Antidiabetic Effects of IGFBP2, a Leptin-Regulated Gene

Hedbacker, Kristina; Birsoy, Kıvanç; Wysocki, Robert W.; Asilmaz, Esra; Ahima, Rexford S.; Farooqi, I. Sadaf; Friedman, Jeffrey M.

doi:10.1016/j.cmet.2010.02.010

Cited by 11 publications

(21 citation statements)

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“…This observation was further validated by acute IGFBP2 overexpression in ob/ob , type 1 and type 2 diabetic mice, using adenoviral infection, and in all cases plasma glucose and insulin levels were reduced. This improved glycemic control, which was independent of weight loss and food intake, was also observed in leptin-resistant animals, confirming that IGFBP2 acts downstream of leptin action [90]. These findings provide additional rationale for considering IGFBP-2 as a cancer therapeutic by underscoring the reduced diabetic symptoms IGFBP-2 therapy would likely have.…”

Section: Anti-diabetic Effects Of Igfbp-2supporting

confidence: 54%

“…A recent microarray analysis of leptin action revealed up-regulation of IGFBP2 in the livers of leptin vs . vehicle treated ob/ob mice [90]. This observation was further validated by acute IGFBP2 overexpression in ob/ob , type 1 and type 2 diabetic mice, using adenoviral infection, and in all cases plasma glucose and insulin levels were reduced.…”

Section: Anti-diabetic Effects Of Igfbp-2mentioning

confidence: 81%

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Defining the pathway to insulin-like growth factor system targeting in cancer

Rosenzweig

Atreya

2010

Biochemical Pharmacology

111

109

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The insulin-like growth factors (IGFs; IGF-1 and IGF-2) play central roles in cell growth, differentiation, survival, transformation and metastasis. The biologic effects of the IGFs are mediated by the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase with homology to the insulin receptor (IR). Dysregulation of the IGF system is well recognized as a key contributor to the progression of multiple cancers, with IGF-1R activation increasing the tumorigenic potential of breast, prostate, lung, colon and head and neck squamous cell carcinoma (HNSCC). Despite this relationship, targeting the IGF-1R has only recently undergone development as a molecular cancer therapeutic. As it has taken hold, we are witnessing a robust increase and interest in targeting the inhibition of IGF-1R signaling. This is accentuated by the list of over 30 drugs, including monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) that are under evaluation as single agents or in combination therapies [1]. The IGF binding proteins (IGFBPs) represent the third component of the IGF system consisting of a class of six soluble secretory proteins. They represent a unique class of naturally occurring IGF antagonists that bind to and sequester IGF-1 and IGF-2, inhibiting their access to the IGF-1R. Due to their dual targeting of the IGFs without affecting insulin action, the IGFBPs are an untapped "third" class of IGF-1R inhibitors. In this commentary, we highlight some of the significant aspects of and prospects for targeting the IGF-1R and describe what the future may hold.

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Section: Anti-diabetic Effects Of Igfbp-2supporting

confidence: 54%

Section: Anti-diabetic Effects Of Igfbp-2mentioning

confidence: 81%

Defining the pathway to insulin-like growth factor system targeting in cancer

Rosenzweig

Atreya

2010

Biochemical Pharmacology

111

109

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“…Another approach is varying dosage of myostatin or its inhibitors. For example, leptin's regulation of glucose metabolism has been uncoupled from its regulation of fat mass by using low dose injections that do not affect body weight [130]. An analogous approach using low doses of myostatin antagonists or myostatin itself may allow us to begin to address these questions.…”

Section: Resultsmentioning

confidence: 99%

Metabolic Functions of Myostatin and GDF11

McPherron¹

2010

IEMAMC

109

107

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Myostatin is a member of the transforming growth factor β superfamily of secreted growth factors that negatively regulates skeletal muscle size. Mice null for the myostatin gene have a dramatically increased mass of individual muscles, reduced adiposity, increased insulin sensitivity, and resistance to obesity. Myostatin inhibition in adult mice also increases muscle mass which raises the possibility that anti-myostatin therapy could be a useful approach for treating diseases such as obesity or diabetes in addition to muscle wasting diseases. In this review I will describe the present state of our understanding of the role of myostatin and the closely related growth factor growth/differentiation factor 11 on metabolism.

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“…Analysis of liver mRNA using microarrays identified IGF binding protein 2 (IGFBP2) as being regulated by leptin. Overexpression of IGFBP2 via adenovirus reversed diabetes in ob/ob, as well as agouti (Ay/a) and diet-induced obese mice [42]. These results show that leptin-inducible IGFBP2 can regulate glucose metabolism, a finding with potential implications for the treatment of diabetes.…”

Section: Other Actions Of Leptinmentioning

confidence: 65%

“…Although the brain is the major site of leptin action, low levels of LRb are expressed in peripheral tissues and involved in metabolism. Leptin normalizes plasma glucose and insulin in ob/ob mice without significantly reducing body weight [42]. Analysis of liver mRNA using microarrays identified IGF binding protein 2 (IGFBP2) as being regulated by leptin.…”

Section: Other Actions Of Leptinmentioning

confidence: 99%