Latest / The Peptide Research Podcast / Episode 89: What is Glucagon and what does it have to do with Retatrutide

Transcript

Episode 89: What is Glucagon and what does it have to do with Retatrutide · The Peptide Research Podcast

• 0:45
  SPEAKER_02: Here's something that sounds like a mistake.
• 0:47
  SPEAKER_02: Researchers are studying a new compound.
• 0:49
  SPEAKER_02: It switches on three different signals in the body, and one of those three is the signal that raises your blood sugar.
• 0:57
  SPEAKER_00: It does sound like a mistake.
• 0:59
  SPEAKER_02: Somebody put that in there on purpose.
• 1:02
  SPEAKER_02: Today is the whole show on why.
• 1:04
  SPEAKER_00: This is part of our ongoing series on the GLP compounds.
• 1:08
  SPEAKER_00: Hit follow so the next one lands in your feed automatically.
• 1:11
  SPEAKER_02: I'm Amy Andrews, and this is the PeptideResearch.us podcast.
• 1:16
  SPEAKER_02: Todd Collins is with me.
• 1:17
  SPEAKER_02: Today we're looking at one piece of a compound called retitrutide, the blood sugar piece.
• 1:23
  SPEAKER_02: Todd, what does somebody walk away knowing?
• 1:26
  SPEAKER_00: What that signal actually does, why researchers wanted it in the mix instead of out of it, and why it only makes sense when it's paired with something else.
• 1:35
  SPEAKER_00: One note before we start.
• 1:37
  SPEAKER_00: All peptides discussed in this podcast relate to research use only.
• 1:41
  SPEAKER_00: Any references to data from animals, cells, or human studies relate exclusively to scientific literature and not to products from NRG biolabs.
• 1:51
  SPEAKER_00: These compounds are not approved drugs or dietary supplements and are not for human consumption.
• 1:56
  SPEAKER_00: Nothing in this podcast is medical advice.
• 1:59
  SPEAKER_01: Okay.
• 2:00
  SPEAKER_01: Start me at zero.
• 2:01
  SPEAKER_00: Here's the simple version.
• 2:03
  SPEAKER_00: Your body keeps fuel in storage.
• 2:05
  SPEAKER_00: Something has to tell it when to open the storage up.
• 2:08
  SPEAKER_00: That's one signal's entire job.
• 2:11
  SPEAKER_00: It goes out when fuel in your blood is running low.
• 2:14
  SPEAKER_01: Oh, so it's a withdrawal slip.
• 2:16
  SPEAKER_01: Insulin is the deposit slip, that's the one everybody knows.
• 2:20
  SPEAKER_01: This is the other half.
• 2:21
  SPEAKER_01: Money in, money out.
• 2:23
  SPEAKER_00: That's exactly it.
• 2:24
  SPEAKER_00: And that withdrawal signal has a name.
• 2:27
  SPEAKER_00: Researchers call it glucagon.
• 2:29
  SPEAKER_01: Glucagon.
• 2:30
  SPEAKER_01: Okay, where does it go?
• 2:32
  SPEAKER_00: Almost every cell can hear it, but only some cells have the lock it fits.
• 2:37
  SPEAKER_00: And the liver has far more of those locks than anywhere else.
• 2:40
  SPEAKER_00: So when glucagon goes out, it's really one organ being spoken to by name.
• 2:45
  SPEAKER_02: So the liver is the branch where my account actually lives.
• 2:50
  SPEAKER_00: I'm stealing that.
• 2:51
  SPEAKER_02: Here's my follow-up though.
• 2:53
  SPEAKER_02: Does the liver only hand back sugar?
• 2:56
  SPEAKER_00: No, and this is the part people miss.
• 2:59
  SPEAKER_00: The liver holds two kinds of reserve.
• 3:01
  SPEAKER_00: There's sugar, it keeps on hand, and there's fat.
• 3:05
  SPEAKER_00: Glucagon tells it to spend both.
• 3:07
  SPEAKER_00: Same instruction, two different shelves.
• 3:10
  SPEAKER_00: Lab insight.
• 3:11
  SPEAKER_00: Here's what that looks like on a bench.
• 3:13
  SPEAKER_00: Put two compounds side by side.
• 3:16
  SPEAKER_00: One carries the glucagon signal, one doesn't.
• 3:19
  SPEAKER_00: Then look at the liver itself.
• 3:21
  SPEAKER_00: In animal studies, the one carrying glucagon leaves less fat sitting inside the liver.
• 3:27
  SPEAKER_00: Take that signal out, and most of the difference goes with it.
• 3:30
  SPEAKER_02: Wait, so it isn't really a sugar hormone at all?
• 3:34
  SPEAKER_00: It's a spending hormone.
• 3:36
  SPEAKER_00: Sugar is just what it spends first.
• 3:39
  SPEAKER_02: Then why isn't it obvious?
• 3:41
  SPEAKER_02: Why not study glucagon on its own?
• 3:44
  SPEAKER_00: Because of the thing you flagged at the top.
• 3:46
  SPEAKER_00: Push it by itself, and yes, the body opens the reserves and burns more fat for fuel.
• 3:51
  SPEAKER_00: It also pushes blood sugar up, and that's the one direction this whole field has spent 30 years trying to move away from.
• 3:59
  SPEAKER_00: On its own, it's a bad trade.
• 4:01
  SPEAKER_02: So what makes it a good idea with company?
• 4:05
  SPEAKER_00: A second signal.
• 4:06
  SPEAKER_00: Your gut sends this one out when you eat.
• 4:09
  SPEAKER_00: It nudges blood sugar the other way, down.
• 4:11
  SPEAKER_00: Researchers call it GLP1.
• 4:14
  SPEAKER_02: So one pushes sugar up, one pulls it down.
• 4:18
  SPEAKER_00: Right.
• 4:19
  SPEAKER_00: The bet is that those two mostly cancel, and when they do, the fuel spending part of glucagon is still there.
• 4:26
  SPEAKER_02: Oh, that's a hot air balloon.
• 4:28
  SPEAKER_02: The burner pushes you up, the vent lets you back down.
• 4:32
  SPEAKER_02: You're not trying to win with either one.
• 4:34
  SPEAKER_02: You run both so you can hold steady and actually go somewhere.
• 4:39
  SPEAKER_02: Level two question.
• 4:40
  SPEAKER_02: Does canceling out just leave you with nothing?
• 4:44
  SPEAKER_00: That's exactly the right worry.
• 4:46
  SPEAKER_00: It comes down to how hard each signal gets pushed.
• 4:49
  SPEAKER_00: Lean too far one way and the blood sugar problem wins.
• 4:52
  SPEAKER_00: Lean too far the other way, and you've built something that only does what GLP1 already did.
• 4:58
  SPEAKER_00: Getting that balance right is the whole job.
• 5:01
  SPEAKER_00: Lab Insight.
• 5:02
  SPEAKER_00: In animal studies, you can watch it happen.
• 5:05
  SPEAKER_00: Run glucagon on its own, and blood sugar drifts up while the animal burns more energy sitting still.
• 5:11
  SPEAKER_00: Add the GLP1 signal, and that drift flattens out.
• 5:15
  SPEAKER_00: The energy part stays.
• 5:16
  SPEAKER_00: Neither signal is doing anything new, they're editing each other.
• 5:20
  SPEAKER_02: Okay, who thought of pairing them?
• 5:22
  SPEAKER_02: Because that sounds very modern.
• 5:25
  SPEAKER_00: This is my favorite part.
• 5:27
  SPEAKER_00: The body did, a long time before we did.
• 5:30
  SPEAKER_00: There's a hormone your gut already makes that doesn't do one job.
• 5:34
  SPEAKER_00: It switches on the GLP1 signal and the glucagon signal, both, at the same time.
• 5:40
  SPEAKER_02: Wait, what?
• 5:42
  SPEAKER_02: The combination already existed?
• 5:45
  SPEAKER_00: It already existed.
• 5:46
  SPEAKER_00: Nobody designed it.
• 5:48
  SPEAKER_00: It's called oxyantomulin, and that's the hardest word in today's episode.
• 5:52
  SPEAKER_00: I promise it's the last one.
• 5:55
  SPEAKER_02: Oh, I love that.
• 5:56
  SPEAKER_02: That's inventing a tool, being extremely proud of yourself, and then finding the exact same tool in your grandfather's toolbox with the handle already worn smooth.
• 6:06
  SPEAKER_02: Level two.
• 6:07
  SPEAKER_02: If the body makes one, why build one?
• 6:10
  SPEAKER_00: Two reasons.
• 6:11
  SPEAKER_00: The natural one doesn't stick around.
• 6:13
  SPEAKER_00: Your body takes it apart in minutes.
• 6:16
  SPEAKER_00: And the balance between its two jobs is whatever biology happened to land on, not what a researcher wants to test.
• 6:23
  SPEAKER_00: A built molecule lets you hold it steady and turn each part up or down on purpose.
• 6:28
  SPEAKER_00: That's the difference between watching something and actually studying it.
• 6:32
  SPEAKER_01: Did you see that shift happen?
• 6:34
  SPEAKER_00: I saw it and I got it wrong.
• 6:36
  SPEAKER_00: Early on, I sat through a poster on oxyantomulin, and I filed the whole thing under odd, a hormone that couldn't decide what it was.
• 6:45
  SPEAKER_00: I thought it was messy.
• 6:46
  SPEAKER_00: The messiness was the blueprint.
• 6:48
  SPEAKER_00: Ten years on, the field builds molecules to be messy on purpose.
• 6:53
  SPEAKER_02: I'll give you the listener version of that.
• 6:55
  SPEAKER_02: I learned hormones as a cast list.
• 6:58
  SPEAKER_02: Insulin good, glucagon bad, cortisol, villain.
• 7:02
  SPEAKER_02: I carried that around for years and never once questioned it.
• 7:06
  SPEAKER_02: What finally broke it was realizing the body doesn't have villains.
• 7:10
  SPEAKER_02: It has signals that are right at some moments and wrong at others.
• 7:15
  SPEAKER_02: And the one I'd written off as the bad guy is sitting in the middle of the most interesting work in the field.
• 7:21
  SPEAKER_00: Direction and timing.
• 7:23
  SPEAKER_00: Nothing in there is good or bad.
• 7:25
  SPEAKER_00: It's either aimed well or it isn't.
• 7:28
  SPEAKER_02: And everything we've described today is a balance, which is exactly why it matters where a compound comes from.
• 7:34
  SPEAKER_00: Right.
• 7:35
  SPEAKER_00: If what you're studying is a balance between three signals, then the one thing you can't afford is doubt about what's in the vial.
• 7:42
  SPEAKER_00: That's why NRG Biolabs is the foundational partner behind this show.
• 7:46
  SPEAKER_00: Third-party testing, batch-by-batch paperwork, certificates of analysis, the documents that say what's actually in there.
• 7:54
  SPEAKER_00: You can see the COAs and view the lab standards at peptidesearch.us.
• 7:59
  SPEAKER_02: You can't study a balance you don't trust.
• 8:03
  SPEAKER_00: Not honestly.
• 8:04
  SPEAKER_02: Let me pull it together.
• 8:05
  SPEAKER_02: Glucagon is the body's withdrawal slip.
• 8:08
  SPEAKER_02: It talks mostly to the liver and it tells the liver to spend both shelves, sugar and fat.
• 8:15
  SPEAKER_00: Right.
• 8:15
  SPEAKER_02: On its own, it drags blood sugar the wrong way so it doesn't get studied alone.
• 8:21
  SPEAKER_02: Pair it with GLP1 and the sugar effects push against each other while the spending part stays.
• 8:28
  SPEAKER_00: That's the bet.
• 8:29
  SPEAKER_02: And the body already made a two-job version called oxyentomulin long before anybody thought to build one.
• 8:37
  SPEAKER_00: That's a fair summary.
• 8:39
  SPEAKER_00: Oh, and one last thing that's easy to overlook.
• 8:42
  SPEAKER_00: We talk about this compound reaching three signals, like the number is the achievement.
• 8:47
  SPEAKER_00: It isn't.
• 8:48
  SPEAKER_00: Two of the three were already being reached by things we had.
• 8:51
  SPEAKER_00: The real departure is that somebody was willing to include a signal the whole field had spent a generation trying to shut down.
• 8:58
  SPEAKER_02: Oh, I see.
• 9:00
  SPEAKER_02: The new part wasn't the molecule, it was permission.
• 9:03
  SPEAKER_02: If you want to sit with this one slowly, there's a plain English write-up on glucagon and this compound at peptidesearch.us.
• 9:11
  SPEAKER_02: The peptide research section is where I'd start.
• 9:14
  SPEAKER_02: And if today's breakdown was useful, follow the show.
• 9:17
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• 9:24
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• 9:35
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• 9:40
  SPEAKER_02: That's our show.
• 9:41
  SPEAKER_02: Thanks for thinking out loud with us.