0:00 Armando Hasirgun, Biology and Medicine videos, please make sure to subscribe, 0:05 join the forming 0:06 group for the latest videos, please visit Facebook, Armando Hasirgun, and here 0:10 you can 0:10 also like it, and please ask questions, answer questions, and post some 0:14 interesting things 0:15 such as artworks. 0:16 That would be greatly appreciated, and please change the quality settings to 0:20 the highest 0:21 one for better graphics of these videos. 0:23 In this video, we're going to talk about glucagon, a peptide hormone. 0:27 And its main role is in keeping the homostatic conditions on metabolism, and 0:32 its effects 0:33 are opposite to that of insulin. 0:35 Now within the pancreas we have these alpha cells, and as these alpha cells 0:38 which treat 0:38 glucagon, and as I mentioned, glucagon has opposite effects of insulin, where 0:42 insulin 0:43 wants to promote the storage of excess energy, glucagon wants to promote the 0:48 breakdown of 0:49 certain things in our body to provide energy for the body, so it essentially 0:53 signals the 0:54 fastened state, because for example, within the fastened state, you have low 0:58 blood glucose 0:59 level as in hypoglycemia, and then glucagon will be secreted, which will cause 1:05 the liver 1:06 to give glucose to the blood, to regulate the blood glucose levels. 1:12 And now I will show you the effects glucagon has on various organs within the 1:18 body when 1:19 we are in a fastened state. 1:21 So here we have the blood stream, and it has hypoglycemia, very low blood 1:27 glucose, and 1:28 here we have the liver, and adipose tissue, and also skeletal muscle. 1:32 Okay so we're in a fastened state with low blood glucose levels as in hypoglyce 1:37 mia. 1:38 This will cause the alpha cells to secrete glucagon. 1:41 What's important to know is that glucagon has no effect on skeletal muscle, 1:44 because 1:45 there are no glucagon receptors in skeletal muscle. 1:48 Glucagon does have an effect on adipose tissue though, and it stimulates the 1:52 breakdown or 1:52 degradation of tricer glycerols into glycerol and fatty acids. 1:56 These fatty acids and glycerol will then travel to the liver. 2:00 Glucagon will promote the conversion of fatty acids to ketone bodies, so that 2:04 ketone bodies 2:04 can be used as a source of fuel during the fastened state, for the brain and 2:09 skeletal 2:09 muscle for example. 2:12 Glucagon will also promote gluconeogenesis to make more glucose, because now 2:15 the liver 2:16 has glycerol, glycerol can go through gluconeogenesis to be converted to 2:21 glucose 6-phosphate. 2:23 Glucagon, sorry, also promotes the breakdown of glycogen via gluconeogenesis as 2:29 well to 2:30 make glucose 6-phosphate, and glucose 6-phosphate can then be converted to 2:34 glucose. 2:34 And then this is when the liver secrets glucose in the bloodstream to regulate 2:39 the blood glucose 2:40 levels, to increase glucose blood glucose levels. 2:44 The proteins in the liver can go via proteolysis to make amino acids, and these 2:50 amino acids 2:51 can then be fed into gluconeogenesis to make glucose 6-phosphate and then 2:56 glucose. 2:57 And this is also promoted by glucagon, and it's important to note that the 3:02 muscles can 3:03 also provide amino acids into the liver during a fastened state, but this is 3:08 not caused by 3:09 the effects of glucagon, because remember glucagon has no effect on skeletal 3:14 muscle. 3:15 And so that was an overview of the effects glucagon has on various origins, and 3:20 how it 3:20 causes it to degradate many things to provide energy to the blood as in glucose 3:28 . 3:28 Now let's look at how glucagon is synthesized. 3:33 Now glucagon synthesis is very similar to the insulin, because they're both 3:38 peptide hormones. 3:39 So here we have the pancreas, and glucagon synthesis occurs in the alpha cells 3:44 of the 3:45 pancreas, because it's these alpha cells which essentially secrets glucagon. 3:50 And within these alpha cells we have this ribosome, which is translating an MR 3:54 NA, MRRNA 3:55 for glucagon. 3:57 Okay, and so this protein, polypeptide, is pre-pro-glucagon. 4:03 Pre-pro-glucagon, which has just been translated, will then travel to the end 4:06 oplasmic reticulum 4:07 to get cleaved up and sorted out to make pro-glucagon. 4:11 The pro-glucagon is then cleaved up into three different peptides by a 4:17 particular enzyme. 4:19 And now the three peptides form, polypeptides form, is a 29 amino acid glucagon 4:24 , the actual 4:25 hormone we're looking at. 4:26 It also creates a small polypeptide, known as GRPP, glycentin-related pancreat 4:31 ic peptide, 4:32 and also another long one, called the major pro-glucagon fragment. 4:36 But we're not looking at these other ones, we're concentrating on the 29 amino 4:39 acid glucagon. 4:40 Anyways, once glucagon is formed, glucagon can then be secreted by the alpha 4:45 cells and 4:45 by the pancreas essentially into the bloodstream. 4:48 Glucagon will then travel through the bloodstream to its target tissue. 4:51 It can be adipose tissue, or it can be even the liver. 4:55 Let's trail off there for a bit and look at the intestines. 4:58 So remember the pancreas has a pancreat duct, where it can secrete its 5:03 digestive enzymes 5:04 into the intestines, into the duodenum, to help in the digestive process after 5:09 we eat. 5:10 Well, anyway, in the duodenum we have the intestinal cells. 5:15 And what's very interesting is that the intestinal cells also has a gene that 5:21 transcribes for 5:22 glucagon, very similar genes to the one found in the alpha cells. 5:27 So essentially, if we follow this route, we can say that this gene will make an 5:34 mRNA, 5:35 which is for glucagon, very exactly the same, and then the ribosome will 5:40 translate it to 5:41 a pre-pro-glucagon. 5:43 The pre-pro-glucagon will then travel to the endoplasmic reticulum to form pro- 5:47 glucagon, 5:48 also the same as the alpha cells, except now the pro-glucagon is cleaved up by 5:52 a different 5:53 mechanism and by different things to form three different polypeptides. 5:59 And these polypeptides is the 2069 amino acid glycentin, and then we have the 6:04 glucone-like 6:04 peptide one and glucone-like peptide two. 6:07 Now, glycentin can then be also cleaved up into two other peptides. 6:12 The GRPP, glycentin-related pancreatic peptide, exactly the same as the one 6:18 from the alpha 6:19 cells, and also another one called oxolotoneomodulin, hope I pronounced that 6:25 right. 6:26 And anyway, this oxolotoneomodulin, interestingly enough, has a role, potential 6:31 role in suppressing 6:32 appetite, something interesting to note. 6:35 Anyway, now that we know how glucone is synthesized from the alpha cells, we 6:39 can see how it affects 6:41 the target tissue, such as the liver here. 6:43 So the liver has a receptor which glucone can bind to and initiates its effects 6:47 in degradation 6:48 of stuff to be released into the bloodstream, for example. 6:53 So what receptor does glucone actually bind to to initiate its intracellular 6:57 effects? 6:58 Well, if we zoom into the liver here, we can see the liver has a membrane and 7:02 it has a 7:03 special receptor known as a G protein-coupled receptor with a G protein in the 7:07 intracellular 7:08 fluid. 7:09 And then we have the effect of protein adenylate cyclase over here, which is an 7:14 enzyme. 7:14 And here's the outside of the cell and here's the inside of the cell. 7:18 And now, if you don't know what a G protein-coupled receptor is, you can watch 7:22 a video 7:22 on my video on the G protein-coupled receptor, which is in the pharmacology 7:26 playlist, I'm 7:27 pretty sure. 7:30 Now within the cell, we also have a special enzyme known as protein kinase A, P 7:35 KA. 7:36 But protein kinase A is inactive because it's bound and anchored by a protein 7:41 known as the 7:42 A kinase anchoring protein. 7:45 And so this PKA, two PKAs are bound to the regulatory subunits of this AKAP, 7:52 and which 7:53 makes it inactive, you can say. 7:57 So how do we activate this protein kinase A? 8:01 Well, glucone can bind onto the G protein-coupled receptor, which will create a 8:05 conformational 8:06 change, which will cause the intracellular G protein to move and activate the 8:10 adenylate 8:11 cyclase. 8:12 The activated adenylate cyclase can then convert ATP to cyclic AMP. 8:17 And per glucone stimulation, cyclic adenylate cyclase can make about times 20 8:23 cyclic AMPs. 8:24 Let's just say, and interestingly enough, cyclic AMP can activate protein kin 8:30 ase A. 8:31 How does it do this? 8:32 Well, two cyclic AMPs combine onto the regulatory subunit of AKAP, the A kinase 8:39 anchoring protein, 8:41 which will then cause the protein kinase A to disassociate and become activated 8:46 . 8:46 And as you can see with this diagram, there is four cyclic AMPs, which binds to 8:51 two regulatory 8:52 subunits, which activates two protein kinase A. 8:55 Therefore, if we have 20 cyclic AMPs, this would mean that it will activate 10 9:03 pKa's. 9:03 So 10 protein kinase A's are now activated. 9:07 And protein kinase A, when it becomes activated, can then cause the intrace 9:12 llular effects of 9:13 glucone. 9:14 Because this is the liver, pKa will cause an increase in glycogen degradation. 9:21 It will cause a decrease in glycogen synthesis. 9:24 It will cause a decrease in glycolysis. 9:27 And it will cause an increase in gluconeogenesis, because we want more glucose 9:32 to remember. 9:33 Of course, glucone has many other effects on different types of organs, such as 9:38 adipose 9:38 tissue, and it promotes lipolysis, for example. 9:41 So now let's look at a more deeper into the effects glucone has on various 9:47 processes in 9:48 promoting the breakdown of macromolecules. 9:50 And sorry for the incorrect spelling, it's meant to be a glucagon on glycogen. 9:55 So glucone promotes the degradation of glycogen into glucose by stimulating the 10:01 enzyme glycogen 10:02 phosphorylase. 10:04 Glucagon does inhibits the synthesis of glycogen from glucose, and so it 10:09 inhibits the enzyme 10:11 glycogen synthase. 10:13 Glucagon also inhibits glycolysis, the conversion of glucose to pyroben, and so 10:18 inhibits the 10:19 enzyme protein phosphofructoplanes 1, one of the many proteins associated with 10:23 this process. 10:26 Glucagon also stimulates gluconeogenesis by stimulating the conversion of acyl 10:31 coA, pyruvate, 10:33 and even oxaloacetate into glucose. 10:36 And this is through the enzyme, particularly glucose-6 phosphatase. 10:42 Glucagon also stimulates the degradation of triacylglycerols to glycerol and 10:47 fatty acid, 10:48 and so stimulates the enzyme hormone-sensitive lipase. 10:53 Glucone stimulates the conversion of fatty acids to acylcoA. 10:57 And then glucone, as I mentioned, stimulates gluconeogenesis, which stimulates 11:01 the conversion 11:02 of glycerol and acylcoA to glucose. 11:08 And importantly, actually, glucone also stimulates the synthesis of ketone 11:12 bodies to provide energy 11:14 to different organs during the fasted state. 11:18 And that concludes the video on glucone. 11:19 I hope you enjoy it. 11:20 Please like, comment, and share. 11:21 Thank you.
