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Glp-1
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Glp-1 - 10-11-2011, 08:34 PM

Glucagon-like peptide-1 (GLP-1) is derived from the transcription product of the proglucagon gene. The major source of GLP-1 in the body is the intestinal L cell that secretes GLP-1 as a gut hormone. The biologically active forms of GLP-1 are: GLP-1-(7-37) and GLP-1-(7-36)NH2. Those peptides result from selective cleavage of the proglucagon molecule.

GLP-1 secretion by ileal L cells is dependent on the presence of nutrients in the lumen of the small intestine. The secretagogues (agents that cause or stimulate secretion) of this hormone include major nutrients like carbohydrate, protein and lipid. Once in the circulation, GLP-1 has a half-life of less than 2 minutes, due to rapid degradation by the enzyme dipeptidyl peptidase-4. It is a potent antihyperglycemic hormone, inducing glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion. Such glucose-dependent action is particularly attractive because, when the plasma glucose concentration is in the normal fasting range, GLP-1 no longer stimulates insulin to cause hypoglycemia. GLP-1 appears to restore the glucose sensitivity of pancreatic β-cells, with the mechanism possibly involving the increased expression of GLUT2 and glucokinase. GLP-1 is also known to inhibit pancreatic β-cell apoptosis and stimulate the proliferation and differentiation of insulin-secreting β-cells. In addition, GLP-1 inhibits gastric secretion and motility. This delays and protracts carbohydrate absorption and contributes to a satiating effect.
   
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GLP-1 Agonists/Effects
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GLP-1 Agonists/Effects - 10-11-2011, 08:34 PM

By: chemicalwarrior


(Warning, this is unedited and kind of stream-of-consciousness thoughts on the subject written at 1:30 am...)

GLP-1 Agonists and why we Gym Rats Might be Interested

GLP-1 (Glucagon-like peptide) is a strange bird. It has a very short half-life of 2 minutes in the body and while it increases insulin secretion it also slows gastric emptying. Someone asked me recently if it would make a good replacement for insulin as used by bodybuilders. And, the short answer to that is no. Since it slows gastric emptying there'd be no call for using it as you would humalog or humalin-r pre or post workout. The carbs, aminos, creatine etc. just wouldn't get into the system fast enough to work their magic as they do with regular insulin. But, a better explanation is that it would be to insulin as a good PCT is to a heavy steroid cycle. I'll get into that in a minute. Plus, because of its short half-life it is basically useless in and of itself. What we want is a good GLP-1 "agonist" and that's where exenatide comes in.

Exenatide (trade name Byetta) was discovered in the saliva of gila monsters and is actually found concentrated in the tails. Hence the slang term for it "lizard spit!" lol. It only shares a 50% identical amino acid sequence to GLP-1 thus making it an "agonist" or promoter of GLP-1 vs actually being a copy or analogue. The benefit to all this is that because of its structure it produces many of the same positive effects but is prevented by being broken down by GPP-4, the protein that is present throughout the body that destroys GLP-1, so quickly. Thus exenatide has a much longer half life and is injected only twice per day in a similar way that we use our GH secretogues: subcuteneous injections, 1 hr before a meal on an empty stomach.

Now, for a bodybuilder, what are the benefits of exenatide?

1) Induces Insulin secretion/Increases insulin sensitivity- This is important after a period of use of GH, insulin, IGF-1, steroids etc. All which tend to decrease insulin sensitivity over time. Think about it: When we come off a long steroid cycle we use something to get the "boys" working again and the testosterone flowing. With insulin being the most anabolic of all hormones shouldn't we also seek to maximize our own natural production and sensitivity?

2) Slows gastric emptying- This happens because of exenatide's ability to block glucagon release. Hence, we get a sense of being fuller, longer. And, essentially we are. This is the value we derive from eating whole wheat products vs high glycemic white bread. With a slower release of nutrients into the system we get a less "jagged" insulin spike = less carbs stored as fat! But, with the effect of increased insulin sensitivity, our bodies make better use of what glucose is in the system, i.e. makes us more "efficient" at using what we eat! A word of caution here. Since exenatide slows gastric emptying, it should never, ever be used in direct conjunction (at the same time) with insulin. While you are trying to get those carbs into your system to prevent a blood glucose crash, exenetide will be slowing down the release of those nutrients in your gut! Big trouble potential!!

With these two properties, exenatide appears to be a great product for use during a pre-contest diet that includes, and especially one that cycles, carbs. Since its effects are glucose dependent (i.e. the more carbs you eat, the more insulin is released) you will likely be able to tolerate more carbs while dieting than before while yet remaining insulin sensitive and putting them to use- though I, obviously, wouldn't try to eat more carbs than you need in this situation. In various trials people lost an average of 7 lbs over the course of some 26 weeks. But, these were average schlubs, not bodybuilders actually trying to burn fat and using other supplements along the way. Combining exenatide with a little bit of t-3 and a healthy dose of test might be a great combo while tackling a tough contest diet. Just a thought.

So, if you want to maximize insulin sensitivity and carb utilization, exenatide may be an interesting option at some point. Though it wouldn't be an ideal candidate for bulking/gaining cycles (the slow gastric emptying will make you actually want to eat less), it may be just what the doctor ordered while trimming off excess fat after a bulk cycle. The usual peptide side-effect of occasional nausea was reported (though I'm used to that with mt2 and other peps). But, for the most part it has been well tolerated and would seem to be, overall, a "healthy" drug as it evens out blood glucose spikes and tends to help trim the waistline.

I haven't tried it yet. But, when I get the chance I'm gonna give it a go just based on the little bit of research I've done. Go out and google it. Read about other options for these benefits and I'll think you'll see why I'm talking about this drug. It's a kind of "middle of the road" thing: it's more powerful/effective than metformin but with much, much less risk of going hypoglycemic as you might with actual insulin. The half-life is much longer than GLP-1 but shorter than a couple other GLP-1 analogues that are in the works. These analogues often last for a day and some for up to ten days! No thanks, I'd like to have a bit more control over what my system is doing. i.e. if I wanted to have some insulin pre-workout, I still could with exenatide. I'd just schedule doses far enough away that they didn't overlap in any way- exenatide 7 am, humalog 4 pm pre workout, exenatide 8:30 pm... or something like that.. Not recomending that, but I'd just rather have some control and know it'd be out of my system in a matter of hours vs. days.

Ok, I'm rambling now. These are just some thoughts. Like I say, check it out for yourself, lots of info out there on this and other interesting peptides of this sort.
   
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More - 10-11-2011, 08:36 PM

By: alan1973


we have to make sure we are careful with our souces....this is produced in E-Coli!!!
I have info on this from another site that I am gonna paste here..but I will not cite the source for fear of getting banned for posting sources that are not sponsors.


Glucagon-Like Peptide (GLP)-1, human produced in E. coli is a single, non-glycosylated, polypeptide chain containing 30 amino acids and having a molecular mass of 3,298.7 Da. GLP-1 is a incretion hormone, which has been shown to stimulate secretion of insulin in the presence of elevated blood glucose concentrations, but not during periods of low blood glucose concentrations (hypoglycemia). GLP-1 is an insulinotropic hormone that has the ability to render pancreatic beta cells glucose-competent. It has been used in the therapy of type-2 diabetes. GLP-1 has activities of cyokines, although it is not classified as such due its small size GLP-1 enhances cell differentiation, plays a role in tissue regeneration, and mediates cytoprotection. rHuGLP-1 is purified by proprietary chromatographic techniques.
Source E. coli
M.W. 3,298.7 Da
Purity Greater than 95.0% as determined by the following methods:
(a) Analysis by RP-HPLC
(b) Analysis by SDS-PAGE
Endotoxin Level Less than 0.1 ng/g (IEU/g) of rHuGLP-1
Specific Activity 1. Regulates glucose levels rapidly
2. Reduces insulin resistance
3. Reduces glucagon
4. Reduces HbA1c
5. Stimulates beta cell growth, which in turn stimulates insulin production
Storage Although lyophilized rHuGLP-1 can remain stable at room temperature for three weeks, it is best stored desiccated below -18C. Upon reconstitution, rHuGLP-1 may be stored at 4C for up to one week and below -18C for longer periods.
For long-term storage it is recommended that a carrier protein (0.1% HSA or BSA) be added. Avoid freeze-thaw cycles.
Formulation The protein (1 mg/ml) is lyophilized after extensive dialyses against 0.1 mg sodium phosphate monobasic and 1.6 mg sodium phosphate dibasic.
Reconstitution It is recommended that the lyophilized rHuGLP-1 be reconstituted in sterile 18 MΩ-cm H2O of not less than 100 g/ml, which can then be further diluted to other aqueous solutions.
Quantitation protein quantitation is carried out by two independent methods:
1. UV spectroscopy at 280 nm
2. RP-HPLC analysis, using a calibrated solution of GLP-1 as a reference standard
Stability Lyophilized Glucagon Like Peptide-1 although stable at room temperature for 3 weeks, should be stored desiccated below -18C. Upon reconstitution GLP-1 should be stored at 4C between 2-7 days and for future use below -18C. For long term storage it is recommended to add a carrier protein (0.1% HSA or BSA). Please prevent freeze-thaw cycles.
Sequence analysis The sequence of the first five N-terminal amino acids has been found to be His-Ala-Glu-Gly-Thr.
   
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07-01-2012, 03:02 PM

Quote:
Originally Posted by PRIDE. View Post
GLP-1 (Glucagon-like peptide) is a strange bird.. But, a better explanation is that it would be to insulin as a good PCT is to a heavy steroid cycle.
what stuff would be the best one to use in order to enhance and recover/(resrore) the right own natural insulin production at pancreas if any BB would damage getting a decreasement a at its own insulin production by too much exogenous insulin administration over the years? would peptides as GLP-1 and Exenatide be the best and the world's most powerful insulin releasers to use or would other peptides/stuff be?
Is GLP-1 more or less powerful than sulphanylureas to stimulate own insulin production?

Quote:
Originally Posted by PRIDE. View Post
Thus exenatide has a much longer half life and is injected only twice per day in a similar way that we use our GH secretogues
How many iu insulin is an exenatide cycle supposed to equate to?



Quote:
Originally Posted by PRIDE. View Post
Since exenatide slows gastric emptying, it should never, ever be used in direct conjunction (at the same time) with insulin. While you are trying to get those carbs into your system to prevent a blood glucose crash, exenetide will be slowing down the release of those nutrients in your gut! Big trouble potential!!
Let's suppose exenate gets someone on hypo ,so i start to eat carbs. Then let's suppose he practice a Glucagon shot too in order to raise sugar in blood (and so insulin production too). What will it happen at his own insulin production? will he get a huge hypoglicemic shock?


Quote:
Originally Posted by PRIDE. View Post
The half-life is much longer than GLP-1 but shorter than a couple other GLP-1 analogues that are in the works. These analogues often last for a day and some for up to ten days!
what should anyone do to make sure his GLP-1 bought be a short-action and not a long-action one? what does he do to recognize a real rh-GLP-1 short-action than a long-action GLP-1 analogue? Have they different names?

thanxs a bunch
   
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Lightbulb 07-01-2012, 11:35 PM

Quote:
Originally Posted by PRIDE. View Post
By: alan1973


we have to make sure we are careful with our souces....this is produced in E-Coli!!!
I have info on this from another site that I am gonna paste here..but I will not cite the source for fear of getting banned for posting sources that are not sponsors.


Glucagon-Like Peptide (GLP)-1, human produced in E. coli is a single, non-glycosylated, polypeptide chain containing 30 amino acids and having a molecular mass of 3,298.7 Da. GLP-1 is a incretion hormone, which has been shown to stimulate secretion of insulin in the presence of elevated blood glucose concentrations, but not during periods of low blood glucose concentrations (hypoglycemia). GLP-1 is an insulinotropic hormone that has the ability to render pancreatic beta cells glucose-competent. It has been used in the therapy of type-2 diabetes. GLP-1 has activities of cyokines, although it is not classified as such due its small size GLP-1 enhances cell differentiation, plays a role in tissue regeneration, and mediates cytoprotection. rHuGLP-1 is purified by proprietary chromatographic techniques.
Source E. coli
M.W. 3,298.7 Da
Purity Greater than 95.0% as determined by the following methods:
(a) Analysis by RP-HPLC
(b) Analysis by SDS-PAGE
Endotoxin Level Less than 0.1 ng/g (IEU/g) of rHuGLP-1
Specific Activity 1. Regulates glucose levels rapidly
2. Reduces insulin resistance
3. Reduces glucagon
4. Reduces HbA1c
5. Stimulates beta cell growth, which in turn stimulates insulin production
Storage Although lyophilized rHuGLP-1 can remain stable at room temperature for three weeks, it is best stored desiccated below -18C. Upon reconstitution, rHuGLP-1 may be stored at 4C for up to one week and below -18C for longer periods.
For long-term storage it is recommended that a carrier protein (0.1% HSA or BSA) be added. Avoid freeze-thaw cycles.
Formulation The protein (1 mg/ml) is lyophilized after extensive dialyses against 0.1 mg sodium phosphate monobasic and 1.6 mg sodium phosphate dibasic.
Reconstitution It is recommended that the lyophilized rHuGLP-1 be reconstituted in sterile 18 MΩ-cm H2O of not less than 100 g/ml, which can then be further diluted to other aqueous solutions.
Quantitation protein quantitation is carried out by two independent methods:
1. UV spectroscopy at 280 nm
2. RP-HPLC analysis, using a calibrated solution of GLP-1 as a reference standard
Stability Lyophilized Glucagon Like Peptide-1 although stable at room temperature for 3 weeks, should be stored desiccated below -18C. Upon reconstitution GLP-1 should be stored at 4C between 2-7 days and for future use below -18C. For long term storage it is recommended to add a carrier protein (0.1% HSA or BSA). Please prevent freeze-thaw cycles.
Sequence analysis The sequence of the first five N-terminal amino acids has been found to be His-Ala-Glu-Gly-Thr.
Being produced from ecoli is a concern to me.
   
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