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DIABETES
PEPTIDES
Peptides and Diabetes PEPTIDES FOR
DIABETES RESEARCH

According to data from the International Diabetes Federa-tion, more than 250 million people around the world suf-fer from diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia. Diabetes mellitus can be divided into two main types, type 1 or insulin-dependent diabetes mellitus (IDDM) and type 2, or non insulin-depen-dent diabetes mellitus (NIDDM). The absolute lack of insu-lin, due to destruction of the insulin producing pancreatic β-cells, is the particular disorder in type 1 diabetes. Type 2 diabetes is mainly characterized by the inability of cells to respond to insulin. The condition affects mostly the cells of muscle and fat tissue, and results in a condition known as „insulin resistance".
means ‘to fl ow through'. The adjective mel- Diabetes was already known in ancient litus, which comes from Latin and means times. The name of this disease was created ‘honey-sweet', was added by the German by the Graeco-Roman physician Aretaeus physician Johann Peter Frank (1745-1821). of Cappadocia (approx. 80 - 130 AD) and is It was introduced in order to distinguish di- derived from the Greek word diabainein that abetes mellitus, also called ‘sugar diabetes', from diabetes insipidus, where an exces-sive amount of urine is produced as a result of a disturbance of the hormonal control of reabsorption of water in the kidneys. In 1889, pancreatic secretions were shown EFFECTS OF
to control blood sugar levels. However, it took another 30 years until insulin was purifi ed from the islets of Langerhans. In the following 50 years scientists detected Over time, diabetes mellitus can lead the system-wide effects of insulin in liver, to blindness, kidney failure, and nerve muscle, and adipose tissues. In the 1970s, damage. Diabetes mellitus is also an the insulin receptor was discovered, and 10 important factor in accelerating the years later, its tyrosine kinase activity was hardening and narrowing of the arter- demonstrated. Despite this steady prog- ies (atherosclerosis), leading to stroke, ress, one of the most challenging health coronary heart diseases, and other problems of the 21st century remains the blood vessel disorders.
dramatic increase in diabetes mellitus that is occurring throughout the world. Today fi de bridge) linked by two disulfi de bridges Glucose homeostasis
diabetes mellitus is one of the main causes to a B-chain of 30 amino acids. β-Cells is accomplished by
of death in most developed countries.
secrete insulin in response to a rising level complex physiological
mechanisms. Control

According to data from the International of circulating glucose. The normal fasting of blood glucose levels
Diabetes Federation, more than 250 mil- blood glucose concentration in humans and involves insulin, gluca-
lion people around the world suffer from most mammals is 80 to 90 mg per 100 ml, gon and other peptide
diabetes and this number will grow to more associated with very low levels of insulin hormones such as
than 380 millions by 2030. Further 300 secretion. After a meal, excess sugars must glucagon-like peptide
million people have impaired glucose toler- be stored so that energy reserves will be 1 (GLP-1) and glucose-
ance, a condition that can signal oncoming available later on. Excess glucose is sensed dependent insulinotro-
pic polypeptide (gastric

diabetes. More than 90% of the diabetics by β-cells in the pancreas, which respond inhibitory polypeptide
have type 2 diabetes, a chronic disease as- by secreting insulin into the bloodstream.
sociated with insulin defi ciency and insulin Insulin causes various cells in the body to resistance. Complications seen with diabe- store glucose (see Fig. 1): tes range from heart disease (2 to 4 times • Insulin stimulates skeletal muscle fi bers higher occurence than in non-diabetics) to convert glucose into glycogen. It also in- to blindness, kidney disease, amputations, duces the synthesis of proteins from amino nerve damage and erectile dysfunction. acids circulating in the blood.
As obesity spreads, the number of type 2 • Insulin acts on liver cells. It stimulates diabetics rises. Over 80% of diabetics are them to take up glucose from the blood obese. Consequently, the treatment of risk converting it into glycogen while inhibiting factors such as obesity, hypertension, and the production of the enzymes involved in hyperlipidemia assumes major impor- tance and must be coordinated with a good • Insulin acts on fat cells to stimulate the glycemic control for the reduction in total uptake of glucose and the synthesis of fat.
mortality in type 2 diabetes mellitus. In this In each case, insulin triggers these effects monograph, we describe the pancreatic and by binding to the insulin receptor, a hetero- gastrointestinal peptide hormones that are tetramer of two extracellular α-subunits involved in the control of blood glucose, the that are bonded by disulfi des to two trans- classifi cation, and the treatment of diabe- membrane β-subunits. Insulin receptor tes mellitus.
activation leads to specifi c phosphorylation events followed by an increase in glucose Pancreatic Peptide Hormones
storage and a concomitant decrease in The islets of Langerhans contain four main hepatic glucose release.
cell types: β-cells secreting insulin, α-cells C-Peptide is applied as a diagnostic tool. It secreting glucagon, δ-cells secreting is released in amounts equal to insulin, so somatostatin and γ-cells secreting pancre- the level of C-peptide in the blood indicates atic polypeptide (PP). The core of each islet how much insulin is being produced by the contains mainly the β-cells surrounded pancreas. The concentration of C-peptide is by a mantle of α-cells interspersed with measured in diabetics to differentiate be- δ-cells or γ-cells. Insulin is synthesized as a tween endogenous (produced by the body) preprohormone in the β-cells of the islets of and exogenous (injected into the body) Langerhans. Removal of its signal peptide insulin, since synthetic insulin does not during insertion into the endoplasmic retic- contain the C-peptide. Inappropriate use ulum generates proinsulin which consists of insulin in persons with a low blood sugar of 3 domains: an amino-terminal B-chain, a level results in a low C-peptide level. The carboxy-terminal A-chain and a connecting C-peptide level can also be determined in peptide known as C-peptide. Within the en- patients with type 2 diabetes showing how doplasmic reticulum proinsulin is exposed much insulin is produced by the β-cells. to several specifi c endopeptidases. These Abnormal high amounts of C-peptide can enzymes excise the C-peptide, thereby indicate the presence of a tumor called generating the mature form of insulin, a insulinoma which secretes insulin.
small protein consisting of an A-chain of 21 β-Cells also secrete a peptide hormone amino acids (containing an internal disul- known as islet amyloid polypeptide (IAPP) Peptides and Diabetes Promotes insulin release
Stimulates breakdown of glycoge
Stimulates formation of glycogen
Stimulation of glucose uptake
from blood
Tissue cells
(muscle, kidney, fat)

Opposing effects of insulin and glucagon or amylin. This 37 amino acid peptide is Fig. 1). It counterbalances the action of in- structurally related to calcitonin and has sulin, increasing the levels of blood glucose weak calcitonin-like effects on calcium and stimulating the protein breakdown metabolism and osteoclast activity. Amylin in muscle. Glucagon is a major catabolic shows about 50% sequence identity with hormone, acting primarily on the liver. The calcitonin gene-related peptide (CGRP). It is peptide stimulates glycogenolysis (glycogen stored together with insulin in the secre- breakdown) and gluconeogenesis (syn- tory granules of β-cells and is co-secreted thesis of glucose from non-carbohydrate with insulin. Amylin's most potent actions sources), inhibits glycogenesis (glycogen include the slowing of gastric emptying and synthesis) and glycolysis, overall increas- the suppression of postprandial glucagon ing hepatic glucose output and ketone body secretion. The hormone also reduces food formation. In people suffering from diabe- intake and inhibits the secretion of gastric tes, excess secretion of glucagon plays a acid and digestive enzymes.
primary role in hyperglycemia (high blood Thus, there is therapeutic potential of IAPP glucose concentration). Glucagon is clini- agonists for the treatment of patients with cally used in the treatment of hypoglycemia absolute amylin defi ciency (type 1 diabe- in unconscious patients (who can't drink).
tes) or relative amylin defi ciency (type 2 Somatostatin release from the pancreas and gut is stimulated by glucose and amino In addition, amylin is the major component acids. In diabetes, somatostatin levels are of the pancreatic amyloid deposits occur- increased in pancreas and gut, presum- ring in the pancreas of patients with type 2 ably as a consequence of insulin defi ciency. Somatostatin inhibits secretion of growth Glucagon secretion is stimulated by low, hormone, insulin and glucagon.
and inhibited by high concentrations of glucose and fatty acids in the plasma (see Gastrointestinal Peptide Hormones
Glucose-dependent insulinotropic poly-
peptide (GIP) and glucagon-like peptide 1 (GLP-1) have signifi cant effects on insulin secretion and glucose regulation. They are Post-translational released after ingestion of carbohydrate- and fat-rich meals and stimulate insulin se-cretion postprandially. Both gut hormones constitute the class of incretins and share considerable sequence homology. GIP is a single 42 amino acid peptide derived from a larger 153 amino acid precursor (see Fig. 2).
The peptide was originally observed to inhibit gastric acid secretion (hence it was the circulating GLPs.
Fig. 2.
Structure of prepro-GIP
designated gastric inhibitory polypeptide). The primary physiological responses to Subsequent studies have demonstrated po- GLP-1 are glucose-dependent insulin tent glucose-dependent insulin stimulatory secretion, inhibition of glucagon secretion effects of GIP administration in dogs and and inhibition of gastric acid secretion and rodents. GIP also regulates fat metabolism gastric emptying. All effects of GLP-1 are in adipocytes, including stimulation of lipo- exerted by activation of the GLP-1 receptor, protein lipase activity, fatty acid incorpora- a seven transmembrane spanning G- tion, and fatty acid synthesis. Unlike GLP-1, protein-coupled receptor (GPCR), leading to GIP does not inhibit glucagon secretion or increased cAMP production and enhanced gastric emptying. The peptide promotes protein kinase A (PKA) activity.
β-cell proliferation and cell survival in islet The potential use of GLP-1 for the treatment Structure of preproglu-cagon: GRPP, glicentin- cell line studies.
of diabetes has been considered. GLP-1 ex- related pancreatic GLP-1 is derived from the product of the erts antidiabetogenic properties in subjects peptide; IP, intervening proglucagon gene. This gene encodes a with type 2 diabetes by stimulating insulin peptides. Further pep- preproprotein (see Fig. 3) that is differen- secretion, increasing β-cell mass, inhibit- tides derived from the tially processed dependent on the tissue in ing glucagon secretion, delaying gastric preproprotein include which it is expressed. In pancreatic α-cells, emptying, and inducing satiety, thus slowing glicentin which is com- prohormone convertase 2 action leads to the entry of sugar into the blood. However, posed of amino acids 1-69, oxyntomodulin the release of glucagon. In the gut, prohor- GLP-1 is rapidly degraded by the enzyme (glucagon-37) consisting mone convertase 1/3 action leads to the dipeptidyl peptidase IV (DPP IV), making it of amino acids 33-69, release of several peptides including GLP- unattractive as a therapeutic agent.
and the major proglu- 1. Bioactive GLP-1 consists of two forms: Successful strategies to overcome this dif- cagon fragment (MPGF) GLP-1 (7-37) and GLP-1 (7-36) amide. The fi culty are the use of DPP IV-resistant GLP-1 comprising amino acids latter form constitutes the majority (80%) of receptor agonists, such as NN2211 (lira- Post-translational GLP-1 (7-36) amide Peptides and Diabetes glutide, a fatty acid-linked DPP IV-resistant insulin-dependent diabetes mellitus or derivative of GLP-1) or exendin-4 (exena- maturity-onset diabetes) is associated with tide). An alternative approach is the use insulin resistance rather than the lack of of inhibitors of DPP IV, such as sitagliptin, insulin as seen in type 1 diabetes. This lack P32/98 (H-Ile-thiazolidide hemifumarate), of insulin sensitivity results in higher than normal blood glucose levels.
amino)ethyl]-Gly-Pro-nitrile) and the Gly- Type 2 diabetes is not HLA-linked and no Pro-nitrile-derived compounds vildagliptin autoimmune destruction of the pancre- and saxagliptin.
atic cells is observed. The development of Exendin-4 is a peptide hormone found type 2 diabetes seems to be multifacto- in the saliva of the Gila monster, a lizard rial. Genetic predisposition appears to be native to several Southwestern American the strongest factor. Other risk factors are states. Like GLP-1 exendin-4 exerts its obesity and high caloric intake. Pancre- effects through the GLP-1 receptor but is atic α-cell mass is increased, followed by much more potent than GLP-1. Exenatide, an exaggerated response of glucagon to a synthetic form of exendin-4 has been ap- amino acids and an impaired suppression proved by the FDA as an antidiabetic drug. of glucagon secretion by hyperglycemia. In contrast to most drugs that work by only Increased hepatic production of glucose one mechanism, exendin-4 acts by multiple with a failure of the pancreas to adapt to mechanisms, such as stimulation of insulin this situation and resistance to the action secretion, slowing gastric emptying, and of insulin are characteristic features of this inhibiting the production of glucose by the disorder. Another important morphological liver. Furthermore, exendin-4 was shown to feature is the amyloid deposition in islets. suppress appetite and promote weight loss.
These deposits consist of islet amyloid polypeptide or amylin, that is believed, to Classifi cation of Diabetes Mellitus
originate in the β-cell secretory granule.
The American Diabetes Association distin- Type 2 diabetes occurs most frequently guishes between two main types of dia- in adults, but is being noted increasingly betes mellitus. This division is based upon in adolescents as well. Type 2 diabetes whether the ‘blood sugar problem‘ is caused develops slowly and the symptoms are by insulin defi ciency or insulin resistance: usually less severe than in type 1. Some- Type 1 diabetes (formerly known as insulin- times the disease is only diagnosed several dependent diabetes mellitus or juvenile- years after its onset, when complications onset diabetes) is a β-islet cell specifi c, are already present. Common late micro- T-lymphocyte-mediated autoimmune vascular complications include retinopathy, disorder. It is characterized by a failure of nephropathy, and peripheral and autonomic the pancreas to produce suffi cient insulin. neuropathies. Macrovascular complications Without insulin to promote the cellular up- include atherosclerotic coronary peripheral take of glucose, the blood glucose concen- arterial disease.
trations reach high levels. At concentrations above 10 mM, renal tubular reabsorption Treatment of Diabetes Mellitus
is saturated and glucose is passed into the Insulin is essential for the treatment of type urine. The classic symptoms are excessive 1 diabetes. The effects of insulin and its secretion of urine, thirst, weight loss and mechanism of action are described above. For clinical application, either porcine or It is known that multiple genes contribute bovine insulin was given formerly. Today, to the familial clustering of this disease, the human insulin (produced recombinantly) is major histocompatibility complex (MHC) used. A new approach is the production of being the most important of these. The orally active insulin using modifi cations to MHC class 2 genotype is one of the stron- make insulin resistant to enzymatic break- gest genetic factors determining disease down, facilitating absorption.
Most of the vascular consequences of insu- Type 2 diabetes (formerly named non- lin resistance are due to the hyperglycemia seen in type 2 diabetes. For this reason a most widely prescribed insulin-sensitizing Advances in genomics,
major goal of therapeutic intervention in drug in clinical use. The major site of ac- proteomics and me-
type 2 diabetes is to reduce circulating glu- tion for metformin is the liver. Its use can tabolomics will help us
to further understand

cose levels. There are many pharmacologi- be contraindicated in patients with liver the causes of type 1
cal strategies to accomplish these goals: and type 2 diabetes and
1) The use of α-glucosidase inhibitors (e.g. 4) The thiazolidinediones (e.g. pioglitazone) might eventually lead
acarbose) leads to a reduction in digestion have been proven useful in treating the to novel therapeutic
and thereby minimizes the consequent hyperglycemia associated with insulin absorption of glucose into the systemic resistance in both type 2 diabetes and circulation. The reduction in glucose uptake non-diabetic conditions. These products allows the pancreatic β-cells to regulate function as agonists for the peroxisome the insulin secretion more effectively. The proliferator-activated receptor-γ (PPAR-γ). advantage of α-glucosidase inhibitors is PPARs are members of a nuclear receptor that they function locally in the intestine superfamily that has important roles in car- and have no major systemic action. Plants bohydrate and lipid metabolism. Thiazoli- are rich sources of α-glucosidase inhibitors, dinediones enhance peripheral sensitivity some of which are being evaluated for their to insulin and, to a lesser degree, decrease hepatic glucose production by binding to 2) The sulfonylureas (e.g. glibenclamide) and activating the PPAR-γ. Adverse effects are referred to as endogenous insulin se- of thiazolidine-diones include weight gain, cretagogues because they induce the pan- anemia, and abnormalities in liver and en- creatic release of insulin and thus reduce zyme levels. Resistin, an adipocyte-derived plasma glucose. Sulfonylureas function peptide, fi rst identifi ed during a search by binding to and inhibiting the pancre- for targets of thiazolidinediones, has been atic ATP-dependent potassium channels found to be downregulated by thiazolidin- normally involved in the glucose-mediated insulin secretion. Unwanted side-effects 5) GLP-1 analogs stimulate insulin release, of sulfonylureas are appetite stimulation, inhibit glucagon secretion, slow gastric probably via their effects on insulin secre- emptying and stimulate β-cell proliferation. tion and blood glucose, often leading to One of the most promising GLP-1 receptor weight gain.
agonists is exenatide (exendin-4) which is 3) The biguanides (e.g. metformin) are a 53% identical to human GLP-1 at the amino class of drugs that lower blood glucose acid level. The main advantage of exenatide levels by enhancing insulin-mediated is its resistance to cleavage and inactiva- suppression of hepatic glucose produc- tion by dipeptidyl-peptidase IV (DPP IV). The tion (gluconeogenesis) and by enhanc- FDA has approved exenatide as adjunctive ing insulin-stimulated glucose uptake by therapy to improve blood sugar control in skeletal muscle. Metformin is currently the patients with type 2 diabetes who have not MORE THAN 250 MILLION PEO-
PLE AROUND THE WORLD SUF-
FER FROM DIABETES AND THIS
NUMBER WILL GROW TO MORE
THAN 380 MILLIONS BY 2030

Peptides and Diabetes achieved adequate control with metformin and/or a sulfonylurea. A sustained release Although some of the agents described formulation is currently awaiting FDA ap- above are still in the early phases of investi- gation, there is little doubt that the therapy The long-acting GLP-1 agonist liraglutide of diabetes will undergo major changes in was approved by the same authority for the the near future. It is important to diagnose treatment of type 2 diabetes in 2010.
all type 2 diabetics at an earlier stage (for 6) DPP IV inhibitors represent another example by making self monitoring of blood approach for the treatment of diabetes. Si- glucose easier) and begin treatment in an tagliptin is the fi rst candidate of this novel attempt to minimize the diabetes-associat- class of antihyperglycemic agents that ed complications.
has been approved by the FDA. Linagliptin, The identifi cation of the genetic com- saxagliptin, and vildagliptin have been ap- ponents of type 1 and type 2 diabetes is proved as well in various countries world- an important area of research, because wide. These DPP IV inhibitors can be used elucidation of the diabetes genes will infl u- either alone or in combination with other ence all efforts towards an understanding oral antihyperglycemic agents (such as of the disease, its complications, and its metformin or a thiazolidinedione) for treat- treatment, cure, and prevention. Recently, ment of diabetes mellitus type 2.
genomic DNA from subjects with severe 7) Pramlintide, a soluble amylin analog, has insulin resistance has been screened for gained FDA approval as an adjunct to in- mutations in genes that are implicated in sulin therapy in type 1 and type 2 diabetes. insulin signaling. Thereby, a mutation in the Like amylin it acts centrally and decreases gene encoding the serine/threonine kinase glucagon secretion, slows gastric emptying AKT2 (also known as PKBβ) was identifi ed. and induces satiety.
AKT2 is highly expressed in insulin-sensi- 8) Insulin therapy is also indicated in tive tissues and has been implicated in in- the treatment of type 2 diabetes for the sulin-regulated glucose uptake into muscle management of severe hyperglycemia after and fat cells by promoting the translocation failure of oral agents.
of glucose transporter 4 (GLUT4) to the cell 9) C-Peptide is biologically active. Recent clinical studies showed that administration Advances in genomics, proteomics and of C-peptide to diabetes type 1 patients metabolomics will help us to further un- lacking the peptide alleviates nerve and derstand the causes of type 1 and type 2 renal dysfunctions associated with the diabetes and might eventually lead to novel R.J. Mahler and M.L. Adler
J.M. Egan et al.
In the 1970s, the insulin
Clinical Review 102: Type 2 diabe- GLP-1 receptor agonists are growth receptor was discov-
tes mellitus: update on diagnosis, and differentiation factors for pan- ered, and 10 years
later, its tyrosine kinase

pathophysiology, and treatment.
creatic islet beta cells.
activity was demon-
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J.J. Holst
GIP or not GIP? That is the question.
Gastric inhibitory polypeptide ana- Trends Pharmacol. Sci. 24, 110-112 logues: do they have a therapeutic role in diabetes mellitus similar to L. Marzban et al.
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P.G. McTernan et al.
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L.L. Nielsen et al.
As with humans, diabe-
The glucagon-like peptides: a Pharmacology of exenatide (syn- tes has become a grow-
double-edged therapeutic sword? thetic exendin-4): a potential thera- ing problem with dogs
and cats in recent years

Trends Pharmacol. Sci. 24, 377-383 peutic for improved glycemic control due to their increasing
of type 2 diabetes.
life expectancy in com-
B. Thorens
Regul. Peptides 117, 77-88 (2004) bination with obesity
Gluco-incretin hormones in insulin A. Nourparvar et al.
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T.P. Vahl and D.A. D‘Alessio
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Despite the steady
Emerging drug candidates of dipep- Liraglutide: once-daily GLP-1 progress in research,
tidyl peptidase IV (DPP IV) inhibitor agonist for the treatment of type 2 the dramatic spread of
diabetes mellitus which

class for the treatment of type 2 is observed throughout
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F.K. Knop et al.
P. Westermark et al.
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Incretin-based therapy of type 2 Islet amyloid polypeptide, islet amy- the 21st century. Today,
diabetes mellitus.
loid, and diabetes mellitus.
diabetes mellitus is one
Curr. Protein Pept. Sci. 10, 46-55 Physiol. Rev. 91, 795-826 (2011) of the main causes of
death in most devel-

Peptides and Diabetes PEPTIDES
Bachem offers peptidic active pharmaceutical ingredients (generic APIs) and Clinalfa® basic ready-to-use formulations, sterile products for approved clinical studies, please see page18 or go to www.bachem.com Amylin (human)
Acetyl-Amylin (8-37) (human)
(Amlintide; IAPP (human)) Amylin (8-37) (mouse, rat)
Amylin (mouse, rat)
Acetyl-Amylin (8-37) (mouse, rat)
Amylin (1-13) (human)
Amylin (20-29) (human)
Amylin (8-37) (human)
C-Peptide 2 (rat)
C-PEPTIDE
Proinsulin C-Peptide (31-63)
Proinsulin C-Peptide (55-89)
(human)

([D ]Val7·10)-C-Peptide (human)
EAEDLQ[D ]VGQ[D ]VELGGGPGAGSLQPLA- Tyr-Proinsulin C-Peptide (55-89)
C-Peptide 1 (rat)
Peptides and Diabetes Exenatide
Gastric Inhibitory Polypeptide
Gastric Inhibitory Polypeptide (1-30)
INHIBITORY
POLYPEPTIDE
Gastric Inhibitory Polypeptide (3-42)
Gastric Inhibitory Polypeptide
Gastric Inhibitory Polypeptide (6-30)
amide (human)
H-6102
FISDYSIAMDKIHQQDFVNWLLAQK-NH2
Glucagon (1-29) (human, rat, porcine)
(Des-His1,Glu9)-Glucagon (1-29) amide
GLUCAGON
(human, rat, porcine)
AND OXYNTO-
([13C ]Leu14)-Glucagon (1-29) (human,
(Des-Thr5)-Glucagon (1-29)
(Des-Thr7)-Glucagon (1-29)
Biotinyl-Glucagon (1-29)
(human, rat, porcine)
(Met(O)27)-Glucagon (1-29)
Oxyntomodulin (bovine, dog, porcine)
GLUCAGON
(human, rat, porcine)
(Glucagon-37 (bovine, dog, porcine)) AND OXYNTO-
Glucagon (19-29)
Oxyntomodulin (human, mouse, rat)
(human, rat, porcine)
(Glucagon-37 (human, mouse, rat)) GRPP (human)
H-6062

Oxyntomodulin (30-37)
(bovine, dog, porcine)
GLP-1 (1-36) amide (human, bovine,
GLP-1 (7-36)-Lys(6-FAM) amide (hu-
GLUCAGON-LIKE guinea pig, mouse, rat)
man, bovine, guinea pig, mouse, rat)
GLP-1 (1-37) (human, bovine,
GLP-1 (7-37) (human, bovine, guinea
guinea pig, mouse, rat)
pig, mouse, rat) (Acetate salt)
GRG (Acetate salt) GLP-1 (7-36) amide
GLP-1 (7-37) (human, bovine, guinea
(chicken, common turkey)
pig, mouse, rat)
(Trifl uoroacetate salt)
GRG (Trifl uoroacetate salt) GLP-1 (7-36) amide (human, bovine,
guinea pig, mouse, rat)

Liraglutide
(Ser8)-GLP-1 (7-36) amide (human,
bovine, guinea pig, mouse, rat)
H-4592

GLP-1 (9-36) amide (human, bovine,
guinea pig, mouse, porcine, rat)
GLP-1 (7-36)-Lys(biotinyl) amide (hu-
man, bovine, guinea pig, mouse, rat)
H-5956
HAEGTFTSDVSSYLEGQAAKEFIAWLVKG
RK(biotinyl)-NH2
Peptides and Diabetes GLP-2 (1-33) (human)
GLP-2 (rat)
GLP-2 (1-34) (human)
H-4766

H-Asn-Pro-Glu-Tyr(PO H )-OH
rec IGF-II (1-67) (human)
INSULIN,
rec IGF-I (human)
FACTOR (IGF) IGF-I Analog
CYAAPLKPAKSC (Disulfi de bond) Lys-Lys-IRS-1 (891-902)
(dephosphorylated) (human)

IGF-I (1-3)
Insulin B (22-25)
IGF-I (24-41)
Pancreastatin (33-48) (human)
Pancreastatin (33-49) (porcine)
Pseudin-2
(Pyr1)-Apelin-13 (human, bovine,
mouse, rat)
Calcitonin (8-32) (salmon I)
(Disulfi de bonds, air oxidized) Peptides and Diabetes Exendin (9-39) Acetate
Glucagon
GENERIC APIs
GLP-1 (7-36) amide Acetate
IGF-I (1-3)
*offered on request ** offered under Bolar Exemption: This product is offered and sold in small quantities only and solely for uses reasonably related to privi- leged trials and studies for obtaining marketing Liraglutide Acetate**
authorization required by law (Bolar Exemption). GLP-1 (7-37) Acetate*
Bachem cannot be made liable for any infringe- ment of intellectual property rights. It is the sole and only responsibility of the purchaser or user of this product to comply with the relevant national rules and regulations.
(Pyr1)-Apelin-13 Acetate
GIP Acetate
1 mg/vial (Clinalfa basic)
500 μg/vial (Clinalfa basic)
Exendin (9-39) Acetate
10 mg/vial (Clinalfa basic)

GLP-1 (7-36) amide Acetate
100 μg/vial (Clinalfa basic)
PANCREATIC
ISLET OF
LANGERHANS

Islets of Langerhans.
Light micrograph of a section through
an islet of Langerhans (pale, centre) in
pancreas tissue. This clump of secre-
tory cells forms part of the endocrine
system of the body, which releases
hormones into the blood. It is com-
posed of numerous beta cells (purple),
which secrete insulin, and the less
numerous alpha cells (pink), which
secrete glucagon. Insulin stimulates
the uptake of glucose and amino
acids from the bloodstream, whereas
glucagon has the opposite effect; it
stimulates the breakdown of glycogen
in the tissues. This causes glucose
and amino acids to be released into
the blood.
KEYSTONE/SCIENCE PHOTO LIBRARY/CNRI Marketing & Sales Contact
Europe, Africa, Middle East and Asia Pacifi c: Bachem AG
Tel. +41 61 935 2323 Bachem Americas, Inc.
Tel. +1 888 422 2436
sales.us@bachem.com
Visit our website
www.bachem. com
or shop online
shop.bachem.com
All information is compiled to the best of our knowledge. We cannot be made liable for any possible errors or misprints. Some products may be restricted in certain countries.
www.bachem. com

Source: http://www.chayon.co.kr/email/2014/0321_peptide/Diabetes_Peptides.pdf

Acknowledgements

Basic Facts About 12th edition 2004 © British Columbia Schizophrenia Society "We'd like to change your mind" A LETTER TO YOUNG PEOPLE, EDUCATORS, PARENTS, AND OTHERS If you want to learn some basic facts about schizophrenia, we hope you will find this booklet useful. Please remember, the text is meant only as an introduction  it should not be used as a diagnostic tool.

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