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: Mechanistic insights into how Liraglutide aids in remission of Diabetes: Liraglutide (brand name: Victoza, Saxenda and others), a drug used in the treatment of type II diabetes, 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:
I had suggested earlier (on 14/November/2017 at 5.14 am and in others) that how Victoza/Saxenda/Liraglutide (a GLP-1 analogue) may improve insulin sensitivity and protect against obesity and diabetes (https://genomediscovery.org/2017/11/molecular-therapy-for-tiidm-and-obesity-associated-metabolic-deficits-victozasaxenda-a-drug-used-in-the-treatment-of-tiidm-and-obesity-increases-lipocalin-2-lcn2-expression-activates/; and https://genomediscovery.org/2019/05/mechanistic-insights-into-how-liraglutide-aids-in-control-of-body-weight-energy-homeostasis-and-tiidm-liraglutide-brand-name-victoza-saxenda-and-others-a-drug-used-in-the-t/ ).
Evidently, a very recent study from the Department of Pediatrics, Yale University, New Haven, CT; Pediatric Endocrinology, Angeles Hospital of Puebla, Puebla City, Mexico; Novo Nordisk, Søborg, Denmark; the Diabetes and Endocrinology Unit, Department of Paediatrics, Cairo University, Cairo; Novo Nordisk, Plainsboro, NJ; Institute of Cancer and Genomic Sciences, University of Birmingham,and Birmingham Women’s and Children’s Hospital, Birmingham, United Kingdom and others shows that “Liraglutide in Children and Adolescents with Type 2 Diabetes.” This study was published, in the 28 April 2019 issue of of the prestigious journal N Engl J Med. (NEJM) (Impact factor: 79.258+), by Prof. Timothy Barrett, Tamborlane and others. This study suggests that Liraglutide, in conjunction with Metformin, is efficacious in improving glycemic control in children and adolescents with type II diabetes. However, the precise mechanism of action of this drug remains largely unclear.
This study substantiates their claim by providing a detailed mechanistic insights into how Liraglutide may aid in attenuating insulin resistance and in the treatment of weight loss and obesity-associated TIIDM.
Liraglutide, 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 (Figs.1-2).
Thus, pharmacological formulations encompassing “Liraglutide or its analogs, either alone or in combination with other drugs,” may be used to treat TIIDM (Fig.3).
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/
Undisclosed mechanistic information: How does Liraglutide increase the expression of Pax6?
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Citation: Boominathan, L., Mechanistic insights into how Liraglutide aids in remission of Diabetes: Liraglutide (brand name: Victoza, Saxenda and others), a drug used in the treatment of type II diabetes, 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, 20/June/2019, 11.14 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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