Molecular therapy for TIIDM and Metabolic defects: AP-1 (Activator protein-1) increases Sirtuin-4 expression, augments insulin secretion, reduces metabolic stress, improves glucose uptake, promotes glucose homeostasis and prevents progression to TIIDM via down regulation of its target gene, 20/December/2018, 9.59 pm

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Introduction: What they say

A study from the “Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27701, USA; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, NC 27710, USA” shows that “SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion.” This research paper was published, in the 4 April 2017 issue of the journal “Cell Metabolism” [One of the best research journals in Metabolism with an I.F of 28 plus], by Prof. Hirschey MD and Anderson KA 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 TIIDM and Metabolic defects: AP-1 (Activator protein-1) increases Sirtuin-4 expression, augments insulin secretion, reduces metabolic stress, improves glucose uptake, 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. Hirschey research team has recently shown that Loss of Sirtuin-4 in mice results in:(1) dysregulated leucine metabolism; (2) abnormal insulin secretion; (3) glucose intolerance; and (4) accelerated-age induced insulin resistance, suggesting that increasing the expression of Sirtuin-4 in diabetic and obese patients may alleviate TIIDM and metabolic defects.


From Research findings to Therapeutic opportunity:

This study suggests that Activator protein-1 (AP-1), consisting of mainly c-Jun and c-fos and other AP-1 family proteins,  may aid in the treatment of TIIDM and metabolic defects. AP-1, by increasing the expression of its target gene, it may increase the expression of Sirtuin-4. Thereby, it may: (1) normalize leucine metabolism; (2) promote insulin secretion; (3) promote glucose homeostasis during ageing; and (4) decrease metabolic stress (Fig.1).

Figure 1. Mechanistic insights into how Activator protein-1 (AP-1) functions as an antihyperglycemic agent. AP-1, by increasing the expression of Sirtuin-4, it may normalize leucine metabolism and promote insulin secretion.

Figure 2. AP-1 functions as an anti-hyperglycemic agent.

Thus, pharmacological formulations encompassing “AP-1 activators, either alone or in combination with other drugs,” may be used to promote glucose homeostasis and treat TIIDM.


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 AP-1 increase the expression of Sirtuin-4?

Amount: $500#

# Research coperation

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 TIIDM and Metabolic defects: AP-1 (Activator protein-1) increases Sirtuin-4 expression, augments insulin secretion, reduces metabolic stress, improves glucose uptake, promotes glucose homeostasis and prevents progression to TIIDM via down regulation of its target gene, 20/December/2018, 9.58 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

Courtesy: When you cite, drop us a line at info@genomediscovery.org

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