マウスのベータ細胞におけるFGFシグナル伝達の弱化は,糖尿病を引き起こす
A W Hart1, N Baeza, A Apelqvist
1Department of Microbiology and ULMM, Umeå University, Sweden.
Nature
|December 29, 2000
まとめ
フィブロブラスト成長因子受容体1c (FGFR1c) のシグナル伝達は,大人のマウスのベータ細胞機能を維持するために重要である. FGFR1cシグナル伝達の障害は,糖尿病を引き起こし,2型糖尿病の特徴を模倣する.
科学分野:
- エンドクリノロジー エンドクリノロジー
- 分子生物学は分子生物学である.
- 糖尿病に関する研究
背景:
- 線維細胞成長因子 (FGF) 信号伝達は,臓器の発達と細胞の分化に役割を果たします.
- FGFのシグナル伝達成分は,大人のマウスのベータ細胞で発現し,分化細胞での役割を示唆しています.
研究 の 目的:
- 成人マウスのベータ細胞機能におけるFGFシグナル伝達,特にFGFR1cおよびFGFR2bの役割を調査する.
- グルコースホメオスタシスにおけるFGFR1シグナル伝達とホメオボックス遺伝子Ipf1/Pdx1との関係を決定する.
主な方法:
- 成人マウスのベータ細胞におけるFGFリガンドと受容体の発現分析.
- FGFR1cおよびFGFR2bのシグナル伝達が,マウスの臓における支配的陰性受容体発現を用いて混乱する.
- 糖尿病のフェノタイプ,ベータ細胞数,グルコーストランスポーター2,プロインスリン,プロホルモンコンバーターゼ発現の評価.
主要な成果:
- マウスのFGFR1cシグナルが弱く,FGFR2bシグナルが弱くならないことが,年齢依存型糖尿病を引き起こした.
- FGFR1cのシグナル伝達欠乏は,ベータ細胞数の減少,グルコーストランスポーター2の発現障害,およびプロインスリン含有量の増加をもたらしました.
- Ipf1/Pdx1は,ベータ細胞におけるFGFR1シグナル伝達成分発現に不可欠であり,グルコース感知とインスリン処理を制御するために上流的に作用します.
結論:
- FGFR1cのシグナル伝達は,成人のマウスのベータ細胞機能の微分化とグルコースホメオスタシスの維持に不可欠です.
- FGFR1cシグナル伝達の欠陥は,2型糖尿病の主要な病理学的特徴を模倣する.
- Ipf1/Pdx1は,FGFR1のシグナル伝達に先行して作用し,ベータ細胞機能の重要な規制経路を強調する.
関連する概念動画
Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Glucose Transporters
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
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 co-secreted in...
Insulin and C-peptide are co-secreted in...
Diabetic Neuropathy
DefinitionDiabetic neuropathy is nerve damage caused by long-standing diabetes mellitus. It results directly from prolonged high blood sugar levels.PathophysiologyThe pathophysiology of diabetic neuropathy involves both metabolic and vascular disturbances triggered by chronic hyperglycemia.Metabolic injury: Elevated glucose levels activate the polyol pathway within nerve cells, leading to the accumulation of sorbitol and fructose. This increases oxidative stress, disrupts normal nerve...


