関連する実験動画
Updated: May 13, 2026

11:10
Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
禁食誘導スイッチは,アクティベーター/コアクティベーターの交換を通じてグルコネオゲネシスを調節します
Yi Liu1, Renaud Dentin, Danica Chen
1The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, California 92037, USA.
Nature
|October 14, 2008
まとめ
断食は,CRTC2とFOXO1.1を切り替えることでエネルギーバランスを調節します. Sirtuin 1 (SIRT1) はCRTC2を脱エチレートし,FOXO1の活性を促進し,長期間の断食中にグルコースホメオスタシスを維持します.
科学分野:
- メタボリック調節 メタボリック調節
- 分子内分泌学は分子内分泌学である.
- 栄養素を感知する.
背景:
- 断食はグルカゴン経由で肝臓のグルコネオゲネシスを誘発し,CRTC2とFOXO1.1が関与する.
- インスリンシグナル伝達が低下し,断食中にグルコネオゲネシスが増加します.
- ケトン体は,遅期の断食中に補償燃料を提供する.
研究 の 目的:
- 断食中のエネルギーバランスの維持におけるp300とSIRT1の役割を調査する.
- CRTC2とFOXO1.1の連続的な誘導と調節を解説する.
主な方法:
- 肝臓特異性Sirt1遺伝子ノックアウトによるマウスモデルを使用した.
- 投与されたSIRT1アンタゴニストおよびアゴニスト.
- 評価されたタンパク質の脱酸化,アセチル化,およびユビキチネーション.
- 測定されたグルコーネオゲン遺伝子発現とグルコース出力.
主要な成果:
- 断食は,CRTC2とFOXO1.1を調節するためにp300とSIRT1を巻き込むスイッチを誘発します.
- p300はCRTC2をアセチラ化して活性化し,SIRT1はCRTC2をデセチラ化してダウンレギュレーションする.
- SIRT1の活性化により,FOXO1とPGC-1alphaが相互に活性化されます.
- SIRT1を阻害すると,CRTC2の活性とグルコースの出力が増加する.
結論:
- p300とSIRT1の断食誘導スイッチは,エネルギーバランスを維持する.
- このスイッチによるCRTC2とFOXO1の連続的な活性化は,グルコースホメオスタシスにとって極めて重要です.
- SIRT1は,断食中のグルコン生成の調節に重要な役割を果たします.
さらに関連する動画
関連する概念動画
cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Hormones Regulating Blood Glucose
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...
In addition to accelerating glucose uptake and utilization, insulin has...
Metabolic States of the Body: The Postabsorptive State
The postabsorptive state usually starts about four hours after a meal and lasts until the next meal is eaten. During this time, the digestive system stops absorbing nutrients, and the body uses stored energy reserves to maintain stable blood glucose levels.
Initially, glycogen stored in the liver is broken down to release glucose into the bloodstream, while glycogen in the muscles is broken down to supply glucose for energy directly within the muscle cells. As glycogen stores diminish,...
Initially, glycogen stored in the liver is broken down to release glucose into the bloodstream, while glycogen in the muscles is broken down to supply glucose for energy directly within the muscle cells. As glycogen stores diminish,...
Metabolic States of the Body: Fasting and Starvation
During the initial hours of fasting, the body uses up its glycogen stores as an energy source. Once these glycogen reserves are depleted, the body begins breaking down stored triglycerides and structural proteins. During this stage, glycerol becomes a key substrate for gluconeogenesis, while free fatty acids undergo beta-oxidation to provide energy for tissues, such as skeletal muscle. In the fasting state, the body spares protein breakdown as much as possible to conserve muscle and structural...
Glucose Homeostasis: Regulation of Blood Glucose
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
Inducible Operons: lac Operon
The lac operon in Escherichia coli is a model for understanding inducible gene regulation and metabolic flexibility. It integrates local control by lactose and global regulation through catabolite repression, enabling E. coli to preferentially metabolize glucose when available and switch to lactose utilization when glucose is scarce.Structure and Function of the lac OperonThe lac operon contains three structural genes: lacZ (β-galactosidase), lacY (lactose permease), and lacA (thiogalactoside...

