The transcribed area of the 5' untranslated region of the mRNA contains one of the two intervening sequences in the human insulin gene, while the other one replaces the C-peptide coding region [1]. Type 2 diabetes is frequently treated using human insulin [2].

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Mothers with diabetes using insulin may nurse their infants. Exogenous insulin is excreted into breastmilk, including newer biosynthetic insulins (e.g., aspart, deglutec, detemir, glargine glulisine, lispro). Even direct administration of recombinant insulin orally to preterm infants is safe. Insulin is a normal component of breastmilk and may decrease the risk of type 1 diabetes in breastfed infants. Women taking insulin for type 2 diabetes have higher milk insulin levels than those controlled with diet alone.
Insulin requirements are reduced postpartum in women with type 1 diabetes, although postpartum insulin requirements do not significantly differ between breastfeeding and non-breastfeeding women. In general, insulin requirements are 30% to 50% lower than prepregnancy dosages immediately postpartum. Then the insulin requirements during breastfeeding average 21% lower than prepregnancy dosages, but there is wide variation. In one study, insulin requirements were lower than prepregnancy dosage only during the first week postpartum: 54% of prepregnancy dosage on day 2 and 73% on day 3 postpartum. On day 7 postpartum, insulin dosage returned to prepregnancy requirements. Another study found that dosage requirements did not return to normal for up to 6 weeks in some mothers. A third study found that at 4 months postpartum, patients with type 1 diabetes who exclusively breastfed had an average of 13% lower (range -52% to +40%) insulin requirement than their prepregnancy requirement. A retrospective case-control study found a 34% decrease in postpartum insulin requirement compare to preconception values. There was a nonsignificant trend towards lower requirements in exclusively breastfeeding mothers compared to partial or full formula feeding. A small study found that mothers on insulin pumps were found to have an average basal insulin rates 14% lower and carbohydrate-to-insulin ratios were 10% higher than pre-pregnancy settings. Breastfeeding appears to improve glucose postpartum glucose tolerance in mothers with gestational diabetes mellitus and in normal women.
A small, well-controlled study of women with type 1 diabetes mellitus using continuous subcutaneous insulin found that the average basal insulin requirement in women with type 1 diabetes who breastfed was 0.21 units/kg daily and the total insulin requirement was 0.56 units/kg daily. In similar women who did not breastfeed, the basal insulin requirement was 0.33 units/kg daily and the total insulin requirement was 0.75 units/kg daily. The 36% lower basal insulin requirement was thought to be caused by glucose use for milk production.
Lactation onset occurs later in patients with type 1 diabetes than in women without diabetes, with a greater delay in mothers with poor glucose control. Mothers with type 1 diabetes also discontinue nursing at a higher rate during the first week postpartum. Women with any form of diabetes during pregnancy had more problems with low milk supply than women without diabetes. Once established, lactation persists as long in mothers with diabetes as in mothers without diabetes. However, as in women without diabetes, smoking has a strong negative impact on lactation among mothers with type 1 diabetes. Other factors that have been identified as causes of shorter duration of breastfeeding among type 1 diabetic patients are more frequent caesarean sections and earlier delivery. Among patients with gestational diabetes, those treated with insulin have a delayed onset of lactogenesis II compared to those not treated with insulin.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date. Insulin in breastmilk is thought to be necessary for intestinal maturation of the infant and may help decrease the risk of contracting type 1 diabetes in breastfed infants.
◉ Effects on Lactation and Breastmilk
Proper insulin levels are necessary for lactation. Good glycemic control enhances maternal serum and milk prolactin concentrations and decreases the delay in the establishment of lactation that can occur in mothers with type 1 diabetes.
One-hundred two of 107 consecutive mothers with type 1 diabetes mellitus who delivered were followed at a Danish hospital. Mothers were given prenatal information on breastfeeding and were offered postnatal counseling by a nurse on the benefits of breastfeeding. All infants were admitted to the neonatal intensive care unit at about 2 hours of age for the following 24 hours. When possible, mothers either breastfed or pumped milk for their infants during this time. Mothers were contacted at 5 days and 4 months postpartum to determine their breastfeeding status. The rates of initiation of exclusive and nonexclusive breastfeeding and exclusive formula feeding and the rates at 4 months postpartum were no different from those of the Danish population.
Eight hundred eighty-three women with gestational diabetes were interviewed at 6 to 9 weeks postpartum. Those who had been treated with insulin more frequently reported having a delayed onset of lactogenesis II (>72 hours) postpartum than those not treated with insulin, independent of other maternal risk factors. The odds ratio of having delayed lactogenesis II was 3.1 among insulin-treated mothers compared to mothers with gestational diabetes who did not receive insulin.

[1]. Bell GI, et al. Sequence of the human insulin gene. Nature. 1980 Mar 6;284(5751):26-32.
[2]. Tseng CH, et al. Prolonged use of human insulin increases breast cancer risk in Taiwanese women with type 2 diabetes. BMC Cancer. 2015 Nov 4;15:846.

Insulin (human) is an insulin that is produced in the pancreas and involved in regulating the metabolism of carbohydrates (particularly glucose) and fats. Commonly thought of as a protein, it consists of two peptide chains, one containing 21 amino acid residues and the other containing 30; the chains are joined together by 2 disulfide bonds. Recombinant insulin is identical to human insulin, but is synthesised by inserting the human insulin gene into E. coli, which then produces insulin for human use. It is used in the treatment of type I and type II diabetes. It has a role as a hypoglycemic agent.
See also: Insulin Human (annotation moved to).

C257H383N65O77S6

5807.58

5805.644

11061-68-0

118984375

White to off-white solid powder

-13.1

78

89

179

405

14600

52

[H]/N=C(/NCCC[C@@H](C(NCC(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N1[C@H](C(N[C@H](C(N[C@H](C(=O)O)[C@@H](O)C)=O)CCCCN)=O)CCC1)=O)[C@@H](O)C)=O)CC1=CC=C(O)C=C1)=O)CC1=CC=CC=C1)=O)CC1=CC=CC=C1)=O)=O)NC([C@@H](NC(CNC([C@H]1NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2N=CNC=2)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@H](C(=O)N)NC([C@H](C(C)C)NC([C@H](CC2=CC=CC=C2)N)=O)=O)=O)CCC(=O)N)=O)CC2N=CNC=2)=O)CC(C)C)=O)CSSC[C@@H]2C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](CSSC[C@@H](C(N2)=O)NC([C@@H](NC([C@@H](NC([C@H](C(C)C)NC([C@H]([C@@H](CC)C)NC(CN)=O)=O)=O)CCC(=O)O)=O)CCC(=O)N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@H](C(N[C@H](C(=O)O)CC(=O)N)=O)CSSC1)=O)[C@@H](CC)C)=O)CO)=O)[C@@H](O)C)=O)=O)=O)CCC(=O)O)=O)\N

PBGKTOXHQIOBKM-FHFVDXKLSA-N

InChI=1S/C257H383N65O77S6/c1-29-131(23)205(313-193(339)104-259)252(393)317-204(130(21)22)248(389)288-159(75-82-200(349)350)217(358)282-156(71-78-189(263)335)221(362)308-183-116-403-404-117-184-243(384)305-178(111-324)240(381)294-162(88-123(7)8)225(366)295-168(95-140-53-61-146(329)62-54-140)228(369)283-154(69-76-187(261)333)218(359)290-161(87-122(5)6)223(364)285-158(74-81-199(347)348)220(361)302-174(101-190(264)336)235(376)298-170(97-142-57-65-148(331)66-58-142)231(372)309-182(242(383)304-176(255(396)397)103-192(266)338)115-402-401-114-181(214(355)273-107-194(340)278-153(72-79-197(343)344)216(357)281-151(51-42-84-271-257(267)268)212(353)272-108-195(341)279-166(93-138-46-36-32-37-47-138)227(368)297-167(94-139-48-38-33-39-49-139)230(371)299-171(98-143-59-67-149(332)68-60-143)238(379)320-208(135(27)327)254(395)322-85-43-52-186(322)246(387)286-152(50-40-41-83-258)222(363)321-209(136(28)328)256(398)399)311-250(391)203(129(19)20)316-236(377)164(90-125(11)12)292-229(370)169(96-141-55-63-147(330)64-56-141)296-224(365)160(86-121(3)4)289-210(351)133(25)277-215(356)157(73-80-198(345)346)287-247(388)202(128(17)18)315-237(378)165(91-126(13)14)293-233(374)173(100-145-106-270-120-276-145)301-239(380)177(110-323)280-196(342)109-274-213(354)180(113-400-405-118-185(310-244(183)385)245(386)319-207(134(26)326)253(394)306-179(112-325)241(382)318-206(132(24)30-2)251(392)312-184)307-226(367)163(89-124(9)10)291-232(373)172(99-144-105-269-119-275-144)300-219(360)155(70-77-188(262)334)284-234(375)175(102-191(265)337)303-249(390)201(127(15)16)314-211(352)150(260)92-137-44-34-31-35-45-137/h31-39,44-49,53-68,105-106,119-136,150-186,201-209,323-332H,29-30,40-43,50-52,69-104,107-118,258-260H2,1-28H3,(H2,261,333)(H2,262,334)(H2,263,335)(H2,264,336)(H2,265,337)(H2,266,338)(H,269,275)(H,270,276)(H,272,353)(H,273,355)(H,274,354)(H,277,356)(H,278,340)(H,279,341)(H,280,342)(H,281,357)(H,282,358)(H,283,369)(H,284,375)(H,285,364)(H,286,387)(H,287,388)(H,288,389)(H,289,351)(H,290,359)(H,291,373)(H,292,370)(H,293,374)(H,294,381)(H,295,366)(H,296,365)(H,297,368)(H,298,376)(H,299,371)(H,300,360)(H,301,380)(H,302,361)(H,303,390)(H,304,383)(H,305,384)(H,306,394)(H,307,367)(H,308,362)(H,309,372)(H,310,385)(H,311,391)(H,312,392)(H,313,339)(H,314,352)(H,315,378)(H,316,377)(H,317,393)(H,318,382)(H,319,386)(H,320,379)(H,321,363)(H,343,344)(H,345,346)(H,347,348)(H,349,350)(H,396,397)(H,398,399)(H4,267,268,271)/t131-,132-,133-,134+,135+,136+,150-,151-,152-,153-,154-,155-,156-,157-,158-,159-,160-,161-,162-,163-,164-,165-,166-,167-,168-,169-,170-,171-,172-,173-,174-,175-,176-,177-,178-,179-,180-,181-,182-,183-,184-,185-,186-,201-,202-,203-,204-,205-,206-,207-,208-,209-/m0/s1

(4S)-4-[[2-[[(1R,6R,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,50S,53S,56S,59S,62S,65S,68S,71S,74R,77S,80S,83S,88R)-88-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[(2-aminoacetyl)amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]-6-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-47-[[(1S)-3-amino-1-carboxy-3-oxopropyl]carbamoyl]-53-(2-amino-2-oxoethyl)-62-(3-amino-3-oxopropyl)-77-[(2S)-butan-2-yl]-24,56-bis(2-carboxyethyl)-83-[(1R)-1-hydroxyethyl]-12,71,80-tris(hydroxymethyl)-33,50,65-tris[(4-hydroxyphenyl)methyl]-15-(1H-imidazol-4-ylmethyl)-27-methyl-18,30,36,59,68-pentakis(2-methylpropyl)-7,10,13,16,19,22,25,28,31,34,37,40,49,52,55,58,61,64,67,70,73,76,79,82,85,87-hexacosaoxo-21,39-di(propan-2-yl)-3,4,44,45,90,91-hexathia-8,11,14,17,20,23,26,29,32,35,38,41,48,51,54,57,60,63,66,69,72,75,78,81,84,86-hexacosazabicyclo[72.11.7]dononacontane-42-carbonyl]amino]acetyl]amino]-5-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[(2S)-2-[[(2S)-6-amino-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxohexan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-oxopentanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~10 mg/mL (~1.72 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)