Introduction: What they say
A study from the Institute for Molecular Systems Biology, ETH Zurich, Zurich, Switzerland shows that “MicroRNAs 103 and 107 regulate insulin sensitivity.” This study was published, in the June 8, 2011 Nature [One of the best journals in Science with an I.F of >43], by Prof. Stoffel M, Trajkovski M and others.
In connection to the above finding, Prof. Irani K’s research team, from Cardiovascular Division, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, USA; University of California, San Diego, USA; and VA San Diego Healthcare System, University of California, San Diego, USA had reported in the February 9, 2016 issue of the Journal “Scientific Reports” that “Sirtuin1 protects endothelial Caveolin-1 expression and preserves endothelial function via suppressing miR-204 and endoplasmic reticulum stress.”
What we say:
On the foundation of these interesting findings, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Molecular therapy for Metabolic diseases: Victoza/Saxenda, a glucagon-like peptide-1 receptor agonist that promotes insulin secretion, increases the expression of Caveolin-1, stabilizes insulin receptor, promotes insulin sensitivity, incrases vasorelaxation, and decreases the risk of hyperglycemia and TIIDM via up 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) diabetic disease results in a number of health complications, including diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy; (3) one third of people with diabetes suffer from diabetic kidney disease (DKD); and one third of them will develop kidney failure; (4) Diabetes is going to be one of the top 10 causes of death by 2030; (5) the life-long painful injection/drug treatment is required to treat DM; (6) 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. Stoffel’s research team had shown that inactivation of MiR-103/107 results in (1) increased expression of Caveolin-1; (2) Stabilization of the insulin receptor; (3) enhanced insulin-signalling and -sensitivity; (4) reduced adipocyte size; and (5) enhanced glucose-induced insulin secretion. Further, they have shown that miR-103/107 is upregulated in obese mice, suggesting that decreasing the expression of MiR-103/107 may increase the expression of Caveolin-1 (CAV1) in diabetic patients and alleviate TIIDM.
In line with above findings, Prof. Irani’s research team had shown that deletion of endothelial Sirtuin1 in mice results in (1) increased ER stress; (2) increased miR-204 expression; (3) reduction of Caveolin-1 expression; and (4) impaired endothelium-dependent vasorelaxation. Further, they have shown that inhibition of miR-204 results in (1) up regulation of Caveolin-1; and (2) inhibition of vascular ER stress, suggesting that increasing the expression of Sirtuin1 may increase and decrease the expression of Caveolin-1 (CAV1) and miR-204, respectively, in diabetic patients, and alleviate TIIDM.
From research findings to therapeutic opportunity:
Liraglutide (marketed as Victoza/Saxenda), a glucagon-like peptide-1 receptor agonist, has been shown to promote insulin secretion.
This study provides provides, for the first time, mechanistic insights into how Liraglutide may promote insulin sensitivity, vasorelaxation and leanness.
Liraglutide, by increasing the expression of its target genes, it may increase the expression of Caveolin-1 (CAV-1) (fig.1).
Thereby, it may: (1) promote stabilization of insulin receptor; (2) enhance insulin signalling; (3) increase insulin sensitivity; (4) decrease miR-204 expression; (5) attenuate ER stress; and (6) promote vasorelaxation. Thus, pharmacological formulations encompassing “Liraglutide or its analogues, either alone or in combination with other drugs,” may be used to treat TIIDM and its associated vascular complications.
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 Victoza/Saxenda increase the expression of Caveolin-1 to promote insulin sensitivity?
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Citation: Boominathan, L., Molecular therapy for Metabolic diseases: Victoza/Saxenda, a glucagon-like peptide-1 receptor agonist that promotes insulin secretion, increases the expression of Caveolin-1, stabilizes insulin receptor, promotes insulin sensitivity, incrases vasorelaxation, and decreases the risk of hyperglycemia and TIIDM via up regulation of its target gene, 14/November/2017, 6.23 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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