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Research Chemical SciencesUGFREAKeudomestic
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More glp1 the future to extreme muscle mass

DarrenW29

New member
Dulaglutide improved muscle strength and attenuated muscle loss in disuse condition. Ten-week-old C57BL/6 male mice were subjected to spiral wire immobilization for 4 d and administrated dulaglutide (Trulicity, 600 µg/kg, subscutaneous). Mice were maintained for additional 7 d. (A) Grip strength was measured on day 11 and grip strength value was normalized to final body weight. (B) Body weights on day 0 and 11 were recorded. (C) The total muscle weight and weight of various muscle types, including gastrocnemius (GA), soleus, tibialis anterior (TA), extensor digitorum longus (EDL), and quadriceps (QD), were measured right after sacrifice and normalized to the final body weight. Data are shown as means ± S.E.M, n = 6–7/group; *p < 0.05, **p < 0.01, ***p < 0.001. CV, control + vehicle; CD, control + dulaglutide; IV, immobilization + vehicle, ID; immobilization + dulaglutide.

Dulaglutide treatment increased muscle fiber size in disuse-induced skeletal muscle atrophy. (A) GA muscle tissue sections were stained with H&E and examined under microscope. (B) The cross-sectional area (CSA) of muscle fiber was measured using ImageJ program and the average CSA is shown. (C) Distribution of myofiber size. Data are shown as means ± S.E.M, n = 5; *p < 0.05, **p < 0.01, ***p < 0.001 versus control + vehicle or immobilization + vehicle group. CV, control + vehicle; CD, control + dulaglutide; IV, immobilization + vehicle; ID, immobilization + dulaglutide.

Dulaglutide treatment decreased the mRNA and protein expression levels of degradation-related genes under disuse-induced muscle atrophy. (A) The mRNA levels of the genes encoding MuRF-1, atrogin-1, and myostatin were analyzed with RT-qPCR in GA muscle tissue, n = 5. GAPDH mRNA served as an internal control. (B) Immunoblotting and (C) quantification analyses of MuRF-1, atrogin-1, and myostatin protein expression in GA muscle. Beta-actin was used as a loading control to ensure equal protein loading, n = 3. (D) The mRNA expression of myosin heavy chain isoforms, including myosin heavy chain type I, type IIa, and type IIb, was evaluated with RT-qPCR, n = 5. GAPDH mRNA was used as an internal control. (E) Immunoblotting and (F) quantification analyses of myosin heavy chain protein expression in GA muscle. Beta-actin was used as a loading control, n = 5. Data are shown as mean ± S.E.M. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with control + vehicle or immobilization + vehicle group. CV, control + vehicle; CD, control + dulaglutide; IV, immobilization + vehicle; ID, immobilization + dulaglutide.

Dulaglutide treatment reduced the expression of proinflammatory cytokines and p50 NF-κB in disuse-induced muscle atrophy. (A) The mRNA expression levels of TNF-α, IL-1β, and IL-6 were analyzed with RT-qPCR in GA muscle tissue. GAPDH mRNA was used as an internal control. (B) Immunoblotting and (C) quantification analyses of p50 NF-κB and p-IκBα protein expression in GA muscle. Beta-actin was used as a loading control. Data are shown as mean ± S.E.M, n = 5; **p < 0.01 or ***p < 0.001 as compared with control + vehicle or disuse + vehicle group. CV, control + vehicle; CD, control + dulaglutide; IV, immobilization + vehicle; ID, immobilization + dulaglutide.

Dulaglutide prevents apoptosis in disuse condition. (A) Immunoblotting and (B) quantification analyses of caspase-3, cleaved PARP, and Bax proteins in GA muscle. Beta-actin was used as the loading control. Data are showed as mean ± S.E.M, n = 5; *p < 0.05, **p < 0.01, ***p < 0.001. CV, control + vehicle; CD, control + dulaglutide; IV, immobilization + vehicle; ID, immobilization + dulaglutide; ns, not significant.

GLP-1 receptor agonist treatment increased Hsp72 protein expression through the regulation of AMPK signaling. (A) Immunoblotting and (B) quantification analyses of Hsp72 protein expression in GA muscle. (C) Immunoblotting and (D) quantification analyses of Hsp72 protein expression in soleus muscle. Beta-actin was used as a loading control. Data are shown as mean ± S.E.M, n = 5; *p < 0.05, **p < 0.01, ***p < 0.001. CV, control + vehicle; CD, control + dulaglutide; IV, immobilization + vehicle; ID, immobilization + dulaglutide. (E) Immunoblotting and (G) quantification analyses of Hsp72 and p-AMPK proteins in C2C12 myotubes treated with dulaglutide (1.5 µg/ml, 12 h) or Ex-4 (20 nM, 30 min or 3 h). (F) Immunoblotting and (H) quantification analysis of Hsp72 and p-AMPK proteins in C2C12 myotubes pre-treated with compound C at 20 µM for 1 h and then exposed to dulaglutide (1.5 µg/ml, 3 h) or Ex-4 (20 nM, 3 h). Beta-actin was used as the loading control. Data are shown as mean ± S.E.M, n = 3; *p < 0.05, **p < 0.01.

Aside from the blood glucose-lowering effects, GLP-1 receptor agonists also exert beneficial effects on the skeletal muscle by increasing glucose uptake (Thompson and Kanamarlapudi, 2013), fat oxidation, and thermogenic gene expression (Choung et al., 2017). In addition, GLP-1 receptor agonist, Ex-4, imparts therapeutic effects in muscle atrophy induced by dexamethasone (Hong et al., 2019). In the present study, we investigated the effect of dulaglutide, a GLP-1 receptor agonist, on disuse-induced muscle atrophy and evaluated the underlying mechanisms.

Disuse-induced skeletal muscle atrophy is closely related to inflammatory process (Hunter et al., 2002). In addition, GLP-1-based therapies have been shown to exert anti-inflammatory effects in chronic inflammatory diseases (Kim et al., 2017). We evaluated the expression of inflammatory cytokines and found that the mRNA levels of TNF-α, IL-1β, and IL-6 in the GA muscle were upregulated following 10 days from immobilization and that dulaglutide treatment inhibited this increase (Figure 4A). NF-κB activation is important for the induction of inflammatory cytokines, while p50 NF-κB, not p65, is activated during disuse condition (Hunter et al., 2002). IκBα is an inhibitory factor for NF-κB activation (Yamamoto and Gaynor, 2004). We found that p50 NF-κB level increased in immobilized mice while dulaglutide treatment ameliorated this effect. We also examined the expression of p-IκBα, a negative regulator (Yamamoto and Gaynor, 2004), and found that its expression was downregulated in immobilized mice and that dulaglutide treatment restored the levels (Figures 4B, C). These results suggest that GLP-1 receptor agonist may inhibit p-IκBα degradation and decrease p50 NF-κB, thereby contributing to the amelioration of inflammation during disuse conditions in the skeletal muscle.


In conclusion, we demonstrate that treatment with dulaglutide, a GLP-1 receptor agonist, could recover muscle strength, muscle mass, and muscle fiber size, which were reduced during immobilization. Dulaglutide treatment attenuated the induction of atrophic genes, such as those encoding MuRF-1, atrogin-1, and myostatin, and enhanced MHC expression. In addition, dulaglutide treatment inhibited the expression of inflammatory cytokines and apoptotic genes through the induction of heat shock protein 72 (Hsp72) expression via AMPK activation, contributing to the amelioration of disuse-induced muscle atrophy.
 
my question is why would anyone want to get larger and larger unless they were competing or had some sort of mental disorder (bigorexia)?

even if this stuff worked as intended i don't see many people lining up to take it. i'm sure on this forum maybe 10% of guys would be interested which translates to .01% of the population
 
my question is why would anyone want to get larger and larger unless they were competing or had some sort of mental disorder (bigorexia)?

even if this stuff worked as intended i don't see many people lining up to take it. i'm sure on this forum maybe 10% of guys would be interested which translates to .01% of the population

I do plan to compete so this for me is my whole entire life my life revolves around bodybuilding gym there’s absolutely nothing else I do expect eat and train so for me it’s worth it

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And to establish myself more I need to back up what I post with trials on myself and then provide the positives and negatives so far no negatives whatsoever
 
I’m currently on it so I will be able to write more on this 1mg per week so far so good.


Let us know. I would be interested in hearing how it works for you.
 
I do plan to compete so this for me is my whole entire life my life revolves around bodybuilding gym there’s absolutely nothing else I do expect eat and train so for me it’s worth it

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And to establish myself more I need to back up what I post with trials on myself and then provide the positives and negatives so far no negatives whatsoever

2 initial thoughts
1) 4 days atrophy??
2) To make it work you'd need to do nothing.

Another
3) what effect, if any, would it have on actively used muscle. Possibly none.
 
Regarding any myostatin like drugs and or inhibitor blockers:

1) Yes there might be additional muscle. It's worth noting that most drugs aren't tested for that. The 'muscle mice', dogs etc we've seen have usually had gene manipulation.
2) Any and all potential drugs that might have said action are, so far, as likely to cause a whole bunch of side effects. From, for example, heart issues (it being a muscle) to cancer cells being encouraged in their growth.
3) Any growth cannot be site specific - meaning if you have piss poor muscle shape (as in non contest winning) you'd simply be a bigger piss poor shaped version.

Regarding your current status
It WILL change. Keep that in mind. You live for bodybuilding NOW. That can and will change in the future. Every champ still alive has gone on that journey. I say that as someone who will be 57 soon and only this week was throwing around crazy as f**k weights regardless of my old ass lol
 
Regarding any myostatin like drugs and or inhibitor blockers:

1) Yes there might be additional muscle. It's worth noting that most drugs aren't tested for that. The 'muscle mice', dogs etc we've seen have usually had gene manipulation.
2) Any and all potential drugs that might have said action are, so far, as likely to cause a whole bunch of side effects. From, for example, heart issues (it being a muscle) to cancer cells being encouraged in their growth.
3) Any growth cannot be site specific - meaning if you have piss poor muscle shape (as in non contest winning) you'd simply be a bigger piss poor shaped version.

Regarding your current status
It WILL change. Keep that in mind. You live for bodybuilding NOW. That can and will change in the future. Every champ still alive has gone on that journey. I say that as someone who will be 57 soon and only this week was throwing around crazy as f**k weights regardless of my old ass lol

Great post mobster your posts are great and you are a freak and vet so your posts always something I will listen to you are right someday things could change or I might not even make it to 40 but right now I love this but I agree
 
Great post mobster your posts are great and you are a freak and vet so your posts always something I will listen to you are right someday things could change or I might not even make it to 40 but right now I love this but I agree

Cheers fella. A little analysis on my part. Such drugs and studies offer some promise but I try to see what's what.
 
Check here all the sides , is to much sides for such small gains ( the only gain i see from brasil people using is be all day without eating )

What are the possible side effects of Saxenda®?

Saxenda® may cause serious side effects, including:

inflammation of the pancreas (pancreatitis). Stop using Saxenda® and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your stomach area (abdomen) to your back.
gallbladder problems. Saxenda® may cause gallbladder problems, including gallstones. Some gallbladder problems need surgery. Call your health care provider if you have any of the following symptoms: pain in your upper stomach (abdomen), fever, yellowing of your skin or eyes (jaundice), or clay-colored stools.
increased risk of low blood sugar (hypoglycemia) in adults with type 2 diabetes who also take medicines to treat type 2 diabetes such as sulfonylureas or insulin.
risk of low blood sugar (hypoglycemia) in children who are 12 years of age and older without type 2 diabetes.
Signs and symptoms of low blood sugar may include: shakiness, sweating, headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, and feeling jittery. You should check your blood sugar before you start taking Saxenda® and while you take Saxenda®.
increased heart rate. Saxenda® can increase your heart rate while you are at rest. Your health care provider should check your heart rate while you take Saxenda®. Tell your health care professional if you feel your heart racing or pounding in your chest and it lasts for several minutes.
kidney problems (kidney failure). Saxenda® may cause nausea, vomiting, or diarrhea leading to loss of fluids (dehydration). Dehydration may cause kidney failure, which can lead to the need for dialysis. This can happen in people who have never had kidney problems before. Drinking plenty of fluids may reduce your chance of dehydration. Call your health care provider right away if you have nausea, vomiting, or diarrhea that does not go away, or if you cannot drink liquids by mouth.
serious allergic reactions. Stop using Saxenda® and get medical help right away if you have any symptoms of a serious allergic reaction including swelling of your face, lips, tongue, or throat, fainting or feeling dizzy, very rapid heartbeat, problems breathing or swallowing, or severe rash or itching.
depression or thoughts of suicide. You should pay attention to any mental changes, especially sudden changes, in your mood, behaviors, thoughts, or feelings. Call your health care provider right away if you have any mental changes that are new, worse, or worry you.

The most common side effects of Saxenda® in adults include nausea, diarrhea, constipation, vomiting, injection site reaction, low blood sugar (hypoglycemia), headache, tiredness (fatigue), dizziness, stomach pain, and change in enzyme (lipase) levels in your blood. Additional common side effects in children are fever and gastroenteritis.
 
Check here all the sides , is to much sides for such small gains ( the only gain i see from brasil people using is be all day without eating )

What are the possible side effects of Saxenda®?

Saxenda® may cause serious side effects, including:

inflammation of the pancreas (pancreatitis). Stop using Saxenda® and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your stomach area (abdomen) to your back.
gallbladder problems. Saxenda® may cause gallbladder problems, including gallstones. Some gallbladder problems need surgery. Call your health care provider if you have any of the following symptoms: pain in your upper stomach (abdomen), fever, yellowing of your skin or eyes (jaundice), or clay-colored stools.
increased risk of low blood sugar (hypoglycemia) in adults with type 2 diabetes who also take medicines to treat type 2 diabetes such as sulfonylureas or insulin.
risk of low blood sugar (hypoglycemia) in children who are 12 years of age and older without type 2 diabetes.
Signs and symptoms of low blood sugar may include: shakiness, sweating, headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, and feeling jittery. You should check your blood sugar before you start taking Saxenda® and while you take Saxenda®.
increased heart rate. Saxenda® can increase your heart rate while you are at rest. Your health care provider should check your heart rate while you take Saxenda®. Tell your health care professional if you feel your heart racing or pounding in your chest and it lasts for several minutes.
kidney problems (kidney failure). Saxenda® may cause nausea, vomiting, or diarrhea leading to loss of fluids (dehydration). Dehydration may cause kidney failure, which can lead to the need for dialysis. This can happen in people who have never had kidney problems before. Drinking plenty of fluids may reduce your chance of dehydration. Call your health care provider right away if you have nausea, vomiting, or diarrhea that does not go away, or if you cannot drink liquids by mouth.
serious allergic reactions. Stop using Saxenda® and get medical help right away if you have any symptoms of a serious allergic reaction including swelling of your face, lips, tongue, or throat, fainting or feeling dizzy, very rapid heartbeat, problems breathing or swallowing, or severe rash or itching.
depression or thoughts of suicide. You should pay attention to any mental changes, especially sudden changes, in your mood, behaviors, thoughts, or feelings. Call your health care provider right away if you have any mental changes that are new, worse, or worry you.

The most common side effects of Saxenda® in adults include nausea, diarrhea, constipation, vomiting, injection site reaction, low blood sugar (hypoglycemia), headache, tiredness (fatigue), dizziness, stomach pain, and change in enzyme (lipase) levels in your blood. Additional common side effects in children are fever and gastroenteritis.

These sides are very true many even on semaglutide liraglutide which are much less in dosage many feel sick no hunger I can’t imagine this as it’s 2.5mg twice the normal dose this would be not good for us as even the other ones at 1mg per week can have these side effects of sickness no hunger

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me as well !

So far I do not see what the studies show no extra muscle but I do not know how long you’d need to be on to see any gain as nobody has used to gain muscle on it yet and it’s not used in muscle waisting yet only obese for fat loss due to hunger loss

But from what we see in studies it’s promising but it also has the side effects you need to think about as it’s very serious the sickness hunger loss slowing of digestion you need low fat intake less then 30grams per day when I go higher in fat my hunger is gone I burp and do not digest food I can burp food from the previous day which is very bad
 
Conclusions: GLP-1R agonists ameliorate muscle wasting by suppressing MSTN and muscle atrophic factors and enhancing myogenic factors through GLP-1R-mediated signalling pathways. These novel findings suggest that activating GLP-1R signalling may be useful for the treatment of atrophy-related muscular diseases.

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Long acting GLP-1 analog liraglutide ameliorates skeletal muscle atrophy in rodents
Anagha Ashok Gurjar et al. Metabolism.

Background: Skeletal muscle atrophy is characterized by muscle wasting with partial or complete functional loss. Skeletal muscle atrophy severely affects the quality of life and currently, there is no available therapy except for spinal muscular atrophy.

Objective: Drug repositioning is a promising strategy that reduces cost and time due to prior availability of safety and toxicity details. Here we investigated myogenic and anti-atrophy effects of glucagon-like peptide-1 (GLP-1) analog liraglutide.

Methods: We used several in vitro atrophy models in C2C12 cells and in vivo models in Sprague Dawley rats to study Liraglutide's efficacy. Western blotting was used to assess cAMP-dependent signaling pathways specifically activated by liraglutide. Therapeutic efficacy of liraglutide was investigated by histological analysis of transverse muscle sections followed by morphometry. Myogenic capacity was investigated by immunoblotting for myogenic factors.

Results: Liraglutide induced myogenesis in C2C12 myoblasts through GLP-1 receptor via a cAMP-dependent complex network of signaling events involving protein kinase A, phosphoinositide 3-kinase/protein kinase B, p38 mitogen-activated protein kinase and extracellular signal-regulated kinase. Liraglutide imparted protection against freeze injury, denervation, and dexamethasone -induced skeletal muscle atrophy and improved muscular function in all these models. In a therapeutic model, liraglutide restored myofibrillar architecture in ovariectomy-induced atrophy. Anti-atrophy actions of liraglutide involved suppression of atrogene expression and enhancement in expression of myogenic factors.

Conclusion: Liraglutide imparted protection and restored myofibrillar architecture in diverse models of muscle atrophy. Given its potent anti-atrophy, and recently reported osteoanabolic effects, we propose liraglutide's clinical evaluation in skeletal muscle atrophy and musculoskeletal disorders associated with diverse pathologies.
 
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