Abstract | BACKGROUND: METHODS: Liver-specific C57BL/6J.AlbCre+Cc1fl/fl mice were generated and their metabolic phenotype was characterized by comparison to that of their littermate controls at 2-9 months of age, using hyperinsulinemic-euglycemic clamp analysis and indirect calorimetry. The effect of hyperphagia on insulin resistance was assessed by pair-feeding experiments. RESULTS: CONCLUSION: AlbCre+Cc1fl/fl mutants provide an in vivo demonstration of the key role of impaired hepatic insulin clearance and hyperinsulinemia in the pathogenesis of secondary hepatic insulin resistance independently of lipolysis. They also reveal an important role for the liver-hypothalamic axis in the regulation of energy balance and subsequently, systemic insulin sensitivity.
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Authors | Hilda E Ghadieh, Lucia Russo, Harrison T Muturi, Simona S Ghanem, Iyad H Manaserh, Hye Lim Noh, Sujin Suk, Jason K Kim, Jennifer W Hill, Sonia M Najjar |
Journal | Metabolism: clinical and experimental
(Metabolism)
Vol. 93
Pg. 33-43
(04 2019)
ISSN: 1532-8600 [Electronic] United States |
PMID | 30664851
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2019 Elsevier Inc. All rights reserved. |
Chemical References |
- Carcinoembryonic Antigen
- Ceacam1 protein, mouse
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Topics |
- Animals
- Carcinoembryonic Antigen
(genetics)
- Glucose Clamp Technique
- Hyperinsulinism
(complications)
- Hyperphagia
(complications)
- Hypothalamus
(metabolism)
- Insulin Resistance
- Lipolysis
- Liver
(metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
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