Curing, preventing and reversing diabetes with a commonly available blood pressure drug Hydralazine: Hydralazine-based therapy for TIIDM and obesity-associated metabolic deficits: Hydralazine (trade name: Apresoline, BiDil, and others), a vasodilator used in the treatment of high blood pressure,  cardiac failure and others, increases Lipocalin 2 (LCN2) expression, activates an MC4R-dependent anorexigenic pathway, decreases TXNIP expression, suppresses appetite and weight gain, increases insulin secretion, improves glucose tolerance, promotes glucose homeostasis, improves obesity-associated metabolic deficits and prevents progression to TIIDM, via down-regulation of its target gene, 14/November/2019, 9.58 am

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Introduction: What they say

A study from the Department of Physiology-Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York, USA shows that “MC4R-dependent suppression of appetite by bone-derived lipocalin 2.” This research paper was published, in the 8 March 2017 issue of the journal “Nature” [One of the best research journals in General Science with an I.F of 43 plus], by Dr. Stavroula Kousteni and Mosialou and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhDDirector-cum-chief Scientist of GBMD, reports that:  Curing, preventing and reversing diabetes with a commonly available blood pressure drug Hydralazine: Hydralazine-based therapy for TIIDM and obesity-associated metabolic deficits: Hydralazine (trade name: Apresoline, BiDil, and others), a vasodilator used in the treatment of high blood pressure,  cardiac failure and others, increases Lipocalin 2 (LCN2) expression, activates an MC4R-dependent anorexigenic pathway, decreases TXNIP expression, suppresses appetite and weight gain, increases insulin secretion, improves glucose tolerance, promotes glucose homeostasis, improves obesity-associated metabolic deficits 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) diabetic disease results in a number of health complications, including diabetic cardiomyopathy (DCM), 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) Obesity plays a central role in the development of TIIDM; (5) Diabetes is going to be one of the top 10 causes of death by 2030; (6) the life-long painful injection/drug treatment is required to treat DM; (7) 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?

Dr. Stavroula Kousteni’s research team has recently shown, using loss-and gain-of-function experiments, that Lipocalin 2 (LCN2): (1) induces insulin release; (2) improves glucose tolerance; and (3) augments insulin sensitivity. Further, they have shown that LCN2: (1) binds and activates the melanocortin 4 receptor (MC4R) in the neurons of the hypothalamus; (2) activates an MC4R-dependent appetite-suppressing pathway; (3) suppresses appetite and body weight gain; (4) levels are low in TIIDM patients and they are inversely correlated with body weight gain and blood A1c levels; and (5) levels are higher in patients with lower body weight gain and blood A1c levels, suggesting that increasing the expression of LCN2 may alleviate metabolic deficits in diabetic patients.


From research findings to Therapeutic opportunity:

This study suggests, for the first time, that anti-hypertensive drug Hydralazine (trade name: Apresoline, BiDil, and others), a vasodilator used in the treatment of high blood pressure,  cardiac failure and others, may aid in the treatment of weight loss and obesity-associated TIIDM.

Hydralazine, by increasing the expression of its target gene, it may increase the expression of LCN2 (Lipocalin 2). Thereby, it may: (1) induce insulin release; (2) increase the expression of components of the Insulin-PI3K pathway; (3) promote glucose tolerance; (4) improve insulin sensitivity; (5) activate the MC4R (Melanocortin-4-receptor-MC4R)-dependent appetite-suppressing pathway in hypothalamus; (6) decrease Thioredoxin-interacting protein (TXNIP) expression; (7) suppress appetite; and weight gain; (8) improve metabolic deficits; and (9) promote glucose homeostasis (Fig.1).

Figure 1. Mechanistic insights into how blood pressure drug verapamil suppresses appetite, promotes insulin secretion, and attenuates the development of Type II diabetes mellitus & obesity-associated metabolic abnormalities.

Figure 2. Anti-hypertensive drug verapamil may alleviate blood sugar levels by upregulating the expression of MC4R (Melanocortin 4 receptor-MC4R)

Figure 3. While it had been shown earlier that Verapamil improves beta cell function in adults with recent-onset type 1 diabetes, its mechanism of action remains largely unclear. This study suggests that how anti-hypertensive drugs verapamil and Hydralazine may alleviate blood sugar levels by upregulating the expression of MC4R (Melanocortin 4 receptor-MC4R), while down regulating the expression of TXNIP.

Given the detailed mechanistic basis as to how anti-hypertensive drug Hydralazine may decrease blood glucose levels, medical practitioners/diabetologists may consider taking this interesting finding into a clinical trial or adopting this as a mode of therapy for diabetes mellitus and Obesity-associated metabolic deficits/abnormalities (Figure 2), as this drug has an added advantage of promoting stress resistance and functioning as a longevity-promoter in worms.


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 Hydralazine increase the expression of LCN2 and MC4R and down regulate the expression of TXNIP?

Amount: $1, 500#

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

# Research cooperation


References:

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

Citation: Boominathan, L., Curing, preventing and reversing diabetes with a commonly available blood pressure drug Hydralazine: Hydralazine-based therapy for TIIDM and obesity-associated metabolic deficits: Hydralazine (trade name: Apresoline, BiDil, and others), a vasodilator used in the treatment of high blood pressure,  cardiac failure and others, increases Lipocalin 2 (LCN2) expression, activates an MC4R-dependent anorexigenic pathway, decreases TXNIP expression, suppresses appetite and weight gain, increases insulin secretion, improves glucose tolerance, promotes glucose homeostasis, improves obesity-associated metabolic deficits and prevents progression to TIIDM, via down-regulation of its target gene, 14/November/2019, 9.58 am, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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

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