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Beta Cell Regeneration - Novel Therapy in Diabetes

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6 min read


Diabetes is largely caused by the reduction of insulin-producing pancreatic beta cells. Beta cell transplantation is done with the help of human stem cells.

Written by

Dr. Palak Jain

Medically reviewed by

Dr. Kanani Darshan Jayantilal

Published At June 16, 2023
Reviewed AtJune 26, 2023


An important public health issue on a global scale is diabetes. The World Health Organization estimates that 440 million people worldwide have diabetes, with type 2 diabetes accounting for the vast majority of cases, while type 1 diabetes affects five percent of people. The majority of people with type 2 diabetes and most type 1 diabetes patients experience decreased numbers of insulin-secreting pancreatic beta cells. Additionally, only 30 percent of individuals with type 1 diabetes or type 2 diabetes meet the ADA (American Diabetes Association) treatment objectives for glycemic control using currently accessible medications. Due to these factors, attempts have been made to restore the beta cell mass in type 1 diabetes patients to normal using whole pancreas transplants from organ donors, transplants of isolated human pancreatic islets, transplants of beta cells derived from human embryonic or induced pluripotent stem cells, and through the use of gene therapy.

Through the development of medications that can stimulate human beta cells to divide, grow, or regenerate. The latter area of developing drugs to regenerate human beta cells is developing quickly. There is a general consensus that it is now possible to stimulate the regeneration of adult human beta cells, although there are still a number of grey areas and difficulties.

How Is Beta Cell Mass Reduced in Diabetes?

The majority of people with obesity and insulin resistance do not have diabetes, even though insulin resistance is a significant contributor to type 2 diabetes. This suggests that insulin resistance is only one of several factors that contribute to the development of type 2 diabetes. Although there is significant overlap with normal, autopsy investigations have shown that some people with type 2 diabetes have pancreatic beta cell mass reductions of up to 40 to 60 percent when compared to age, sex, and body mass index-matched normal.

Many type 2 diabetes patients have decreased beta cell mass, probably due to a combination of

1. Genetic propensity to decreased beta cell mass or function, as demonstrated by GWAS (genome-wide association) research.

2. Poor beta cell mass development in prenatal and childhood years.

3. Beta cell de-differentiation brought on by glucotoxicity, lipotoxicity, and endoplasmic reticulum stress, all brought on by an increased need for insulin brought on by insulin resistance, an excessive caloric intake, or combinations of the factors listed.

Due to autoimmune destruction and dedifferentiation of human beta cells, type 1 diabetes also decreases beta cell mass. Estimates of the residual beta cell mass in type 1 diabetes are based on autopsy research and range from 2 percent to 40 percent. Notably, most of those with type 1 diabetes continue to produce some insulin even after 50 to 80 years, and the vast majority also retain some remnant beta cells at autopsy.

What Are the Strategies For Stimulation of Beta Cells Replication?

Various strategies have been examined to quickly and effectively replenish cell masses. Numerous factors encourage cell proliferation. According to studies, exogenous stimuli can be administered to young mice to increase cell growth. Uncertainty exists over the ability of external stimuli to stimulate the proliferation of adult rodent cells. According to some research, the primary source of new insulin-expressing cells in adult mice is either pancreatectomy-induced cell replication or cell death. According to other investigations, numerous diabetogenic injuries, such as partial pancreatectomized, Streptozotocin injection, and pancreatic duct ligation, have not increased cell proliferation in adult mice.

Several possible agents for the promotion of cell replication have been found by chemical screening. Among these substances are DYRK1A inhibitors, such as Harmine, Aminopyrazine compounds, and 5-iodotubercidin, which promote cell proliferation by obstructing calcineurin/Nfat/Dyrk1a signaling. Osteoprotegerin and Denosumab promote human cell proliferation by suppressing the receptor activator of the nuclear factor - B ligand pathway. Furthermore, silencing CDKN2C/p18 or CDKN1A/p21 promoted the cell-cycle re-entry of dormant adult human cells, as shown by high-throughput RNAi (ribonucleic acid) screening.

How Are Pancreatic Progenitors Cells Helpful in the Treatment of Diabetes Mellitus?

A potential strategy for treating diabetes-related cell insufficiency is to increase cell proliferation. However, given the nearly total loss of beta cells in type-1 diabetes, stimulating beta cell neogenesis may be a more practical method for treating diabetes than increasing beta cell proliferation. Neogenesis is the process through which insulin-producing cells are created, either through conversion from other pancreatic cells or differentiation from stem/progenitor cells. Even though there is evidence that all pancreatic cell lineages, including ductal, endocrine, and exocrine, are descended from embryonic multipotent progenitors, the existence of adult cell progenitors is still the most contentious issue in diabetes research. Numerous investigations have demonstrated that progenitor cells are the source of cells. The pancreatic ductal epithelium is the putative progenitor of islet and acinar tissues after birth.

New ductal cells that express Pdx1, Hnf6, Foxa2, Tcf1/2, and Sox9, markers of the embryonic pancreatic epithelium, are found in the foci of regeneration brought on by partial pancreatectomized, leading to the development of new pancreatic lobes. These actions imply that new ductal cells serve as the progenitors for the pancreas' regenerative tissue.

What Are the Drugs Used for the Stimulation of Beta Cell Conversion?

Glutamate decarboxylase converts glutamate into the inhibitory neurotransmitter gamma-aminobutyric acid found in the central nervous system (glutamic acid decarboxylase). Pancreatic islet cells, particularly cells, contain high concentrations of Gamma-Aminobutyric acid and Glutamic acid decarboxylase. A significant autoantigen in type-1 diabetes is an isoform of glutamic acid decarboxylase called glutamic acid decarboxylase 65. Gamma-aminobutyric acid encourages cell multiplication and prevents cell death in mice models of streptozotocin-induced diabetes and transplanted human islets. In the plasma membranes of islet cells, gamma-aminobutyric acid produced from cells interacts with and activates the metabotropic G-protein-coupled receptor GABAB and the ionotropic receptor GABAA (a calcium ion channel). When ligands bind to receptors, insulin secretion from cells increases, and glucagon release from cells is suppressed.

Furthermore, gamma-aminobutyric acid administration increases islet mass and cell-like numbers while simultaneously causing the loss of cells in transplanted human islets. However, more research is needed to fully understand the mechanism of gamma-aminobutyric acid's role in transforming cells into cells. Gamma-aminobutyric acid may act on gamma-aminobutyric acid A receptors in cells, as evidenced by its capacity to inhibit Arx expression. Additionally, via modulating the release of cytokines from CD4+ T cells and human peripheral blood mononuclear cells, gamma-aminobutyric acid may function as an immunosuppressive regulator in type-1 diabetes. In conclusion, the treatment of gamma-aminobutyric acid boosts the conversion of cells to cells, promotes the replication of cells, and inhibits immunological responses in mouse models of diabetes. Given these effects, gamma-aminobutyric acid may have an anti-diabetic effect and be useful in treating type-1 diabetes. Artemisinin is the potential activator of the conversion of cells to cells. According to one study, Artemisinin impairs cell identity. It causes insulin to be expressed in cells by causing Arx to move from the nucleus to the cytoplasm, which is subsequently blocked. Additionally, Artemisinin enhances gamma-aminobutyric acid receptor signaling in a gephyrin-dependent way during the transdifferentiation of cells into like cells.

How Does DYRK1A Help in Treating Diabetes Mellitus?

The four transcription factors in the nuclear factor activated in the T-cells family are phosphorylated by the kinase DYRK1A and other substrate proteins. Nuclear factor activated in the T-Cells typically exist in the cytoplasm and are phosphorylated. Calmodulin is triggered upon calcium entry into beta cells, which may occur in reaction to glucose, sulfonylureas, or GLP1 receptor agonists. Calmodulin then activates the phosphatase calcineurin. Calcineurin dephosphorylates nuclear factor activated in the T-cells, allowing them to enter the nucleus where they bind to regulatory regions of target genes, activating genes encoding cyclins and cdks (such as cdk1, cyclin A, and cyclin E) and repressing genes encoding cell cycle inhibitors (such as p57KIP2, and p15INK4). This results in the stimulation of beta cell proliferation.

The kinase DYRK1A phosphorylates the four transcription factors in the nuclear factor activated in the T-Cells family and other substrate proteins. The nuclear factor activated in the T-Cells is generally phosphorylated and found in the cytoplasm. Calmodulin is released when calcium enters beta cells, such as in response to glucose, sulfonylureas, or glucogen-like peptide-1 receptor agonists. The phosphatase calcineurin is then activated by calmodulin. Calcineurin dephosphorylates nuclear factor activated in the T-cells, allowing them to reach the nucleus where they bind to regulatory areas of target genes, activating and repressing genes encoding cell cycle inhibitors and cyclins (such as cdk1, cyclin A, and cyclin E) (such as p57KIP2, and p15INK4). As a result, beta cell proliferation is stimulated.

Is Beta Cell Regeneration Therapy Safe?

In the use of DYRK1A in the past, the two main natural sources of harmine for inhibitors are the Middle Eastern plant Peganum harmala, which is used in incense, oral infusions, and inhalants, and a South American vine known as Banisteriopsis caapi, from which ayahuasca is derived. Ayahuasca has been the subject of the most research in the West. South American shamans have been employing substances linked to harmine for at least a thousand years. Ayahuasca is made from the vine Banisteriopsis caapi, which contains harmine, combined with the leaves of Psychotria Viridis, which contain 5,5-dimethyltryptamine. It can be smoked, snorted as a powder, or ingested orally as a tea or infusion. Most of the popular and academic literature on ayahuasca is from the United States. Traditional ayahuasca causes pleasant mood enhancement and visual hallucinations in the right doses. Higher doses may result in nausea, vomiting, diarrhea, sleepiness, and diminished awareness. Importantly, there are few or no instances of chronic disease or mortality despite the extensive use over a century's time.


Numerous ways for treating diabetes with cell deficiency have been suggested by cell regeneration. However, the majority of these techniques have only been effectively used on animals. While some diabetic therapy plans have worked in rodent models, the majority have fallen short in people. The fundamental causes of clinical failures are known to be type-1 diabetes autoimmunologic characteristics. Specifically, diabetogenic T cells constantly recognize and kill neogenetic cells, causing these new cells to die. Fortunately, methods and technologies for safeguarding newly transplanted islet cells have advanced.

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Dr. Kanani Darshan Jayantilal
Dr. Kanani Darshan Jayantilal

Family Physician


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