Hope for diabetics: insulin can be synthesized in the intestine
The results obtained by researchers at Columbia University, working under the guidance of Professor Domenico Accili, indicate that the intestinal cells of patients with type 1 diabetes can be taught to synthesize insulin.
Type 1 diabetes is an autoimmune disease that leads to the death of insulin-producing cells of the pancreas. The loss of these cells is irreversible and to control blood glucose levels, patients have to resort to regular insulin injections throughout their lives.
The goal sought by specialists engaged in the search for methods of treating this disease is to replace the lost cells with new ones capable of releasing a sufficient amount of insulin into the patient's bloodstream. Scientists have already learned how to turn embryonic stem cells into insulin-producing ones, but these cells are unsuitable for transplantation to patients. The problem is that they are not able to regulate the intensity of insulin synthesis in response to changes in glucose levels. In the patient's body, such cells would secrete insulin unnecessarily, which is fraught with life-threatening hypoglycemia.
The progenitor cells included in the tissues of the gastrointestinal tract are capable of giving rise to a wide range of specialized cells, including cells synthesizing serotonin, gastric inhibitory peptide (it enhances the response of beta cells to the action of glucose) and other hormones released into the lumen of the gastrointestinal tract and blood flow. It turned out that some of these mouse intestinal progenitor cells have an amazing ability to turn into insulin-producing cells.
The researchers achieved this result by inactivating the Foxo1 gene (known for its participation in determining cell differentiation) in the progenitor cells of the small intestine of mice. Moreover, the described effect was observed not only at the early stages of animal development, but also when manipulating adult mice, although in the first case, inactivation of Foxo1 ensured the appearance of more insulin-producing cells.
In an image from the Columbia University Medical Center website, insulin–producing intestinal cells express glucokinase, a key enzyme in the glucose processing process. Insulin is colored red, glucokinase is green. Yellow coloring appeared in places of mixing colors.
The mechanisms of this phenomenon are still unclear to scientists, but they note that the forming cells have functional receptors that register the concentration of glucose, which excludes the possibility of synthesizing an excessive amount of insulin.
Insulin synthesized by insulin-producing intestinal cells is released into the bloodstream in an amount sufficient to normalize the blood glucose level of a mouse model of diabetes.
Moreover, the gastrointestinal tract is partially protected from the activity of the immune system, which may prevent the autoimmune destruction of newly formed insulin-producing intestinal cells in patients with type 1 diabetes.
To turn the identified mechanism into an effective therapy method that will allow not only pediatric but also adult patients to be cured of diabetes, it is necessary to find a drug that safely and effectively blocks the activity of the Foxo1 gene in target cells. The researchers are confident that this is possible, since they have already succeeded in laboratory conditions with the help of a chemical compound (its name is not disclosed for obvious reasons) to inhibit the synthesis of Foxo1 in progenitor cells and turn them into insulin-producing cells.
Article by Chutima Talchai et al. Generation of functional insulin-producing cells in the gut by Foxo1 ablation is published in the preliminary on-line version of the journal Nature Genetics.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Columbia University: New Approach to Treating Type I Diabetes? Columbia Scientists Transform Gut Cells into Insulin Factories.
16.03.2012