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Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

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Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
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Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
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Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

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Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
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Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
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Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
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スナップショット:インスリン/IGF1シグナル伝達

David K G Ma1, Christian Stolte2, James R Krycer3

  • 1Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia; School of Computer Science and Engineering, UNSW Sydney, NSW 2052, Australia.

Cell
|May 11, 2015
PubMed
まとめ

インスリン/IGF1シグナル伝達経路 (ISP) は,長期的な健康と寿命にとって極めて重要です. その失調は,2型糖尿病や老化プロセスなどの病気と関連しています.

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Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
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科学分野:

  • バイオケミストリー バイオケミストリー
  • 分子生物学は分子生物学である.
  • 遺伝学 遺伝学とは

背景:

  • インスリン/IGF1シグナル伝達経路 (ISP) は,基本的な生物学的プロセスを調節する保存された細胞経路です.
  • ISPの乱れは,老化,タイプ2糖尿病のような代謝疾患,種間の寿命決定に関与しています.

研究 の 目的:

  • 長期の健康と寿命の規制におけるISPの役割を明らかにする.
  • ISPの干渉が生物学的プロセスと疾患状態にどのように影響するかを理解する.
  • ISPによる規制のメカニズム,特にタンパク質のリン酸化ネットワークを調査する.

主な方法:

  • 異なる生物体におけるインスリン/IGF1シグナル伝達経路 (ISP) を調査した.
  • ISPの混乱が寿命と健康に与える影響を分析した.
  • エネルギー貯蔵,アポトーシス,転写を含む生物学的プロセスの調節を調べた.
  • ISPシグナル伝達におけるタンパク質リン酸化ネットワークの役割を研究した.

主要な成果:

  • ISPは,長期的な健康を維持するために不可欠であり,寿命を左右します.
  • 特定のISPの変化は,2型糖尿病とモデル生物の寿命の延長に関連しています.
  • ISPは,エネルギー貯蔵,アポトーシス,転写,ホメオスタシスなどの重要な細胞機能を支配する.
  • タンパク質リン酸化ネットワークにおける時間的な出来事は,ISPによって正確に再配線されます.

結論:

  • インスリン/IGF1シグナル伝達経路は,健康と寿命の重要な決定因子です.
  • ISPの規制を理解することは,老化と代謝疾患に関する洞察を提供します.
  • タンパク質のリン酸化ダイナミクスの正確な制御は,ISPの機能の中心です.