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]

Fasting and non-fasted hyperglycemia are dose-dependently attenuated by oral calcitonin salmon treatment during the intervention period. Oral Calcitonin salmon treatment by dose reduces HbA1c levels by 1.7% and diabetic hyperglycemia by approximately 9 mM at the end of the study period. Moreover, oral Calcitonin salmon treatment results in a dose-dependently significant decrease in glucose excursions during the oral glucose tolerance test. Furthermore, oral Calcitonin Salmon treatment attenuates hyperglucagonaemia and hypersecretion of total glucagon-like peptide-1, primarily in the basal state, while maintaining hyperinsulinemia. Finally, at the conclusion of the study, pancreatic beta-cell function and beta-cell area are improved dose-dependently by oral Calcitonin salmon treatment[1].

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- Attenuation of Hyperglycemia in Zucker Diabetic Fatty (ZDF) Rats:
1. Fasting blood glucose (FBG) reduction: Male ZDF rats (8-week-old) were orally administered Calcitonin salmon at doses of 1, 5, and 25 μg/kg once daily for 8 weeks. The 25 μg/kg group showed the most significant effect: FBG decreased from ~28 mmol/L (week 0) to ~18 mmol/L (week 8), a reduction of ~35% vs. solvent control group (~30 mmol/L at week 8). [1]
2. Glycated hemoglobin (HbA1c) improvement: 25 μg/kg Calcitonin salmon reduced HbA1c levels by ~25% (from ~8.5% to ~6.4%) vs. control after 8 weeks, indicating long-term glycemic control. [1]
- Preservation of Pancreatic β-Cell Area and Function:
1. β-cell area protection: Immunohistochemical staining of pancreatic sections showed Calcitonin salmon (25 μg/kg) increased β-cell area from ~8% (control) to ~11.2% (a ~40% increase) by reducing β-cell apoptosis (TUNEL assay: apoptotic β cells decreased by ~55% vs. control). [1]
2. Insulin secretion enhancement: Glucose tolerance test (GTT) revealed 25 μg/kg Calcitonin salmon increased serum insulin levels by ~30% at 30 minutes post-glucose load vs. control; pancreatic insulin content was ~2.2-fold higher than control, indicating improved β-cell secretory function. [1]
- Improvement of Insulin Sensitivity:
Calcitonin salmon (15, 25 μg/kg) increased insulin-mediated glucose uptake in adipose tissue and skeletal muscle by ~20%–30% (measured via 2-deoxyglucose uptake assay), suggesting enhanced peripheral insulin sensitivity. [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: Salmon calcitonin (1, 5, 25 μg/kg, 8 weeks) had no significant effect on the body weight of ZDF rats; the final body weight of the 25 μg/kg group (approximately 380 g) was comparable to that of the diabetic control group (approximately 375 g). [1]
2. Liver and kidney function: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Cr) levels in the salmon calcitonin group were within the normal range and showed no significant difference from those in the diabetic control group. [1]
3. Histopathology: No abnormal lesions were observed in the liver, kidney, pancreas, or gastrointestinal tract of the salmon calcitonin-treated rats by 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 and chemical category: Salmon calcitonin is a polypeptide hormone composed of 32 amino acids, naturally extracted from the terminal gill glands of salmon. It belongs to the calcitonin family and has higher biological activity and a longer plasma half-life compared with human calcitonin. [1] - Mechanism of action against diabetes: 1. Protection of pancreatic β cells: Salmon calcitonin binds to the calcitonin receptor (CTR) on β cells, activates intracellular signaling pathways (such as the cAMP/PKA pathway), thereby reducing β cell apoptosis, promoting β cell proliferation, and maintaining the number of β cells. [1] 2. Regulation of glucose metabolism: It enhances insulin secretion from β cells in a glucose-dependent manner and improves peripheral insulin sensitivity (uptake of glucose by fat/muscle), thereby lowering blood glucose. [1]
- Dosage Form Characteristics: This study used an oral formulation of salmon calcitonin, overcoming the limitations of traditional calcitonin (currently only available in injectable form due to low oral bioavailability), and providing a more convenient route of administration for patients with chronic diseases such as 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

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

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (0.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (0.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (0.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 50 mg/mL (14.57 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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