2011
DOI: 10.1126/scitranslmed.3002669
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Amelioration of Type 2 Diabetes by Antibody-Mediated Activation of Fibroblast Growth Factor Receptor 1

Abstract: Clinical use of recombinant fibroblast growth factor 21 (FGF21) for the treatment of type 2 diabetes and other disorders linked to obesity has been proposed; however, its clinical development has been challenging owing to its poor pharmacokinetics. Here, we describe an alternative antidiabetic strategy using agonistic anti-FGFR1 (FGF receptor 1) antibodies (R1MAbs) that mimic the metabolic effects of FGF21. A single injection of R1MAb into obese diabetic mice induced acute and sustained amelioration of hypergl… Show more

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Cited by 157 publications
(188 citation statements)
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“…Mice lacking KLB are resistant to both acute and chronic effects of FGF21. However, the acute insulin-sensitizing effects of FGF21 are also absent in mice with specific deletion of adipose KLB (32) or FGFR1 (33), consistent with the notion that direct adipose tissue activation is required for FGF21 action (34).…”
supporting
confidence: 73%
“…Mice lacking KLB are resistant to both acute and chronic effects of FGF21. However, the acute insulin-sensitizing effects of FGF21 are also absent in mice with specific deletion of adipose KLB (32) or FGFR1 (33), consistent with the notion that direct adipose tissue activation is required for FGF21 action (34).…”
supporting
confidence: 73%
“…Recent evidence suggests that these beneficial effects observed with FGF21 or FGF19 treatment are not mediated through FGFR4 but distinctly through the FGFR1c/ ␤ Klotho complex. For example, treatment of mice with an FGF molecule biased toward the FGFR1c/ ␤ Klotho receptor complex or FGFR1 agonist antibody can recapitulate metabolic phenotypes induced by FGF19 and FGF21, including improvement of hyperglycemia and hyperlipidemia ( 14,28 ). These effects were absent in lipoatrophic animals ( 28 ), suggesting FGFR1 in adipose tissue is the main target of FGF21 action.…”
Section: Discussionmentioning
confidence: 99%
“…Besides, ablation of FGFR1 in adipose tissue resulted in impaired lipid profile [15]. Moreover, FGFR1 agonist treated diabetic mice exhibited improvement of hyperglycemia, hyperlipidemia, and hepatosteatosis [16]. Therefore, rescuing FGFR1 signaling would provide opportunity to reverse T2DM.…”
Section: Enzyme Linked Immunosorbent Assaymentioning
confidence: 99%