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Gene Therapies: Diabetes Mellitus


Diabetes mellitus is a group of metabolic diseases causing a person to have high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. It's also a disease of the immune system. What are the warning signs?

Diabetes Mellitus affects about 8 percent of the U.S. population or 25 million, 285 million worldwide. It is estimated that half of all Americans will have diabetes by 2020.

Polycystic ovarian syndrome is a common hormone problem in overweight women of child-bearing age. It is often associated with infertility.

The diseases are often chronic, or even life long, and require a Diabetes Fit For Life strategy.


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High blood sugar produces the classical signs and symptoms of diabetes: thirst, hunger, weight loss, frequent urination...

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External Diabetes Info Links

Diabetes and infertility may be linked

New treatments for diabetes.

Recent stem cell diabetes research has resulted in reversal of the condition.

Link here to see how the symptoms of this deadly disease can be managed.

If you have high blood sugar there are many ways to control it.

But life can be enjoyed with diabetes.

Living with diabetes can be a challenge


Type 2 diabetes mellitus is a consequence of a seismic shift in lifestyle beginning about ten thousand years ago

The transition from hunting and gathering food to farming and raising animals, then eating the fruit of that labor. What are the causes of diabetes? The complications of diabetes?

Before the shift, neolithic hunter gatherers gorged food to store body fat in good times to ward off starvation in lean times. Body fat was life insurance!

Today, gobbling food in excess has developed into a pathology linked to obesity, type 2 diabetes, heart disease, stroke and chronic hand-to-mouth couch potato-itis.



Type 1 Diabetes Mellitus

Is a form of diabetes mellitus that results from autoimmune destruction of insulin producing beta cells of the pancreas. Incidence varies from eight to 17 per 100,000 in the U.S. It is fatal unless treated with insulin.



Genetic Origins

CMAH the evolutionary loss of function of CMP-NeuAc hydroxylase-like protein about one million years ago was a genetic adaptation essential for early human survival.

Mutation of the enzyme was an adaptation selected to store as much fat in the body as possible for times when food was scarce. Humans are the only mammals with this mutation.

Millions of years ago fat storage was life insurance. Today it makes modern humans prone to obesity and diabetes.

The mutation contributes to the failure of insulin-producing pancreatic beta cells in modern overweight humans, a key factor in the development of type 2 diabetes.

Wnt Signaling Pathway plays a role in the development of the pancreas. The pathway is a series of protein interactions that control several genes.

It is up-regulated in insulin producing cells in the pancreas of adults with type 2 diabetes, and in the expression c-myc gene, which has been implicated in the destruction of insulin-producing beta cells.

When the pancreas produces more insulin to counteract these negative effects it becomes overworked, slowing or stopping insulin release leading to Type 2 diabetes

  • PGC1-Alpha and Beta Genes Code for proteins in the mitochondria. The genes showed reduced expression in people with diabetes tipping the scale to insulin resistance.
  • PDEF Fat cells release a protein called platelet-derived growth factor that leads to development of Type 2 diabetes. The protein causes muscles and the liver to become desensitized to insulin.

Gene Therapies

The expression of genes can be up-regulated or down-regulated by agonists or antagonists called ligands.
  • KLF14 Gene Is the master switch controlling expression of multiple genes found in fat tissues linked to a range of traits: obesity, cholesterol, insulin and glucose levels. Manipulation of the gene results fat suppression and improved insulin sensitivity.
  • PPAR-Gamma Peroxisome proliferator activated receptor has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer.
  • Suppression of the protein by sirtuin induces calorie restriction causing weight loss. Resveratrol induces calorie restriction, muscle enhancement and endurance.

    AMPK Activated protein kinase is a master regulator protein of metabolism. When a cell is low on fuel, AMPK shuts down processes that use energy and turns on processes that produce energy.

    It binds directly to sites on chromosomes called promoters that regulate gene expression related to cell metabolism, and has implications for obesity, diabetes and cancer.

    CCL22 or Chemokine (C-C motif) ligand 22 gene Cytokines are proteins involved in immunoregulatory and inflammatory processes. The gene encodes a protein called CCL22.

    When the protein is increased in areas of the pancreas that produce insulin it blocks the immune attack that causes type 1 diabetes. CCL22 attracts T-regulatory cells to inhibit the immune response.

    Tmem27 is a gene that encodes the transmembrane protein Tmem27. Beta cells of the pancreas die when the protein is removed from its outer surface, or plasma membrane.

    Bace2, an enzyme residing on the plasma membrane, can destroy Tmem27. A Bace2 inhibitor blocked the enzyme’s activity and stimulated the regrowth of beta cells. Regenerating beta cells and increased insulin production is diabetes therapy.


    Immune System Manipulation

  • Immune System Abnormalities Autoimmune disease like Type 1 diabetes are caused when lymphocyte immune cells destroys the body’s tissues. Type 1 diabetes mellitus is caused by loss of the insulin-producing beta cells in the pancreas leading to insulin deficiency.
  • TNF the expression of immune-system modulator tumor necrosis factor led to the death of the T cells responsible for destroying insulin-producing pancreatic islets. The procedure is now in clinical trials as therapy for Type 1 diabetes.
  • TORC 2 is a gene that encodes transducers of regulated cAMP response element binding protein (CREB). TORC2 is a pathway that inhibits the production of glucose.
  • TORC2 activates a protein called Akt that causes proteins that take sugar from the blood to move to the cell surface. Lack of the gene for Akt causes development of diabetes-like symptoms.
  • People with Type 2 diabetes do not respond to insulin. AKT activation is a key step in metabolic pathway linked to diabetes. Lack of ATK gene causes development of diabetes
  • Beta Cell Deletion Deletion of beta cell lymphocytes using CD20-specfic antibody delayed or reduced onset of Type 1 diabetes. The treatment increased numbers of regulatory T and B cells.
  • Anti-CD20 Type 2 diabetes is being redefined as an autoimmune disease. An antibody called called Anti-CD20, targeted and eliminated mature B cells in the immune system. The antibody stopped type 2 diabetes in a mouse model restoring blood sugar levels to normal.
  • Anti-CD20, available in the U.S. under the trade name Rituxan and MabThera, is already approved as a treatment for some autoimmune diseases in humans.

    Immune System Reset Bone marrow stem cells were taken from 15 patients with Type 1 diabetes. They were given cytotoxan to completely destroy their immune systems.

    The stem cells were re-injected into the blood streams of the patients reestablishing their immune systems. Fourteen of 15 patients remain insulin independent.


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