Gene, mRNA, and precursor Regulation of synthesis Receptors Agonists and Antagonists Biological functions Clinical implications
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INSULIN

Gene, mRNA, and precursor Regulation of synthesis Receptors Agonists and Antagonists Biological functions Clinical implications
Product Name
INSULIN
CAS No.
11061-68-0
Chemical Name
INSULIN
Synonyms
INSULIN, RECOMBINANT HUMAN;INSULIN HUMAN;rh-Insulin;Insulin (human) CRS;D03230;Umulin;INSULIN;novolin;Humulin;humuline
CBNumber
CB7336087
Molecular Formula
C257H383N65O77S6
Formula Weight
0
MOL File
Mol file
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INSULIN Property

Melting point:
>200°C (dec.)
storage temp. 
-20°C
solubility 
acidified water, pH 2.0: 2 mg/mL
form 
solution
color 
White
Water Solubility 
Soluble up to 10mg/ml in pH <3 or in the presence of surfactants. Adjusting pH with a volatile acid (such as formic acid) prior to dry down will allow the product to be re-dissolved in water.
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Safety

Safety Statements 
22-24/25
WGK Germany 
3
RTECS 
NM8900250
3-10
HS Code 
2937120000
Toxicity
LD50 intraperitoneal in mouse: 3937units/kg
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
I1507
Product name
Insulin human
Purity
≥95% (HPLC), semisynthetic, powder
Packaging
0.1mg
Price
$780
Updated
2024/03/01
Sigma-Aldrich
Product number
I1507
Product name
Insulin human
Purity
≥95% (HPLC), semisynthetic, powder
Packaging
0.5mg
Price
$1112
Updated
2024/03/01
Sigma-Aldrich
Product number
407709
Product name
Insulin, Zinc, Human, Recombinant,
Packaging
50mg
Price
$242
Updated
2024/03/01
Sigma-Aldrich
Product number
1342106
Product name
Insulin human
Purity
United States Pharmacopeia (USP) Reference Standard
Packaging
100mg
Price
$510
Updated
2024/03/01
Sigma-Aldrich
Product number
11376497001
Product name
Insulin, human
Purity
recombinant (yeast)
Packaging
100mg
Price
$226
Updated
2024/03/01
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INSULIN Chemical Properties,Usage,Production

Gene, mRNA, and precursor

The human preproINS gene, INS, is located at 11p15.5 and consists of three exons. In mice, it is located on chromosome 7. There are many regulatory elements, such as A-box, GG box, and the cAMP response element, in the promoter region. The coding region of human and tilapia preproINS mRNAs comprises 330 and 339 bases, respectively. In humans, INS forms a gene cluster with IGF2 and H19, which is a gene for a long noncoding RNA.

Regulation of synthesis

INS gene transcription is stimulated by glucose in mammals, and glucose treatment results in a 2- to 5-fold elevation within 60–90min. Long-term exposure to physiological concentrations of estradiol-17β increases the β-cell content, INS gene expression, and INS release in mice. Fasting reduces the expression levels of two INS genes in the trout.

Receptors

INS receptors (INSRs) are heterotetrameric glycoproteins containing many phosphorylated or glycosylated sites. INS binds to the two extracellular α-subunits linked by a disulfide bond. The two β-subunits are connected to the α-subunits by a disulfide bond and contain a tyrosine kinase domain in their intracellular region. Human INSR is encoded by a single gene, INSR, location 19p13.3-p13.2, comprising 22 exons.INSRencodes 1382 aa residues of the ISNR precursor, which contains a signal peptide and α- and β-subunits. Human INSR generates two alternative splicing variants (INSR-A and -B) that differ at the carboxyl terminus of their α-subunit. INSR-A lacks the terminus encoded by exon 11. INSR-B has not been detected in the chicken or Xenopus.  There are three types of hybrid receptors among these INSRs and the IGF-I receptor (IGF-IR), and their expression ratio influences the INS action at the target organs. Dysregulation of the INSR-A/INSR-B ratio is associated with INS resistance, aging, and increased proliferative activity of normal and neoplastic tissues. The dissociation constants (Kd) of human INS to human INSR and IGF-1R are 0.23 and 16nM, respectively. IGF-I binds to hybrid receptors with at least a 50-fold higher affinity than INS, irrespective of the splicing variant. Guinea pig INSR shows an exceptionally higher affinity (Kd= 0.083nM). Several fish species have multiple INSR genes that show different expression patterns among tissues. Human INS binds to fish INSR at a Kd of 0.67 and 0.15nM in the trout and carp, respectively.

Agonists and Antagonists

IGFs bind to INSR, but INS binds to IGF-IR with low affinity. Several synthetic peptides (S519 and RB539) show agonistic effects with a high affinity to INSR. Fish INSs bind mammalian INSR with high affinity and vice versa. RB537, S661, and S961 are INSR antagonists with high affinity. S961 shows an agonistic effect only on 3H-thymidine incorporation

Biological functions

INS is a key regulator of glucose homeostasis in mammals because the peptide is the only hormone that lowers blood glucose levels.  INSR-A mainly enhances the effects of IGF-II during embryogenesis and fetal development, whereas INSR-B is predominantly expressed in adults and enhances the metabolic effects of INS. ProINS binds to INSR-A, which is present in the nervous system, to elicit antiapoptotic and neuroprotective effects in the developing and postnatal nervous system. In the pancreas, the exocrine and endocrine components stimulate each other via intrapancreatic axes of communication. The insular-acinar axis is involved in the regulation of pancreatic digestive enzyme production in acinar cells located in the blood downstream of β-cells, and the acini-insular axis is involved in the regulation of INS release by pancreatic enzymes.

Clinical implications

Diabetes is classified as type 1 or type 2. Type 1 diabetes (INS-dependent diabetes mellitus) results from the autoimmune destruction of β-cells. Type 2 diabetes (noninsulin-dependent diabetes mellitus) is a metabolic disorder characterized by hyperglycemia due to an absolute or relative lack of INS or cellular resistance to INS. In mammals and fish, the administration of alloxan or streptozotocin selectively destroys β-cells, producing a type 2 diabetes model.

Description

Insulin (INS) is the only hormone lowering blood glucose levels in vertebrates. However, the importance of insulin in the carbohydrate metabolism may differ between mammals and other vertebrates. Frederick Banting and Charles Best discovered a substance that lowered blood sugar levels in the dog pancreas in 1921, and this was immediately applied to diabetes care. The primary structure of INS has been reported in many vertebrates, including agnathans, fish, and tetrapods.

Chemical Properties

White or almost white powder.

Uses

Insulin shows a broad range of activities on a variety of somatic cells. Recombinant human insulin can be used to stimulate growth and proliferation of cultured cells and to investigate insulin activity on sensitive cells used in research studies. It is also a component of serum-free media formulations for most primary cells and cell lines.

Uses

Antidiabetic.

brand name

Humulin (Lilly); Novolin (Novo Nordisk); Velosulin (Novo Nordisk).

General Description

The INS gene encodes for preproinsulin, which is enzymatically converted into insulin. Insulin is produced in the insulin-producing pancreatic β cells. Preproinsulin is converted to proinsulin in ER and proinsulin is then proteolytically processed to form insulin in newly-forming insulin secretory granules. Insulin production is tightly regulated by specific DNA elements present within ~400 bp in the proximal region of the INS promoter.

Biochem/physiol Actions

Insulin is responsible for two types of actions- excitatory and inhibitory. In its excitatory role, it increases the uptake of glucose and lipid synthesis, and in its inhibitory role it inhibits glycogenolysis, gluconeogenesis, lipolysis, proteolysis and ketogenesis. Aberrant insulin secretion leads to various disorders such as diabetes, hyperglycemia or hypoglycaemia. Type I diabetes is a result of autoimmune destruction of β cells of pancreas, which leads to depletion of insulin. Mutant INS-gene Induced Diabetes of Youth (MIDY) syndrome is an autosomal dominant disorder caused by missense mutations, which lead to aberrant proinsulin folding. Impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) is caused by resistance to insulin-stimulated glucose uptake.

Clinical Use

In mammals and chickens, INS levels are routinely measured using commercial kits, and several studies have established specific immunoassays for fish. Many INS analogs, which show different durations of action, have been developed to treat diabetes. Alternative INS administration methods other than injection are via the lungs, nose, skin, and mouth. These have been developed using the insulin encapsulation technique with micro- or nanodelivery systems. Many medical drugs that stimulate INS release, both directly and indirectly, are commercially available. Sulfonylurea and glinides stimulate β-cells directly. The incretin GLP-1 analog can lower glucose concentrations by augmenting insulin secretion and suppressing glucagon release. In addition the dipeptidyl peptidase-4 (DPP-4) inhibitor inhibits incretin degradation and indirectly enhances the stimulation of incretin to β-cells. Thiazolidinedione improves the action of INS in the muscle and adipose tissue. Cone snail (Conus geographus) G1 is a naturally occurring B-chainminimized mimetic of INS, which strongly binds to human and fish INSR and activates receptor signaling. This peptide induces extremely rapid hypoglycemic shock.

in vitro

methotrexate (mtx) was found to be linked to insulin covalently. as effectively as insulin, insulin-mtx complex competed with 125i-insulin for insulin receptor. it was found that ic50 and ki for insulin-mtx were 93.82 nm and 91.88 nm, respectively, whereas those for insulin were 5.01 nm and 4.85 nm, respectively [1].

in vivo

previous study showed that insulin-stimulated glucose uptake in extensor muscles from sjl mice was reduced, but the basal uptake rates were not different. in another mouse study, knockdown of tc10α but not tc10β in 3t3-l1 adipocytes resulted in a inhibition of both insulin-stimulated glucose uptake and glut4 translocation [2].

IC 50

5.01 nmol/l for insulin receptor

storage

Store at -20°C

Structure and conformation

Human preproINS consists of 110 aa residues: 24 in the signal peptide, 30 in the B-chain, 31 in the C-peptide, and 21 in the A-chain. The signal peptide and C-peptide are excised from the preproINS to produce the mature peptide, consisting of heterodimeric A- and B-chains. Six cysteine residues are conserved throughout evolution from agnathans to mammals. Furthermore, the N-terminal seven aa residues of the A-chain and the receptor binding region of the B-chain (Gly-Phe-Phe-Tyr) are highly conserved. Mr 5808, pI 5.3. INS is soluble under acidic and alkaline conditions and almost insoluble at neutral pH. INS can be stored for up to 6 months at 4°C in 1M acetic acid. Long-term storage at an alkaline pH increases the rate of deamidation and aggregation. One IU is equivalent to 0.0347mg human INS.

References

[1] ou x,kuang a,liang z,peng x,zhong y. the binding characteristics of insulin-mtx to insulin receptor. hua xi yi ke da xue xue bao.2001 dec;32(4):538-40.
[2] leney se,tavaré jm. the molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets. j endocrinol.2009 oct;203(1):1-18.

INSULIN Preparation Products And Raw materials

Raw materials

Preparation Products

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INSULIN Suppliers

Shanghai Universal Biotech Co.,Ltd
Tel
13774214275
Email
gaojun@univ-bio.com
Country
China
ProdList
24990
Advantage
58
3B Pharmachem (Wuhan) International Co.,Ltd.
Tel
821-50328103-801 18930552037
Fax
86-21-50328109
Email
3bsc@sina.com
Country
China
ProdList
15839
Advantage
69
Adamas Reagent, Ltd.
Tel
400-6009262 16621234537
Fax
021-64823266
Email
chenyj@titansci.com
Country
China
ProdList
14103
Advantage
59
Hunan Hui Bai Shi Biotechnology Co., Ltd.
Tel
0731-85526065 13308475853
Email
ivy@hnhbsj.com
Country
China
ProdList
4552
Advantage
62
Spectrum Chemical Manufacturing Corp.
Tel
021-021-021-67601398-809-809-809 15221380277
Fax
021-57711696
Email
marketing_china@spectrumchemical.com
Country
China
ProdList
9658
Advantage
60
Wuhan Fortuna Chemical Co., Ltd
Tel
027-59207852 13308628970
Fax
QQ3130921841
Email
buy@fortunachem.com
Country
China
ProdList
2876
Advantage
58
Dalian Meilun Biotech Co., Ltd.
Tel
0411-62910999 13889544652
Email
meilunui@163.com
Country
China
ProdList
4727
Advantage
58
ShangHai YuanYe Biotechnology Co., Ltd.
Tel
021-61312847 13636370518
Fax
021-55068248
Email
shyysw007@163.com
Country
China
ProdList
4940
Advantage
60
Beijing HuaMeiHuLiBiological Chemical
Tel
010-56205725
Fax
010-65763397
Email
waley188@sohu.com
Country
China
ProdList
12335
Advantage
58
Shanghai Ruji Biology Technology Co., Ltd.
Tel
+86-21-65211385-8001 36031160
Fax
+86-21-65211385-8004
Email
sales@shruji.com
Country
China
ProdList
3224
Advantage
55
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View Lastest Price from INSULIN manufacturers

hebei hongtan Biotechnology Co., Ltd
Product
Insulin 11061-68-0
Price
US $50.00-30.00/box
Min. Order
1box
Purity
99.99%
Supply Ability
1000
Release date
2024-03-14
Binzhou Lista Trading Limited
Product
Insuline 11061-68-0
Price
US $150.00-135.00/box
Min. Order
1box
Purity
99.99%
Supply Ability
200boxes
Release date
2024-08-12
Shanghai Likang New Materials Co., Limited
Product
Insulin 11061-68-0
Price
US $30.00-28.00/box
Min. Order
100box
Purity
99%
Supply Ability
1kg
Release date
2024-05-28

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