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.2009.11.007

Cited by 280Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesGrowth Hormone and Insulin-like Growth Factors

Antidiabetic Effects of IGFBP2, a Leptin-Regulated Gene

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Hedbacker, Kristina, Birsoy, Kıvanç, Wysocki, Robert W., Asilmaz, Esra, Ahima, Rexford S., Farooqi, I. Sadaf, Friedman, Jeffrey M.·2010·Cell Metabolism

DOI 10.1016/j.cmet.2009.11.007

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Abstract

We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma glucose and insulin concentration. We found that a leptin dose of 12.5 ng/hr significantly lowers blood glucose and that 25 ng/hr of leptin normalizes plasma glucose and insulin without significantly reducing body weight, establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 (IGFBP2) as being regulated by leptin with a similarly high potency. Overexpression of IGFBP2 by an adenovirus reversed diabetes in insulin-resistant ob/ob, Ay/a, and diet-induced obese mice, as well as insulin-deficient streptozotocin-treated mice. Hyperinsulinemic clamp studies showed a 3-fold improvement in hepatic insulin sensitivity following IGFBP2 treatment of ob/ob mice. These results show that IGFBP2 can regulate glucose metabolism, a finding with potential implications for the pathogenesis and treatment of diabetes.

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Leptin administration to leptin-deficient mice or humans ameliorates hyperglycemia and hyperinsulinemia even when differences in food intake are controlled by pair-feeding.
“leptin administration to leptin-deficient mice or humans ameliorates hyperglycemia and hyperinsulinemia (60, 141) even when differences of food intake are controlled by pair-feeding (80, 158).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [80]

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Authors: Hedbacker, K., Birsoy, K., Wysocki, R. W., Asilmaz, E., Ahima, R. S., Farooqi, I. S., & Friedman, J. M.
Affiliations: Rockefeller University (US)
Howard Hughes Medical Institute (US)
University of Pennsylvania (US)
University of Cambridge (GB)
Corresponding author: Friedman, Jeffrey M.
ORCID: Hedbacker, Kristina
Birsoy, Kıvanç
Wysocki, Robert W.
Ahima, Rexford S.
Farooqi, I. Sadaf
Friedman, Jeffrey M.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2010-01
Volume: 11
Issue: 1
Pages: 11-22
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2009.11.007
OpenAlex: W1970142642
Semantic Scholar: ac52e45d444bd4b908d42df05c555b9bf5a2225e
Cited by: 280
References: 80
Citations by year: 2026: 12 · 2025: 8 · 2024: 18 · 2023: 16 · 2022: 9 · 2021: 16 · 2020: 23 · 2019: 13 · 2018: 19 · 2017: 14 · 2016: 17 · 2015: 15 · 2014: 27 · 2013: 20 · 2012: 17
FWCI: 10.55
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1293 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust (082390)
National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK 19525, P30DK019525)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords: IGFBP-2, leptin, diabetes mellitus, glucose metabolism, insulin sensitivity, hepatic insulin sensitivity, ob/ob mice, diet-induced obesity, streptozotocin-induced diabetes, insulin resistance, adenoviral overexpression
MeSH terms: Adenoviridae, Animals, Blood Glucose, Humans, Hyperglycemia, Hyperinsulinism, Hypoglycemic Agents, Insulin, Liver, RNA, Messenger, Gene Transfer Techniques, Mice, Knockout, Insulin-Like Growth Factor Binding Protein 2, Oligonucleotide Array Sequence Analysis, Leptin, Mice

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Antidiabetic Effects of IGFBP2, a Leptin-Regulated Gene

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