Calcitonin salmon   中文名称: 鲑鱼降钙素

Amylin, Calcitonin receptor
- Calcitonin salmon targets calcitonin receptors (CTR) (expressed on pancreatic β cells and peripheral tissues) to regulate glucose metabolism and protect pancreatic β cells. [1]

口服降钙素鲑鱼治疗剂量依赖性地减轻干预期间的空腹和非空腹高血糖。在研究期结束时，口服鲑鱼降钙素治疗可将糖尿病高血糖降低约 9 mM，并将 HbA1c 水平降低 1.7%。此外，在口服葡萄糖耐量试验期间，口服降钙素鲑鱼治疗可观察到葡萄糖偏移的显着减少，这是剂量依赖性的。此外，口服降钙素鲑鱼治疗可维持高胰岛素血症并减轻高胰高血糖素血症和主要在基础状态下的总胰高血糖素样肽-1的过度分泌。最后，口服降钙素鲑鱼治疗在研究结束时可剂量依赖性地改善胰腺 β 细胞功能和 β 细胞面积[1]。

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- 改善Zucker糖尿病肥胖（ZDF）大鼠高血糖:
1. 空腹血糖（FBG）降低：8周龄雄性ZDF大鼠口服给予Calcitonin salmon（1、5、25 μg/kg），每日1次，持续8周。25 μg/kg组效果最显著：FBG从第0周的~28 mmol/L降至第8周的~18 mmol/L，较溶剂对照组（第8周~30 mmol/L）降低约35%。[1]
2. 糖化血红蛋白（HbA1c）改善：25 μg/kg Calcitonin salmon处理8周后，HbA1c较对照组降低约25%（从~8.5%降至~6.4%），提示长期血糖控制效果。[1]
- 保护胰岛β细胞面积与功能:
1. β细胞面积保护：胰腺切片免疫组化显示，25 μg/kg Calcitonin salmon使β细胞面积从对照组的~8%增至~11.2%（增加约40%），同时通过TUNEL实验证实β细胞凋亡率较对照组降低约55%。[1]
2. 胰岛素分泌增强：葡萄糖耐量试验（GTT）显示，25 μg/kg Calcitonin salmon组在葡萄糖负荷后30分钟，血清胰岛素水平较对照组升高约30%；胰腺胰岛素含量为对照组的~2.2倍，提示β细胞分泌功能改善。[1]
- 提高胰岛素敏感性:
Calcitonin salmon（15、25 μg/kg）使脂肪组织和骨骼肌中胰岛素介导的葡萄糖摄取增加约20%–30%（通过2-脱氧葡萄糖摄取实验检测），提示外周胰岛素敏感性增强。[1]

Rats: Oral Calcitonin salmon (sCT: 0.5, 1.0, or 2 mg/kg) or oral vehicle is administered twice daily to male ZDF rats from 8 to 18 weeks of age. The control group consists of Zucker lean rats. The levels of pancreatic and incretin hormones, glycosylated hemoglobin (HbA1c), and blood glucose measured both fasting and non-fasting. Beta-cell area and function were assessed, and the oral and intraperitoneal glucose tolerance tests were compared[1].

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- ZDF Rat Diabetic Model Experiment:
1. Animal preparation: Male Zucker diabetic fatty (ZDF) rats (8-week-old, initial weight 280–320 g) and lean Zucker rats (as normal control) were acclimated for 1 week (22°C, 12h light/dark cycle, free access to standard chow and water). [1]
2. Grouping: Rats were divided into 4 groups (n=8 per group):
- Normal control: Lean Zucker rats (no treatment); [1]
- Diabetic control: ZDF rats (oral gavage of solvent: 0.1% bovine serum albumin (BSA) in sterile saline); [1]
- Calcitonin salmon 1 μg/kg: ZDF rats (oral gavage of 1 μg/kg Calcitonin salmon in solvent); [1]
- Calcitonin salmon 5 μg/kg: ZDF rats (oral gavage of 5 μg/kg Calcitonin salmon in solvent); [1]
- Calcitonin salmon 25 μg/kg: ZDF rats (oral gavage of 25 μg/kg Calcitonin salmon in solvent). [1]
3. Drug preparation: Calcitonin salmon was dissolved in 0.1% BSA-saline to prepare the required concentrations, and freshly prepared before daily administration. [1]
4. Administration: Oral gavage once daily for 8 weeks; volume of administration was 1 mL/kg body weight. [1]
5. Sample collection & detection:
- Weekly measurements: FBG (tail vein blood, glucose meter) and body weight; [1]
- Week 8: GTT (2 g/kg glucose intraperitoneal injection, serum insulin measured via ELISA); HbA1c (whole blood, chromatographic assay); [1]
- Euthanasia: Rats were euthanized at week 8; pancreas was harvested (fixed in 4% paraformaldehyde for β-cell immunohistochemistry/TUNEL assay, or homogenized for insulin content measurement); adipose/muscle tissues were collected for insulin sensitivity assay. [1]

- In Vivo Safety:
1. Body weight: Calcitonin salmon (1, 5, 25 μg/kg, 8 weeks) had no significant effect on body weight of ZDF rats; final body weight of 25 μg/kg group (~380 g) was comparable to diabetic control (~375 g). [1]
2. Hepatic/renal function: Serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and creatinine (Cr) in Calcitonin salmon groups were within normal ranges, with no significant difference vs. diabetic control. [1]
3. Histopathology: No abnormal lesions were observed in liver, kidney, pancreas, or gastrointestinal tissues of Calcitonin salmon-treated rats via hematoxylin-eosin (HE) staining. [1]

[1]. Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats. Br J Pharmacol. 2012 Sep;167(1):151-63.

- Natural Source & Chemical Class: Calcitonin salmon is a 32-amino acid polypeptide hormone naturally isolated from the ultimobranchial glands of salmon. It belongs to the calcitonin family, with higher biological potency and longer plasma half-life than human calcitonin. [1]
- Mechanism of Antidiabetic Action:
1. Pancreatic β-cell protection: Calcitonin salmon binds to CTR on β cells, activating intracellular signaling pathways (e.g., cAMP/PKA) to reduce β-cell apoptosis, promote β-cell proliferation, and preserve β-cell mass. [1]
2. Glucose metabolism regulation: It enhances insulin secretion from β cells in a glucose-dependent manner and improves peripheral insulin sensitivity (adipose/muscle glucose uptake), thereby lowering blood glucose. [1]
- Dosage Form Feature: The study used an oral formulation of Calcitonin salmon, which addresses the traditional limitation of calcitonin (only available as injectable due to poor oral bioavailability) and provides a more convenient administration route for chronic diseases like diabetes. [1]

C145H240N44O48S2

3431.85

3429.713

C, 50.75; H, 7.05; N, 17.96; O, 22.38; S, 1.87

47931-85-1

16220016

White to off-white solid powder

1.5±0.1 g/cm3

1.677

-12.48

1558.81

52

55

99

239

7970

34

C(N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@H](O)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@H](O)C)C(N1CCC[C@H]1C(=O)N)=O)(=O)[C@@H](NC(=O)[C@H]([C@H](O)C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC([C@@H]1CSSC[C@@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@]([H])(C(N1)=O)[C@H](O)C)=O)CO)=O)CC(C)C)=O)CC(=O)N)=O)CO)=O)N)=O)CC1NC=NC=1)CC1C=CC(=CC=1)O

BBBFJLBPOGFECG-VJVYQDLKSA-N

InChI=1S/C145H240N44O48S2/c1-65(2)45-86(175-139(232)110(70(11)12)183-136(229)99-63-239-238-62-79(148)117(210)178-96(59-191)134(227)174-92(52-104(151)202)131(224)172-90(49-69(9)10)129(222)180-98(61-193)135(228)187-114(74(16)197)142(235)181-99)118(211)158-55-106(204)162-80(25-18-20-40-146)120(213)169-89(48-68(7)8)128(221)179-97(60-192)133(226)167-83(34-37-102(149)200)122(215)165-85(36-39-109(207)208)123(216)171-88(47-67(5)6)127(220)173-91(51-77-54-156-64-161-77)130(223)164-81(26-19-21-41-147)121(214)170-87(46-66(3)4)126(219)166-84(35-38-103(150)201)125(218)186-113(73(15)196)141(234)177-94(50-76-30-32-78(199)33-31-76)143(236)189-44-24-29-101(189)137(230)168-82(27-22-42-157-145(154)155)124(217)185-112(72(14)195)140(233)176-93(53-105(152)203)132(225)184-111(71(13)194)138(231)160-56-107(205)163-95(58-190)119(212)159-57-108(206)182-115(75(17)198)144(237)188-43-23-28-100(188)116(153)209/h30-33,54,64-75,79-101,110-115,190-199H,18-29,34-53,55-63,146-148H2,1-17H3,(H2,149,200)(H2,150,201)(H2,151,202)(H2,152,203)(H2,153,209)(H,156,161)(H,158,211)(H,159,212)(H,160,231)(H,162,204)(H,163,205)(H,164,223)(H,165,215)(H,166,219)(H,167,226)(H,168,230)(H,169,213)(H,170,214)(H,171,216)(H,172,224)(H,173,220)(H,174,227)(H,175,232)(H,176,233)(H,177,234)(H,178,210)(H,179,221)(H,180,222)(H,181,235)(H,182,206)(H,183,229)(H,184,225)(H,185,217)(H,186,218)(H,187,228)(H,207,208)(H4,154,155,157)/t71-,72-,73-,74-,75-,79+,80+,81+,82+,83+,84+,85+,86+,87+,88+,89+,90+,91+,92+,93+,94+,95+,96+,97+,98+,99+,100+,101+,110+,111+,112+,113+,114+,115+/m1/s1

(4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(4R,7S,10S,13S,16S,19S,22R)-22-amino-16-(2-amino-2-oxoethyl)-7-[(1R)-1-hydroxyethyl]-10,19-bis(hydroxymethyl)-13-(2-methylpropyl)-6,9,12,15,18,21-hexaoxo-1,2-dithia-5,8,11,14,17,20-hexazacyclotricosane-4-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S,3R)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S,3R)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[2-[[(2S)-1-[[2-[[(2S,3R)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid

Osteobion; Calcitonin; Astronin; Steocin; TZ-CT

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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

H2O: ~100 mg/mL (~29.1 mM)
DMSO: ~50 mg/mL (~14.6 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (0.73 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (0.73 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (0.73 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 50 mg/mL (14.57 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。