Breakthrough study: Eating this bitter fruit for rockiness

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[Click here to discover this strange seduction technique right now.]( ---------- Breakthrough study: Eating this bitter fruit for “rockiness” Men with blood sugar problems have difficulties in the bedroom. Even “pre diabetic” men are experiencing huge problems with their wives or girlfriends. And now comes an Asian breakthrough that increases male blood flow and also helps blood sugar. Let me explain. Throughout human history, certain plants have empirically become known as effective antidiabetic agents. Scientific tests shows that these plants really DO work. Bitter melon is one such plant. Along with ginseng, banabá leaf, olive leaf, and Cornelian cherry, a full understanding of these plants' effects had to wait until the recent discovery (Maruyama, 2002) of the TGR5 receptor. This is because TGR5 is the cell membrane receptor for bile salts, and is now considered an antidiabetic target. All of the aforementioned plants contain tri‑terpene ligands known to activate TGR5, all in low concentrations: Stimulation of TGR5 has been shown to release insulin from pancreatic beta‑cells (Kumar, 2012), increase glucose uptake in the muscle (Tan, 2008), and enhance thyroid hormone activation in adipose tissue (Watanabe, 2006). The manifold effects claimed of TGR5 can sound almost unbelievable, but they all derive from just one second messenger: cyclic‑AMP. The TGR5 receptor is linked to an anchoring enzyme called Gas on the cell membrane, a G‑protein adenylate cyclase known to synthesize cyclic‑AMP. Catecholamines (e.g. adrenaline, noradrenaline) and adenosine analogues (e.g. caffeine, theophylline) are also linked to Gas. And, as such, they both exert similar effects in cells expressing their receptors. This bile salt receptor is expressed in many organs, including the brain and thyroid. That might seem bizarre but, in fact, bile salts are found in the bloodstream. Bile salts are effectively absorbed. And their concentrations in the plasma increase three‑fold after eating. “Fasting serum BA levels are usually lower than 5 μM, whereas postprandial levels increase to up to 15 μM…” So, besides aiding digestion in the intestine through their physico‑chemical properties, the same bile salts then become a signal for glucose upon reaching the plasma. So its peripheral effects can be understood teleologically for this reason… They act somewhat as a fundamental proto‑insulin that arose earlier in our evolution. The effects of bile salts are also similar to thyroid hormone… Though this likely came about later in evolution because it depends on type‑2 deiodinase induction. So here's the evidence that the triterpenoids in bitter melon are antidiabetic and prometabolic substances, and also that they act on TGR5: As the title of the study suggests, this study analyzed the effects of bitter melon triterpenoids on muscle cells. The researchers isolated ten triterpenoids in total, all structurally similar and capable of “activating AMPK” and increasing GLUT4 translocation. While some were barely active, two in particular were surprisingly potent in inducing glucose uptake. Most of these triterpenoids, notably compounds 4 and 8, were the very same ones isolated earlier and presumed responsible for bitter melon's effects. And, as in the previous study, these researchers confirmed the hypoglycemic effects of these compounds in living rats. A few of them were even effective in the nanomolar range, meaning their effects would be expected after ingesting bitter melon fruit and extracts. “The dose-response curves showed that compounds 1, 4, 5, and 8 exhibited this biological activity at concentrations as low as 0.1 nM and reached their maximal effects at between 10 and 100 nM.” So these triterpenoids are nearly as potent as the hormone insulin, though definitely not acting through insulin receptors. On account of their activity not being blocked by wortmannin, a classic inhibitor of insulin signaling, there must be some other cellular target responsible for their effects. Unfortunately, this study did not determine exactly where the triterpenoids were acting. However, based on their structural similarity to bile salts and other TGR5 ligands, we can probably infer where they do act. Although bile salts also have a nuclear receptor called farnesoid‑X receptor (FXR), shown to transcribe for GLUT4, this cannot be responsible here because it is not expressed in skeletal muscle. For this reason, TGR5 seems a more likely target for the triterpenoids in bitter melon. It has been shown that a significant fraction of glucose transporters resides in the cytosol, and then repartitions towards the membrane after becoming phosphorylated. It's fair to assume TGR5 can do this since it's been shown to activate kinase enzymes, or phosphotransferases. And that probably occurs through increasing cyclic‑AMP. But, in addition to that study, there's more on bitter melon, all demonstrating its antidiabetic effects and pointing towards TGR5: As the title of this study suggests, the bitter melon fruit (also known as the bitter gourd) could have something to do with GLP‑1 signaling. Glucagon-like peptide‑1 (GLP‑1) is a hormone released by endocrine cells in the intestines. That hormone then travels through the portal vein towards the liver and pancreas. After reaching the pancreas, GLP‑1 stimulates insulin release from beta‑cells in very low concentrations. Incidentally, GLP-1 is rapidly degraded by dipeptidyl peptidase‑IV (DPP‑IV) in the bloodstream. So its effects are short-lived. The ability of GLP‑1 to release insulin has made it a prime target in treating diabetes. This is also the reason why DPP‑IV inhibitors are often prescribed in doing so. So, on account of bitter melon's known antidiabetic effects, and the foregoing considerations about GLP‑1, these researchers decided to investigate the fruit further. So they tested different bitter melon extracts on GLP‑1 release from STC‑1 cells, an intestinal endocrine cell line. Upon finding a potent response from the water extract, they continued their line of inquiry. And like the two bitter melon studies mentioned previously, these researchers reduced its effects down to a handful of triterpenoids… And two of them were quite potent: The effective concentrations were higher than the ones necessary for GLUT4 translocation in muscle cells… But the intestine is naturally exposed to much higher concentrations of bile salts simply when we eat. Lithocholic acid – a natural bile salt – has been shown to double GLP‑1 release from the same cell line at 30 μM. This indicates that compound 5 is nearly equipotent as it requires 50 μM to do the same. They showed that dried bitter gourd powder at 5% of diet significantly lowered blood glucose in mice. They also showed that this effect could be largely blocked by exendin‑9, a potent GLP‑1 receptor antagonist… This suggests that bitter melon doesn't work merely by decreasing glucose absorption. “Thus, these data indicate that the cucurbitane triterpenoids are significantly more potent in vivo than a traditional AMPK agonist.” So the antidiabetic effects of bitter melon have been scientifically validated many times over, and could only occur through TGR5. The release of GLP‑1 is a demonstrated effect of TGR5 activation. And other plant compounds known for antidiabetic activity have been shown to potently activate it. Although it's true that many natural TGR5 ligands have been shown to have other antidiabetic targets, such as 11beta‑HSD1 and PTP‑1B, you could suppose that they all release GLP‑1 upon absorption. This would mean that ginseng, banabá leaf, olive leaf, and Cornelian cherry should be taken with food to better time the insulin–GLP‑1 increase with glucose intake. It's easy to imagine that simply taking bile salts themselves would be more effective… But maybe not, since they also activate the farnesoid‑X receptor. Although this receptor has been shown to induce GLUT4 transcription and glucose uptake, it can also downregulate GLP‑1 production. These could seem a somewhat paradoxical effect of bile salts. But it could simply be a homeostatic mechanism to keep GLP‑1 signaling in range. Natural bile acids release GLP‑1 through TGR5 receptors on the cell's membrane. Yet should enough get inside, the basal GLP‑1 production would decrease somewhat through the farnesoid‑X receptor (FXR). This is similar to how bile acids inhibit their own production, a safeguard that keeps their concentrations within a reasonable range. “Bile acid concentrations are controlled by a feedback regulatory pathway whereby activation of the farnesoid-X receptor represses transcription of both the CYP7A1 gene, encoding the rate-limiting enzyme in the classic bile acid synthesis pathway ... and the CYP8B1 gene, required for synthesis of cholic acid.” So although supplemental bile salts should be safe and effective, they could also create dependency by downregulating endogenous production. This would mean that you would have to take bile salts with every meal or else digestion would suffer as a consequence of low bile output. On the other hand, supplements containing natural plant compounds that act exclusively on TGR5 are immune to this problem. Taking these would allow for greater freedom, allowing a person to go without them during extenuating circumstances. ----Important Message---- A youthful metabolism creates massive wood -- here’s how to achieve it Remember being 15 years old and eating two helpings at every meal? And I’ll bet your member was always sproinging to attention too... You never gained a pound of fat eating this way...and you were ready for action if you ever got lucky with a girl (I never did, LOL)... In fact, you burned calories just sitting still. You had crazy energy. It’s not like that anymore, is it? So why is that? What’s the difference between then and now? Metabolism. As we age, it slows down. If we could just speed it up again, our testosterone would jump high again, and we’d have those youthful “rocky” ones --- but this time we’d know what to do with it, LOL. So now you know why I spent years researching a way to speed up my own metabolism. I tried many, many things. And nothing worked...until I found a combination of ingredients that naturally restore a teenage metabolism. It works for me, and I’m almost 60. I plan to use it when I’m 110 years old. I believe that it will help me live decades longer. Did you know that a fast metabolism can extend lifespan? And makes sex SO much better... [You won’t believe this story, but I swear under penalty of perjury it’s true…]( ---------- Daily Medical Discoveries is dedicated to uncovering secret, buried or censored studies that can help men live great lives to 120 and beyond. You are subscribed because you joined one of our lists by opting in. We never rent or share your email address. Daily Medical Discoveries is published by Calworth Glenford LLC which also publishes other affiliated companies. By giving us your email address, you consent for Daily Medical Discoveries and its affiliated companies to delivering you a healthy daily portion of email issues and advertisements. 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