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Combination (Amino acid + Polyamine) therapy for reversing TIIDM: A pharmaceutical mixture encompassing  L-Arginine and Spermidine 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 TIIDM, via up regulation of its target gene, 8/March/2018, 6.55 am

Amino acid-based therapy for body weight control, energy homeostasis and TIIDM: L-Arginine, a non-essential amino acid that aids in blood flow and in maintaining optimal nitric oxide levels, increases REV-ERB and its down stream target genes, inhibits lipid accumulation, improves dyslipidemia and insulin sensitivity, increases energy utilization, promotes weight loss and protects from diet-induced obesity and TIIDM, via up regulation of its target gene, 8/March/2018, 6.36 am
March 8, 2018
Small-molecule based therapy for reversing autoimmune diabetes (TIDM): Lactoferrin, a globular glycoprotein commonly found in secretory fluids, increases PD-L1 expression, increases Tregs function, promotes immune tolerance, increases pancreatic β-cell proliferation and regeneration, increases insulin secretion, improves insulin sensitivity, increases energy utilization, and reverses TIDM, via up regulation of its target gene, 8/March/2018, 7.06 am
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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: Combination (Amino acid + Polyamine) therapy for reversing TIIDM: A pharmaceutical mixture encompassing  L-Arginine and Spermidine 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 TIIDM via up regulation 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:

This study suggests, for the first time, a combinatorial therapy for DM patients. A number of studies suggests that L-Arginine may aid in promoting blood flow and in maintaining nitric oxide levels, while polyamine Spermidine may aid in promoting cardioprotection and extending lifespan.  A pharmaceutical mixture encompassing  L-Arginine and Spermidineby 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 TIIDM (Fig.1).

Figure 1. Mechanistic insights into how a pharmaceutical mixture encompassing  L-Arginine and Spermidine increases the expression of FGF19 and FGF1/2 to promote insulin sensitivity and weight loss

Figure 2. The chemical structure of L-Arginine and Spermidine.  A pharmaceutical mixture  encompassing L-Arginine and Spermidine increases the expression of FGF19 and FGF1/2 to promote insulin sensitivity and weight loss. Of relevance, L-Arginine and Spermidine share a structural similarity with Metformin, the widely prescribed drug in the treatment of TIIDM.

Thus, pharmacological formulations encompassingL-Arginine and Spermidine or their analogues, 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 a pharmaceutical mixture encompassing  L-Arginine and Spermidine increase the expression of FGF19 or FGF1/2 to promote insulin sensitivity and weight loss?

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.,  Combination (Amino acid + Polyamine) therapy for reversing TIIDM: A pharmaceutical mixture encompassing  L-Arginine and Spermidine 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 TIIDM via up regulation of its target gene, 8/March/2018, 6.55 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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