Molecular therapy for Diabetes Mellitus: Canagliflozin(trade name Invokana or Sulisent), a sodium-glucose cotransporter-2 inhibitor used in the treatment of TIIDM, augments the expression of FGF19 and FGF1,  attenuates hepatic glucose production, decreases hepatic acetyl CoA content, brings down the levels of plasma ACTH, and corticosterone, augments insulin sensitivity, promotes weight loss and alleviates TIDM via upregulation of its target gene, 18/February/2019, 1.00 pm

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Introduction: What they say 

A study from Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, Washington, USA shows that Central injection of FGF1 induces sustained remission of diabetic hyperglycemia in rodents. This research paper was published, in the 23 May 2016 issue of the journal “Nature Medicine” [One of the best research journals in General Medicine with an I.F of 29.886 plus], by Prof. Schwartz MW and Scarlett JM and others.

Another study from Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536-8012, USA; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-8012, USA; and Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06536-8012, USA shows that “FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic-pituitary-adrenal axis.” This research paper was published, in the 28 April 2015 issue of the journal “Nature communications” [One of the best research journals in General science research with an I.F of 11.329 plus], by Prof. Shulman GI and Perry RJ and others.

Yet another study from Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037, USA shows that “Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer.” This research paper was published, in the 16 July 2014 issue of the journal “Nature” [One of the best research journals in General science with an I.F of 43 plus], by Prof. Evans RM and Suh JM and others


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Molecular therapy for Diabetes Mellitus: Canagliflozin(trade name Invokana or Sulisent), a sodium glucose cotransporter-2 inhibitor used in the treatment of TIIDM, augments the expression of FGF19 and FGF1,  attenuates hepatic glucose production, decreases hepatic acetyl CoA content, brings down the levels of plasma ACTH, and corticosterone, augments insulin sensitivity, promotes weight loss and alleviates TIDM via upregulation of its target gene


From significance of the study to public health relevance:

Given that: (1) more than 422 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. Shulman GI’s research team has shown that injection of FGF19 or FGF1:(1) decreases hepatic glucose production and hepatic acetyl CoA content by 60%; (2) promote  whole-body lipolysis; (3) lowers plasma ACTH, and corticosterone concentrations; and (4) has no glucose-lowering effect when it is countered with intra-arterial infusion of corticosterone, suggesting that increasing the expression of FGF19 or FGF1 in diabetic patients may decrease insulin resistance, and alleviate TIDM.


From research findings to Therapeutic opportunity:

Canagliflozinby increasing the expression of its target genes, it may increase the expression of FGF19 or FGF1/2. Thereby, it may: (1) inhibit hepatic glucose production; (2) decrease hepatic acetyl CoA content; (3) increase insulin sensitivity, beta-cell self-renewal and regeneration; (4) augment lipolysis and weight loss; (5) protect against diet-induced obesity; (6) protect against development of TIDM (Fig.1).

Figure 1. Mechanistic insights into how Canagliflozin increases the expression of FGF19 and FGF1/2 and promotes insulin sensitivity and weight loss

Figure 2. Canagliflozin increases the expression of FGF19 and FGF1/2 and promotes insulin sensitivity and weight loss.

Thus, pharmacological formulations encompassing “Canagliflozin  or its analogs, either alone or in combination with other drugs,” may be used to treat DM patients.


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 Canagliflozin  increase the expression of FGF19 or FGF1/2?

Amount: $ 500#

# Research cooperation

For purchase and payment details, you may reach us at info@genomediscovery.org


References:

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L.,  Molecular therapy for Diabetes Mellitus: Canagliflozin (trade name Invokana or Sulisent), a sodium glucose cotransporter-2 inhibitor used in the treatment of TIIDM, augments the expression of FGF19 and FGF1,  attenuates hepatic glucose production, decreases hepatic acetyl CoA content, brings down the levels of plasma ACTH, and corticosterone, augments insulin sensitivity, promotes weight loss and alleviates TIDM via upregulation of its target gene, 18/February/2019, 1.00 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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