined first the age of the neurons and then realized that the cells that line blood vessels, endothelial cells were as old as neurons. According to this research, it means that some non-neuronal cells do not replicate themselves throughout the lifespan. The pancreas, the organ responsible for maintaining blood sugar levels and secreting digestive enzymes showed cells of all ages. Still, some beta cells, replicate during the lifetime and are relatively young, while others do not divide and were long lived. Yet, delta cells found in stomach do not divide at all.
Unlike other type of cells, the liver cells have the capacity to regenerate during adulthood. The researchers expected to observe young liver cells, however the majority of liver cells were found to be as old as the animal, while the cells that line blood vessels and stellate like cells, another liver type cell were short lived.

But on the molecular level, a selection of long-lived cells contains protein complexes displaying age mosaicism. Due to the modern visualizing technologies, scientists were able to pinpoint the age of the cells and their supra-molecular complexes precisely. The ultimate goal to determining the age of the cells and sub-cellular structures is to provide insights into cell maintenance and repair mechanism and utilize these mechanisms to prevent or delay old age-linked decline of organs with limited cell regeneration.

SOURCE

https://www.salk.edu/news-release/how-old-are-your-organs-to-scientists-surprise-organs-are-a-mix-of-young-and-old-cells/

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Stem Cells Differentiated into Insulin-Producing Cells in Mice

Posted in stem cell biology and patient-specific, tagged , , , , , on March 3, 2019| Leave a Comment »

Stem Cells Differentiated into Insulin-Producing Cells in Mice

Reported: Irina Robu, PhD

Dr. Douglas Melton team from Harvard University funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases set out to transform stem cells into beta cells that have the potential to replace damaged beta cells. While scientists have been able to change stem cells into insulin-producing cells, these cells don’t have markers that indicate they are beta cells, and they aren’t responsive to glucose.

Since diabetes is a disorder of elevated blood sugars where the body does not harvest enough insulin to meet where the body does not harvest enough insulin to respond properly to the insulin being made. When blood glucose levels rise, beta cells in the pancreas normally make the hormone insulin. Insulin triggers cells throughout the body to take up sugar from the blood. In type 2 diabetes, the most common form, tissues in the body lose their sensitivity to insulin, and pancreatic beta cells can’t make enough insulin to keep glucose levels in check. In type 1 diabetes, the body’s own immune system attacks and destroys beta cells. High blood glucose levels can lead to heart disease, blindness, and other health problems over time.

One approach to treat diabetes is to replace destroyed beta cells. Transplanted human pancreatic cells from deceased donors have been successfully used to treat people with type 1 diabetes. But this method is restricted by the accessibility of donor cells and the side effects of immunosuppression. The other approach is to develop functioning beta cells from stem cells which have the potential to transform into many different cell types. These cells can grow indefinitely in the laboratory and can differentiate, into any cell type found in the body.
In this experiment, the researchers grew a human embryonic stem cell line and 2 human-induced pluripotent stem cell lines in a culture system that allowed them to produce large numbers of cells. The researchers tested more than 150 combinations of over 70 compounds to figure out a method to produce functional human beta cells from the cultured stem cells which when added in exact combinations over a period of several weeks, they transformed human pluripotent stem cells into beta cells that functioned similarly to normal adult beta cells.

The cultured beta cells had specific markers that were found on normal beta cells which displayed changes in calcium levels when exposed to glucose and packaged insulin into granules. However, when transplanted into mice these cells secreted insulin in response to glucose. However, when the cells were transplanted into diabetic mice, abnormally high blood glucose levels lowered. More work is needed to develop these cells for clinical use. However, at this point they can serve as a useful screening tool for diabetes drugs.

SOURCE
http://www.frontlinegenomics.com/news/26168/stem-cells-turned-into-insulin-producing-cells-in-mice/

 

 

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Congenital Hyperinsulinism

Posted in Biological Networks, Gene Regulation and Evolution, Chemical Genetics, Genome Biology, Genomic Testing: Methodology for Diagnosis, Medical and Population Genetics, Nutrigenomics, Personalized and Precision Medicine & Genomic Research, Population Health Management, Genetics & Pharmaceutical, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, tagged , , , , , , , , , , , on February 11, 2013| Leave a Comment »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Congenital hyperinsulinism is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and most become apparent in early infancy. The severe forms can cause obvious problems in the first hour of life, but milder forms may not be detected until adult years. Mild cases can be treated by frequent feedings, more severe cases can be controlled by medications that reduce insulin secretion or effects, and a minority of the most severe cases require surgical removal of part or most of the pancreas to protect the brain from damage due to recurrent hypoglycemia.

Types of congenital hyperinsulinism:

1. Transient neonatal hyperinsulinism

2. Focal hyperinsulinism

  • Paternal SUR1 mutation with clonal loss of heterozygosity of 11p15
  • Paternal Kir6.2 mutation with clonal loss of heterozygosity of 11p15

3. Diffuse hyperinsulinism

a. Autosomal recessive forms

  • i. SUR1 mutations
  • ii. Kir6.2 mutations
  • iii. Congenital disorders of glycosylation

b. Autosomal dominant forms

4. Beckwith-Wiedemann syndrome (thought to be due to hyperinsulinism but pathophysiology still uncertain: 11p15 mutation or IGF2 excess)

Congenital hyperinsulinism (CHI or HI) is a condition leading to recurrent hypoglycemia due to an inappropriate insulin secretion by the pancreatic islet beta cells. HI has two main characteristics:

  • a high glucose requirement to correct hypoglycemia and
  • a responsiveness of hypoglycemia to exogenous glucagon.

HI is usually isolated but may be rarely part of a genetic syndrome (e.g. Beckwith-Wiedemann syndrome, Sotos syndrome etc.). The severity of HI is evaluated by the glucose administration rate required to maintain normal glycemia and the responsiveness to medical treatment. Neonatal onset HI is usually severe while late onset and syndromic HI are generally responsive to a medical treatment. Glycemia must be maintained within normal ranges to avoid brain damages, initially, with glucose administration and glucagon infusion then, once the diagnosis is set, with specific HI treatment. Oral diazoxide is a first line treatment.

In case of unresponsiveness to this treatment, somatostatin analogues and calcium antagonists may be added, and further investigations are required for the putative histological diagnosis:

  • pancreatic (18)F-fluoro-L-DOPA PET-CT and
  • molecular analysis.

Indeed, focal forms consist of a focal adenomatous hyperplasia of islet cells, and will be cured after a partial pancreatectomy.

Diffuse HI involves all the pancreatic beta cells of the whole pancreas. Diffuse HI resistant to medical treatment (octreotide, diazoxide, calcium antagonists and continuous feeding) may require subtotal pancreatectomy which post-operative outcome is unpredictable.

The genetics of focal islet-cells hyperplasia associates

  • a paternally inherited mutation of the ABCC8 or
  • the KCNJ11 genes, with
  • a loss of the maternal allele specifically in the hyperplasic islet cells.

The genetics of diffuse isolated HI is heterogeneous and may be

  • recessively inherited (ABCC8 and KCNJ11) or
  • dominantly inherited (ABCC8, KCNJ11, GCK, GLUD1, SLC16A1, HNF4A and HADH).

Syndromic HI are always diffuse form and the genetics depend on the syndrome. Except for HI due to

  • potassium channel defect (ABCC8 and KCNJ11),

most of these HI are sensitive to diazoxide.

The main points sum up the management of HI:

  • i) prevention of brain damages by normalizing glycemia and
  • ii) screening for focal HI as they may be definitively cured after a limited pancreatectomy.

Source & References:

http://en.wikipedia.org/wiki/Congenital_hyperinsulinism

http://www.ncbi.nlm.nih.gov/pubmed/20550977

 

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