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Introduction: What they say 

Nobel laureate [ in Physiology/Medicine in 1975] Prof. David Baltimore and his research team, from California Institute of Technology, California, USA, had reported in the September 14, 2014 issue of the Journal “Journal of Experimental Medicine (JEM)” that: The microRNA-212/132 cluster regulates B cell development by targeting Sox4.”

Subsequently, Prof. Rorsman’s research team, from Oxford Centre for Diabetes, Endocrinology & Metabolism, Radcliffe Department of Medicine, Oxford, U.K; Department of Neuroscience and Physiology, University of Göteborg, Göteborg, Sweden Oxford; and National Institute of Health Research, Biomedical Research Centre, Churchill Hospital, Oxford, U.K, had reported, in the March 18, 2016 issue of the Journal “Diabetes”, that Increased Expression of the Diabetes Gene SOX4 Reduces Insulin Secretion by Impaired Fusion Pore Expansion.”


What we say:

On the foundation of these interesting findings, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Mechanistic insights into how Liraglutide aids in remission of hyperglycemia: Liraglutide (brand name: Victoza, Saxenda and others), a  drug used in the treatment of type II diabetes, inhibits Amysin expression, increases insulin secretion, and decreases the risk of hyperglycemia, via downregulation of  Sox4 and its target gene Amysin

price-300


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.


From what is known to what we infer from what they say:

Prof. Rorsman’s research team has recently shown that overexpression of Sox4 results in: (1) increased expression of Amysin; (2) reduction in fusion pore size; (3) impairment of granule emptying; (4) impairment of insulin exit; (5) prevention of hormone release; and (6) reduction of glucose-induced insulin secretion, suggesting that decreasing the expression of Sox4 and its target gene Amysin in diabetic patients may alleviate TIIDM.

[easy_payment currency=”USD”]


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 genes, it may: (a) decrease the expression of exocytosis-regulating protein SOX4 and its target gene Amysin; (b) decrease the expresison of TXNIP; and (c) increase the expression of PPARγ2 and A-FABP (fig.1). Thereby, it may: (1) promote granule emptying and insulin release; and (2) increase glucose-induced-insulin secretion.

Figure1. Mechanistic insight into how Liraglutide promotes insulin secretion. Liraglutide inhibits weight gain, insulin resistance, myocardial infarction, and cardiac ageing, through down-regulation of Sox4 and its target gene Amysin

Figure 2.  Liraglutide inhibits weight gain, and insulin resistance, through down regulation of Sox4 and its target gene amysin.

Figure 3. Liraglutide, by suppressing the expression of SOX4 and TXNIP, aids in control or remission of diabetes

Together, this study suggests provides mechanistic insights into how Liraglutide aids in control or remission of diabetes.


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 decrease the expression of Sox4/Amysin?

Amount: $300#

# 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.,  Mechanistic insights into how Liraglutide aids in remission of hyperglycemia: Liraglutide (brand name: Victoza, Saxenda and others), a  drug used in the treatment of type II diabetes, inhibits Amysin expression, increases insulin secretion, and decreases the risk of hyperglycemia via down regulation of  Sox4 and its target gene Amysin,  20/June/2019, 7.14 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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