Introduction: What they say
A study from the Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel shows that “PAX6 maintains ß cell identity by repressing genes of alternative islet cell types.” This research paper was published, in the 12 December 2016 issue of the journal “Journal of Clinical investigations” [One of the best research journals in Clinical Medicine with an I.F of 12.575], by Prof. Yuval Dor and Avital Swisa and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: A sweet way to stay free of TIIDM: Trehalose, a disaccharide and artificial sweetener found in mushroom and others, increases Pax6 and insulin expression, decreases the levels of glucagon, ghrelin and Somatostatin, reduces metabolic stress, improves insulin sensitivity, promotes glucose homeostasis and prevents progression to TIIDM via down regulation of its target gene
From Significance of the study to Public health relevance:
Given that: (1) more than 387 million people worldwide are affected by Diabetes mellitus (DM); (2) Diabetes is going to be one of the top 10 causes of death by 2030; (3) the life-long painful injection/drug treatment is required to treat DM; (3) the global economic cost spent for diabetes treatment in 2014 was little more than 600 billion US dollars, there is an urgent need to find: (i) a way to induce regeneration of adult ß-cells that were lost in DM; (ii) a cheaper alternative to the existing expensive weight-loss drugs; (iii) a side-effect-free natural product-based drug; and (iv) a way to cure, not just treat, diabetes.
What is known?
Prof. Yuval Dor’s research team has recently shown that deletion of Pax6 in mice results in: (1) Hyperglycemia; (2) Ketosis (higher levels of 3-hydroxybutyrate and acetoacetate); (3) down regulation of Mafa, Insulin, Nkx6.1, Pdx1, Isl1, Foxa2, Slc2a2 (GLUT2), G6pc2, and Slc30a8; (4) up regulation of glucagon, somatostatin, ghrelin, Neurog, gastrin, and pancreatic polypeptide; (5) loss of ß cell differentiation and function and (6) expansion of α-cells. Further, they have shown that: (1) Pax6 increases the expression of insulin; (2) Pax6 decreases the expression of islet cell genes, such as ghrelin, glucagon, somatostatin, FOXA2, and Neurog3; (3) Pax6 is down regulated in ß cell of diabetic mice; and (4) Pax6’s function is preserved in human in ß cells, suggesting that increasing the expression of Pax6 in diabetic patients may alleviate TIIDM.
From research findings to Therapeutic opportunity:
This study suggests an artificial sweetener-based therapy for diabetes. Trehalose, by increasing the expression of its target gene, it may increase the expression of Pax6 (fig.1). Thereby, it may: (1) increase insulin sensitivity; (2) inhibit the expression of islet cell genes, including glucagon, ghrelin and Somatostatin; (3) increase the expression of Mafa, Insulin, Nkx6.1, Pdx1, Isl1, Foxa2; (4) decrease metabolic stress; and (5) promote glucose homeostasis (Fig.1). Thus, pharmacological formulations encompassing “Trehalose or its analogues, either alone or in combination with other drugs,” may be used to treat TIIDM.
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How does Agavin increase the expression of Pax6?
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Citation: Boominathan, L., A sweet way to stay free of TIIDM: Trehalose, a disaccharide and artificial sweetener found in mushroom and others, increases Pax6 and insulin expression, decreases the levels of glucagon, ghrelin and Somatostatin, reduces metabolic stress, improves insulin sensitivity, promotes glucose homeostasis and prevents progression to TIIDM via down regulation of its target gene, 26/May/2019, 11.48 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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