Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long
peptide hormone
Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...
deriving from the tissue-specific posttranslational processing of the
proglucagon peptide. It is produced and secreted by intestinal
enteroendocrine L-cells and certain neurons within the nucleus of the
solitary tract
The solitary tract (tractus solitarius, or fasciculus solitarius), is a compact fiber bundle that extends longitudinally through the posterolateral region of the medulla oblongata. The solitary tract is surrounded by the solitary nucleus, and des ...
in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to
amidation
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is p ...
and
proteolytic cleavage
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...
, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1
protein secondary structure includes two
α-helices
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...
from amino acid position 13–20 and 24–35 separated by a linker region.
Alongside
glucose-dependent insulinotropic peptide (GIP), GLP-1 is an
incretin
Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-gl ...
; thus, it has the ability to decrease
blood sugar levels in a glucose-dependent manner by enhancing the
secretion of
insulin. Beside the insulinotropic effects, GLP-1 has been associated with numerous regulatory and protective effects. Unlike GIP, the action of GLP-1 is preserved in patients with
type 2 diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...
and substantial pharmaceutical research has therefore been directed towards the development of GLP-1-based treatment.
Endogenous GLP-1 is rapidly degraded primarily by
dipeptidyl peptidase-4
Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the ''DPP4'' gene. DPP4 is related to FAP, DPP8, and DPP9. The enzyme was ...
(DPP-4), as well as neutral endopeptidase 24.11 (NEP 24.11) and
renal clearance, resulting in a
half-life
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
of approximately 2 minutes. Consequently, only 10–15 % of GLP-1 reaches circulation intact, leading to fasting plasma levels of only 0–15 pmol/L. To overcome this,
GLP-1 receptor agonists and
DPP-4 inhibitors
Inhibitors of dipeptidyl peptidase 4 (DPP-4 inhibitors or gliptins) are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4). They can be used to treat diabetes mellitus type 2.
The first agent of the class – sitag ...
have been developed to increase GLP-1 activity. As opposed to common treatment agents such as
insulin and
sulphonylurea, GLP-1-based treatment has been associated with
weight loss
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...
and a lower risk of
hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...
, two important considerations for patients with type 2 diabetes.
Gene expression
The proglucagon gene is expressed in several organs including the
pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an en ...
(
α-cells of the
islets of Langerhans
The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of ...
), gut (intestinal enteroendocrine L-cells) and
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
(caudal
brainstem and
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
). Pancreatic proglucagon gene expression is promoted upon fasting and hypoglycaemia induction and inhibited by insulin. Conversely, intestinal proglucagon gene expression is reduced during fasting and stimulated upon food consumption. In mammals, the transcription gives rise to identical
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
in all three cell types, which is further translated to the 180 amino acid precursor called
proglucagon. However, as a result of tissue-specific posttranslational processing mechanisms, different peptides are produced in the different cells.
In the
pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an en ...
(
α-cells of the
islets of Langerhans
The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of ...
),
proglucagon is cleaved by
prohormone convertase Proprotein convertases (PPCs) are a family of proteins that activate other proteins. Many proteins are inactive when they are first synthesized, because they contain chains of amino acids that block their activity. Proprotein convertases remove thos ...
(PC) 2 producing glicentin-related pancreatic peptide (GRPP),
glucagon, intervening peptide-1 (IP-1) and major proglucagon fragment (MPGF).
In the gut and brain,
proglucagon is catalysed by PC 1/3 giving rise to glicentin, which may be further processed to GRPP and
oxyntomodulin Oxyntomodulin (often abbreviated OXM) is a naturally occurring 37-amino acid peptide hormone found in the colon, produced by the oxyntic (fundic) cells of the oxyntic (fundic) mucosa. It has been found to suppress appetite.
The mechanism of actio ...
, GLP-1, intervening peptide-2 (IP-2) and
glucagon-like peptide-2 (
GLP-2 Glucagon-like peptide-2 (GLP-2) is a 33 amino acid peptide with the sequence HADGSFSDEMNTILDNLAARDFINWLIQTKITD (see Proteinogenic amino acid) in humans. GLP-2 is created by specific post-translational proteolytic cleavage of proglucagon in a process ...
). Initially, GLP-1 was thought to correspond to proglucagon (72–108) suitable with the
N-terminal of the MGPF, but sequencing experiments of endogenous GLP-1 revealed a structure corresponding to proglucagon (78–107) from which two discoveries were found. Firstly, the full-length GLP-1 (1–37) was found to be catalysed by
endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids (i.e. within the molecule), in contrast to exopeptidases, which break peptide bonds from end-pieces of terminal amino acids. For this ...
to the biologically active GLP-1 (7–37). Secondly, the
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
corresponding to proglucagon(108) was found to serve as a substrate for
amidation
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is p ...
of the
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
arginine resulting in the equally potent GLP-1 (7–36) amide. In humans, almost all (>80%) secreted GLP-1 is amidated, whereas a considerable part remains GLP-1 (7–37) in other species.
Secretion
GLP-1 is packaged in secretory granules and secreted into the
hepatic portal system
In human anatomy, the hepatic portal system is the system of veins comprising the hepatic portal vein and its tributaries. It is also called the portal venous system (although it is not the only example of a portal venous system) and splanchnic ...
by the intestinal L-cells located primarily in the distal
ileum
The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine m ...
and colon, but also found in the
jejunum
The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previou ...
and
duodenum. The L-cells are open-type triangular
epithelial cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
directly in contact with the
lumen and neuro-vascular tissue and are accordingly stimulated by various
nutrient,
neural and
endocrine factors.
GLP-1 is released in a
biphasic
Biphasic, meaning having two phases, may refer to:
* Phase (matter)
In the physical sciences, a phase is a region of space (a thermodynamic system), throughout which all physical properties of a material are essentially uniform. Examples ...
pattern with an early phase after 10–15 minutes followed by a longer second phase after 30–60 minutes upon meal ingestion. As the majority of L-cells are located in the distal
ileum
The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine m ...
and colon, the early phase is likely explained by neural signalling, gut peptides or
neurotransmitters
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurot ...
. Other evidence suggest that the amount of L-cells located in the proximal
jejunum
The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previou ...
is sufficient to account for the early phase secretion through direct contact with luminal nutrients. Less controversially, the second phase is likely caused by direct stimulation of L-cells by digested
nutrients
A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excre ...
. The rate of
gastric emptying is therefore an important aspect to consider, as it regulates the entry of nutrients into the
small intestines
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the pa ...
where the direct stimulation occurs. One of the actions of GLP-1 is to inhibit
gastric emptying, thus slowing down its own
secretion upon
postprandial
Prandial relates to a meal. Postprandial (from post prandium) means after eating a meal, while preprandial is before a meal.
Usages of postprandial
The term ''postprandial'' is used in many contexts.
Gastronomic or social
Refers to activities p ...
activation.
Fasting plasma concentration of biologically active GLP-1 range between 0 and 15 pmol/L in humans and is increased 2- to 3-fold upon food consumption depending on meal size and nutrient composition. Individual nutrients, such as
fatty acids
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an B ...
,
essential amino acids
An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...
and
dietary fibre
Dietary fiber (in British English fibre) or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition, and can be grouped generally by th ...
have also shown to stimulate GLP-1 secretion.
Sugars
Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...
have been associated with various
signalling pathways, which initiate
depolarisation
In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...
of the L-cell membrane causing an elevated concentration of
cytosolic
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
Ca
2+ which in turn induce GLP-1 secretion.
Fatty acids
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an B ...
have been associated with the mobilisation of
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
Ca
2+ stores and subsequently release of Ca
2+ into the
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
. The mechanisms of protein-triggered GLP-1 secretion are less clear, but the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
proportion and composition appear important to the stimulatory effect.
Degradation
Once secreted, GLP-1 is extremely susceptible to the catalytic activity of the proteolytic enzyme
dipeptidyl peptidase-4
Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the ''DPP4'' gene. DPP4 is related to FAP, DPP8, and DPP9. The enzyme was ...
(
DPP-4). Specifically,
DPP-4 cleaves the
peptide bond between Ala
8-Glu
9 resulting in the abundant GLP-1 (9–36) amide constituting 60–80 % of total GLP-1 in circulation.
DPP-4 is widely expressed in multiple tissues and cell types and exists in both a membrane-anchored and soluble circulating form. Notably,
DPP-4 is expressed on the surface of
endothelial cells
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
, including those located directly adjacent to GLP-1 secretion sites.
Consequently, less than 25% of secreted GLP-1 is estimated to leave the gut intact. Additionally, presumably due to the high concentration of
DPP-4 found on
hepatocytes
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, ...
, 40–50% of the remaining active GLP-1 is degraded across the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
. Thus, due to the activity of
DPP-4 only 10–15 % of secreted GLP-1 reaches circulation intact.
Neutral endopeptidase 24.11 (NEP 24.11) is a membrane-bound zinc metallopeptidase widely expressed in several tissues, but found in particularly high concentrations in the
kidneys
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
, which is also identified accountable for the rapid degradation of GLP-1. It primarily cleaves peptides at the
N-terminal side of
aromatic amino acids or
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, t ...
amino acids and is estimated to contribute by up to 50% of the GLP-1 degradation. However, the activity only becomes apparent once the degradation of
DPP-4 has been prevented, as the majority of GLP-1 reaching the
kidneys
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
have already been processed by
DPP-4. Similarly,
renal clearance appear more significant for the elimination of already inactivated GLP-1.
The resulting
half-life
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
of active GLP-1 is approximately 2 minutes, which is however sufficient to activate GLP-1 receptors.
Physiological functions
GLP-1 possesses several physiological properties making it (and its
functional analogs) a subject of intensive investigation as a potential treatment of
diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, as these actions induce long-term improvements along with the immediate effects. Although reduced GLP-1 secretion has previously been associated with attenuated incretin effect in patients with
type 2 diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...
, it is now granted that GLP-1 secretion in patients with type 2 diabetes does not differ from healthy subjects.
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
Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction:
:A ...
that increases the production of
cAMP
Camp may refer to:
Outdoor accommodation and recreation
* Campsite or campground, a recreational outdoor sleeping and eating site
* a temporary settlement for nomads
* Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
from
ATP.
Subsequently, activation of secondary pathways, including PKA and
Epac2, alters the ion channel activity causing elevated levels of cytosolic Ca
2+ 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
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
stability and biosynthesis.
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.
Considered almost as important as the effect of enhancing insulin secretion, GLP-1 has been shown to inhibit glucagon secretion at glucose levels above fasting levels. Critically, this does not affect the glucagon response to
hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...
as this effect is also glucose-dependent. The inhibitory effect is presumably mediated indirectly through
somatostatin secretion, but a direct effect cannot be completely excluded.
In the brain, GLP-1 receptor activation has been linked with neurotrophic effects including
neurogenesis and
neuroprotective
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...
effects including reduced necrotic
and apoptotic
signaling,
cell death
Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as d ...
, and dysfunctions. In the diseased brain, GLP-1 receptor agonist treatment is associated with protection against a range of experimental disease models such as
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
,
Alzheimer's disease, stroke,
traumatic brain injury
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic br ...
,
and
multiple sclerosis.
In accordance with the expression of GLP-1 receptor on brainstem and hypothalamus, GLP-1 has been 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, which collectively decrease appetite. By decelerating gastric emptying GLP-1 reduces 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
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
.
GLP-1 has also shown signs of carrying out protective and regulatory effects in numerous other tissues, including heart, tongue, adipose, muscles, bones, kidneys, liver and lungs.
See also
*
Glucagon-like peptide 1 receptor
*
Glucagon-like peptide-2
*
Type 2 diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...
*
GLP-1 analogs :
exenatide
Exenatide, sold under the brand name Byetta and Bydureon among others, is a medication used to treat diabetes mellitus type 2. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after ...
,
liraglutide
Liraglutide, sold under the brand name Victoza among others, is an anti-diabetic medication used to treat type 2 diabetes, obesity, and chronic weight management. In diabetes it is a less preferred agent compared to metformin. Its effects on l ...
,
dulaglutide
Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardiov ...
,
semaglutide
*
Dipeptidyl peptidase-4
Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the ''DPP4'' gene. DPP4 is related to FAP, DPP8, and DPP9. The enzyme was ...
*
Glucose-dependent insulinotropic peptide
References
External links
*
*
Insulin release pathways
American diabetes association:link-http://diabetes.diabetesjournals.org/content/56/1/8.full
{{DEFAULTSORT:Glucagon-Like Peptide-1
Anti-diabetic drugs
Diabetes
Peptide hormones