Talk:Glucagon-like peptide-1

Redirect
Can someone please make the acronym "Glp1" redirect to this article rather than to the article on "Glucagon". —Preceding unsigned comment added by 59.101.48.57 (talk) 10:50, 16 June 2008
 * I am no biologist, and Wikipedia's article at Glucagon is confusing in this regard. However, your proposal makes sense at face value.  So, I changed the redirect: please click on GLP1 now.  --Hroðulf (or Hrothulf) (Talk) 13:28, 16 June 2008 (UTC)

Can we please get some kind of listing of the mechanism of action in this article? What kind of protein systems does this interact with? What kind of receptor does it interact with? --Bobsagat 22:49 CST, Feb. 8th 2009 —Preceding unsigned comment added by Bobsagat (talk • contribs) 04:50, 9 February 2009 (UTC)

Sucralose
The discussion on what stimulates GLP-1 release should add that sucralose does. E.g., Margolskee, R.F. 2006. Molecular biology of taste perception. Diabetes. 55(Suppl. 1):35, or Cummings and Overduin, J. Clin. Invest. 117(1): 13-23 (2007), who reference the former, as well as others. I am no biologist, however. peter (talk) 23:15, 15 April 2009 (UTC)

add table
It would be nice to see the generic table on the right side of the article showing accession numbers, etc. I propose following for human (resides in the glucagon sequence):

UniProt: P01275 Seq: HDEFERHAEG TFTSDVSSYL EGQAAKEFIA WLVKGRG pI: 5.05 MW: 4169.54

I work with GLP-1 and believe this to be correct. Hope this helps!

Dee — Preceding unsigned comment added by Deewells (talk • contribs) 15:19, 5 October 2011 (UTC)

Unsourced 1
moved the following here per WP:PRESERVE. Per WP:BURDEN, please do not restore without finding reliable sources, checking the content against them, and citing them. Please note that secondary sources are needed - please don't cite the paper itself where things were first published -those papers cannot be the source that they were first or where the "dicovery" per se was published. Another source needs to say that.

In 1932, Jean La Barre introduced the word incretin, acronym of intestine secretion insulin, for a purified hypoglycaemia-inducing substance extracted from the upper gut mucosa. Furthermore, La Barre emphasised the potential of incretin for treatment of diabetes patients.
 * Discovery

In 1970, John C. Brown et al. isolated a peptide from porcine intestinal extracts, potent of inhibiting gastric acid secretion and accordingly named gastric inhibitory polypeptide (GIP). A few years later, John Dupre et al. demonstrated that GIP was an incretin as intravenously infused porcine GIP significantly augmented insulin secretion in a glucose-dependent manner in both animals and humans and it was renamed glucose-dependent insulinotropic polypeptide.

In 1983, Reinhold Elbert et al. demonstrated that rats depleted of GIP by radioadsorption preserved more than 50 % of the incretin effect, suggesting the existence of an additional incretin. Around this time, Pauline Kay Lund et al. cloned and sequenced the proglucagon gene in the anglerfish and found that in addition to glucagon, other smaller peptides were also encoded within the gene. Interestingly, two of the peptides shared approximately 50 % homology to glucagon and was accordingly named glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). Due to their homology to glucagon both peptides were tested for insulinotropic activity, where only GLP-1 was found capable of stimulating insulin secretion, thus becoming the second identified incretin.

-- Jytdog (talk) 19:13, 7 May 2017 (UTC)

unsourced 2
the following is all unsourced. moved here per WP:PRESERVE. Per [{WP:BURDEN]], please do not restore without finding reliable sources per RS or MEDRS as is relevant, checking the content against them, and citing them.


 * Pancreatic Effects


 * increases insulin secretion in a glucose-dependent manner
 * increases insulin gene transcription, mRNA stability and biosynthesis
 * decreases glucagon secretion predominantly through promotion of somatostatin secretion
 * increases β cell mass by promoting proliferation and neogenesis and inhibiting apoptosis.
 * increases glucose sensitivity of β cells

The most noteworthy effect of GLP-1 is its ability to promote insulin secretion in a glucose-dependent manner. As GLP-1 binds to GLP-1 receptors expressed on the pancreatic β cells, the receptors couples to G-protein subunits and activates adenylate cyclase that increases the production of cAMP from ATP. Subsequently, activation of secondary pathways, including PKA and Epac2, alters the ion channel activity causing elevated levels of cytosolic Ca2+ that enhances exocytosis of insulin-containing granules. During the process, influx of glucose ensures sufficient ATP to sustain the stimulatory effect.

Additionally, GLP-1 ensures the β cell insulin stores are replenished to prevent exhaustion during secretion by promoting insulin gene transcription, mRNA stability and biosynthesis. In response to the rising cAMP levels, cAMP element-binding protein (CREB) binds to a cAMP responsive element on the promoter region of the insulin gene to upregulate the transcription. Transcription factors including pancreas and duodenal homeobox 1 (PDX-1) and nuclear factor of activated T (NFAT) has also been linked with this upregulation.

GLP-1 also upregulates the expression of glucose transports, glucokinase, KATP channel subunit Kir6.2 and sulphonylurea receptor 1 (SUR1), all of which improves the ability of β cells to sense and response to glucose.

GLP-1 evidently also increases β cell mass by promoting proliferation and neogenesis while inhibiting apoptosis. As both type 1 and 2 diabetes are associated with reduction of functional β cells, this effect is highly interesting regarding diabetes treatment. Upon receptor activation, a signalling cascade is initiated that involves different pathways in which the activation of PDX-1 expression plays a central role. Alternative proliferation promoting pathway that terminates at extracellular signal-regulated kinase (ERK) has also been identified. Furthermore, another pathway is associated with the transactivation of the epidermal growth factor receptor (EGFR) which initiates a signalling cascade terminating with the inhibition of caspase-3, an enzyme responsible for apoptosis execution.

Considered almost as important to the insulin secretion effects, GLP-1 has shown to inhibit glucagon secretion at glucose levels above fasting levels. Critically, this does not affect the glucagon response to hypoglycaemia as this effect is also glucose-dependent. The inhibitory effect is presumably mediated indirectly through somatostatin secretion, but a direct effect can not be completely excluded.


 * Extrapancreatic effects


 * increases neuronal cell mass by promoting proliferation and neogenesis and inhibition of apoptosis
 * decrease food intake by promoting satiety and inhibiting appetite
 * inhibit gastric emptying, acid secretion and motility
 * promote lipogenesis and adipogenesis
 * increases glucose uptake in adipose tissue and muscles
 * increase bone formation and decrease bone resorption by promoting calcitonin
 * increases cardiac function
 * also likely modulates immune system activity

In the brain, GLP-1 has been linked with neurotropic effects including proliferation, neogenesis and anti-apoptosis. This protective behaviour has shown to increase both memory and learning functions. In accordance with the expression of GLP-1 receptor on brainstem and hypothalamus, GLP-1 has shown to promote satiety and thereby reduce food and water intake. Consequently, diabetic subjects treated with GLP-1 receptor agonists often experience weight loss as opposed to the weight gain commonly induced with other treatment agents.

In the stomach, GLP-1 inhibits gastric emptying, acid secretion and motility collectively decreasing appetite. By decelerating gastric emptying GLP-1 reduce postprandial glucose excursion which is another attractive property regarding diabetes treatment. However, these gastrointestinal activities are also the reason why subjects treated with GLP-1-based agents occasionally experience nausea.

Besides stimulating the release of insulin to lower the blood sugar level, GLP-1 is also associated with an anabolic effect on adipose tissue including lipogenesis and adipogenesis and enhancement of glucose uptake in adipose tissue.

In patients with heart injuries, GLP-1 has shown to act protectively against myocardial ischemia and reduce infarct sizes. Interestingly, the DPP-4 degraded metabolite, GLP-1(9-36)amide has been suggested to be the active peptide in regards to the cardiovascular effects.

GLP-1 has also been associated with upregulation of calcitonin, a peptide hormone regulating Ca2+ levels in the blood by inhibiting bone resorption and stimulating bone formation.

In muscles, GLP-1 has shown potent of recruiting muscle microvasculature and stimulate muscle glucose uptake independent of its insulinotropic effect.

Considering the expression of GLP-1 receptors in lungs, it has been suggested that GLP-1 might exert anti-inflammatory effects in the lungs.

Some studies also suggest that GLP-1 enhances glucose clearance, whereas others suggest that GLP-1 simply inhibits the hepatic glucose production.

The physiological role of renal GLP-1 receptors remains unclear, but rodent studies have suggested a renoprotective potential.

-- Jytdog (talk) 04:13, 3 August 2017 (UTC)