Universität zu Köln

Gahete, Manuel D. ORCID: 0000-0002-4578-2179, Cordoba-Chacon, Jose ORCID: 0000-0001-8787-2706, Anadumaka, Chike V., Lin, Qing, Bruening, Jens C., Kahn, C. Ronald, Luque, Raul M. ORCID: 0000-0002-7585-1913 and Kineman, Rhonda D. (2011). Elevated GH/IGF-I, Due to Somatotrope-Specific Loss of Both IGF-I and Insulin Receptors, Alters Glucose Homeostasis and Insulin Sensitivity in a Diet-Dependent Manner. Endocrinology, 152 (12). S. 4825 - 4838. CHEVY CHASE: ENDOCRINE SOC. ISSN 1945-7170

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Abstract

A unique mouse model was developed with elevated endogenous GH (2- to 3-fold) and IGF-I (1.2- to 1.4-fold), due to somatotrope-specific Cre-mediated inactivation of IGF-I receptor (IgfIr) and insulin receptor (Insr) genes (IgfIr, Insr(rGHpCre), referred to as HiGH mice). We demonstrate that the metabolic phenotype of HiGH mice is diet dependent and differs from that observed in other mouse models of GH excess due to ectopic heterologous transgene expression or pituitary tumor formation. Elevated endogenous GH promotes lean mass and whole-body lipid oxidation but has minimal effects on adiposity, even in response to diet-induced obesity. When caloric intake is moderated, elevated GH improves glucose clearance, despite low/normal insulin sensitivity, which may be explained in part by enhanced IGF-I and insulin output. However, when caloric intake is in excess, elevated GH promotes hepatic lipid accumulation, insulin resistance, hyperglycemia, and ketosis. The HiGH mouse model represents a useful tool to study the role endogenous circulating GH levels play in regulating health and disease. (Endocrinology 152: 4825-4837, 2011)

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gahete, Manuel D. UNSPECIFIED orcid.org/0000-0002-4578-2179 UNSPECIFIED Cordoba-Chacon, Jose UNSPECIFIED orcid.org/0000-0001-8787-2706 UNSPECIFIED Anadumaka, Chike V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lin, Qing UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kahn, C. Ronald UNSPECIFIED UNSPECIFIED UNSPECIFIED Luque, Raul M. UNSPECIFIED orcid.org/0000-0002-7585-1913 UNSPECIFIED Kineman, Rhonda D. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-484483
DOI:	10.1210/en.2011-1447
Journal or Publication Title:	Endocrinology
Volume:	152
Number:	12
Page Range:	S. 4825 - 4838
Date:	2011
Publisher:	ENDOCRINE SOC
Place of Publication:	CHEVY CHASE
ISSN:	1945-7170
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HORMONE-TRANSGENIC MICE; GROWTH-FACTOR-I; HIGH-FAT DIET; BODY-COMPOSITION; FUSION GENES; ENERGY-EXPENDITURE; PROTEIN-METABOLISM; BINDING-PROTEINS; INDUCED OBESITY; ADIPOSE-TISSUE Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48448