Control of Pancreatic β Cell Regeneration by Glucose Metabolism

被引：273

作者：

Porat, Shay ^{[2
,4
]}

Weinberg-Corem, Noa ^{[2
]}

Tomovsky-Babaey, Sharona ^{[1
]}

Schyr-Ben-Haroush, Rachel ^{[1
,2
]}

Hija, Ayat ^{[2
]}

Stolovich-Rain, Miri ^{[2
]}

Dadon, Daniela ^{[2
]}

Granot, Zvi ^{[2
]}

Ben-Hur, Vered ^{[3
]}

White, Peter ^{[5
,6
]}

Girard, Christophe A. ^{[7
]}

Karni, Rotem ^{[3
]}

Kaestner, Klaus H. ^{[5
,6
]}

Ashcroft, Frances M. ^{[7
]}

Magnuson, Mark A. ^{[8
,9
]}

Saada, Ann ^{[10
]}

Grimsby, Joseph ^{[11
]}

Glaser, Benjamin ^{[1
]}

Dor, Yuval ^{[2
]}

机构：

[1] Hadassah Hebrew Univ Med Ctr, Dept Internal Med, Endocrinol & Metab Serv, IL-91120 Jerusalem, Israel

[2] Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel

[3] Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Biochem & Mol Biol, IL-91120 Jerusalem, Israel

[4] Hadassah Hebrew Univ Med Ctr, Dept Obstet & Gynecol, IL-91240 Jerusalem, Israel

[5] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA

[6] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA

[7] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England

[8] Vanderbilt Univ, Sch Med, Ctr Stem Cell Biol, Nashville, TN 37232 USA

[9] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

[10] Hadassah Hebrew Univ Med Ctr, Dept Genet & Metab Dis, IL-91120 Jerusalem, Israel

[11] Hoffmann La Roche Inc, Dept Metab Dis, Nutley, NJ 07110 USA

来源：

CELL METABOLISM | 2011年 / 13卷 / 04期

基金：

英国惠康基金;

关键词：

INSULIN-RESISTANCE; GLUCOKINASE MUTATION; COMPENSATORY GROWTH; PRIMARY MECHANISM; DIABETES THERAPY; ADULT-RATS; IN-VIVO; REPLICATION; MICE; MASS;

D O I：

10.1016/j.cmet.2011.02.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Recent studies revealed a surprising regenerative capacity of insulin-producing beta cells in mice, suggesting that regenerative therapy for human diabetes could in principle be achieved. Physiologic beta cell regeneration under stressed conditions relies on accelerated proliferation of surviving beta cells, but the factors that trigger and control this response remain unclear. Using islet transplantation experiments, we show that beta cell mass is controlled systemically rather than by local factors such as tissue damage. Chronic changes in beta cell glucose metabolism, rather than blood glucose levels per se, are the main positive regulator of basal and compensatory beta cell proliferation in vivo. Intracellularly, genetic and pharmacologic manipulations reveal that glucose induces beta cell replication via metabolism by glucokinase, the first step of glycolysis, followed by closure of K-ATP channels and membrane depolarization. Our data provide a molecular mechanism for homeostatic control of beta cell mass by metabolic demand.

引用

页码：440 / 449

页数：10

共 51 条

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Glucose infusion in mice -: A new model to induce β-cell replication [J].