Insulin levels modulator
目录号 : GC31526Insulinlevelsmodulator可用于治疗糖尿病。
Cas No.:1019254-94-4
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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Insulin levels modulator could be used to treat diabetes.
[1]. WO 2008045484 A1.
Cas No. | 1019254-94-4 | SDF | |
Canonical SMILES | O=C(C1=C(CCC)N(C2=NC=C(C)C(C3=CC=CS3)=N2)N=C1)NCC4=CN=CN4C | ||
分子式 | C21H23N7OS | 分子量 | 421.52 |
溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。 为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。 |
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Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
制备储备液 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.3724 mL | 11.8618 mL | 23.7237 mL |
5 mM | 0.4745 mL | 2.3724 mL | 4.7447 mL |
10 mM | 0.2372 mL | 1.1862 mL | 2.3724 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方) | ||||||||||
% DMSO % % Tween 80 % saline | ||||||||||
计算重置 |
计算结果:
工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Role of Insulin in Health and Disease: An Update
Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.
Insulin as an immunomodulatory hormone
Insulin plays an indispensable role in the management of hyperglycaemia that arises in a variety of settings, including Type I and II diabetes, gestational diabetes, as well as is in hyperglycaemia following a severe inflammatory insult. However, insulin receptors are also expressed on a range of cells that are not canonically implicated in glucose homeostasis. This includes immune cells, where the anti-inflammatory effects of insulin have been repeatedly reported. However, recent findings have also implicated a more involved role for insulin in shaping the immune response during an infection. This includes the ability of insulin to modulate immune cell differentiation and polarisation as well as the modulation of effector functions such as biocidal ROS production. Finally, inflammatory mediators can through both direct and indirect mechanisms also regulate serum insulin levels, suggesting that insulin may be co-opted by the immune system during an infection to direct immunological operations. Collectively, these observations implicate insulin as a bona fide immune-modulating hormone and suggest that a better understanding of insulin's immunological function may aid in optimising insulin therapy in a range of clinical settings.
Benefits, mechanisms, and risks of intermittent fasting in metabolic syndrome and type 2 diabetes
One of the emergent nutritional strategies for improving multiple features of cardiometabolic diseases is the practice of intermittent fasting (IF), which consists of alternating periods of eating and fasting. IF can reduce circulating glucose and insulin levels, fat mass, and the risk of developing age-related pathologies. IF appears to upregulate evolution-conserved adaptive cellular responses, such as stress-response pathways, autophagy, and mitochondrial function. IF was also observed to modulate the circadian rhythms of hormones like insulin or leptin, among others, which levels change in conditions of food abundance and deficit. However, some contradictory results regarding the duration of the interventions and the anterior metabolic status of the participants suggest that more and longer studies are needed in order to draw conclusions. This review summarizes the current knowledge regarding the role of IF in the modulation of mechanisms involved in type 2 diabetes, as well as the risks.
Structure of the insulin receptor-insulin complex by single-particle cryo-EM analysis
The insulin receptor is a dimeric protein that has a crucial role in controlling glucose homeostasis, regulating lipid, protein and carbohydrate metabolism, and modulating brain neurotransmitter levels. Insulin receptor dysfunction has been associated with many diseases, including diabetes, cancer and Alzheimer's disease. The primary sequence of the receptor has been known since the 1980s, and is composed of an extracellular portion (the ectodomain, ECD), a single transmembrane helix and an intracellular tyrosine kinase domain. Binding of insulin to the dimeric ECD triggers auto-phosphorylation of the tyrosine kinase domain and subsequent activation of downstream signalling molecules. Biochemical and mutagenesis data have identified two putative insulin-binding sites, S1 and S2. The structures of insulin bound to an ECD fragment containing S1 and of the apo ectodomain have previously been reported, but details of insulin binding to the full receptor and the signal propagation mechanism are still not understood. Here we report single-particle cryo-electron microscopy reconstructions of the 1:2 (4.3 ?) and 1:1 (7.4 ?) complexes of the insulin receptor ECD dimer with insulin. The symmetrical 4.3 ? structure shows two insulin molecules per dimer, each bound between the leucine-rich subdomain L1 of one monomer and the first fibronectin-like domain (FnIII-1) of the other monomer, and making extensive interactions with the α-subunit C-terminal helix (α-CT helix). The 7.4 ? structure has only one similarly bound insulin per receptor dimer. The structures confirm the binding interactions at S1 and define the full S2 binding site. These insulin receptor states suggest that recruitment of the α-CT helix upon binding of the first insulin changes the relative subdomain orientations and triggers downstream signal propagation.
Peripheral Aβ acts as a negative modulator of insulin secretion
Type 2 diabetes mellitus is known to be a risk factor for Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. In AD, the cerebral accumulation of amyloid β (Aβ) triggers a pathological cascade leading to neurodegeneration. Plasma Aβ levels are thought to reflect the brain amyloid pathology and currently used as a diagnostic biomarker of AD. However, amyloid precursor protein and Aβ-generating enzymes, β- and γ-secretases, are widely expressed in various peripheral tissues. Previous reports have shown that glucose and insulin loading cause a transient increase of plasma Aβ in mice and humans. These findings led us to speculate that plasma Aβ is produced from glucose- and insulin-susceptible peripheral tissues to play a role in glucose and insulin metabolism. To test this hypothesis, we investigated the effects of glucose and insulin on Aβ secretion and the effect of Aβ on insulin secretion in vivo, ex vivo, and in vitro. Aβ was found to be secreted from β-cells of the pancreas along with insulin upon glucose stimulation. Upon insulin stimulation, Aβ was secreted from cells of insulin-targeted organs, such as adipose tissues, skeletal muscles, and the liver, along with their organokines. Furthermore, Aβ inhibited the glucose-triggered insulin secretion from β-cells, slowing down glucose clearance from the blood. These results suggest that peripheral Aβ acts as a negative modulator of insulin secretion. Our findings provide a possible mechanism linking diabetes to AD and call attention to how plasma Aβ levels are used in AD diagnosis.