Abstract
Background and aim β2-Adrenoceptors (β2-ARs) are G protein-coupled receptors (GPCRs) expressed in the major insulin target tissues. The interplay between β2-AR and insulin pathways is involved in the maintenance of glucose homeostasis. The aim of this study was to explore the consequences of β2-ARs deletion on insulin sensitivity and insulin signaling cascade in metabolically active tissues. Methods and results We evaluated glucose homeostasis in skeletal muscle and liver of β2-AR-null mice (β2-AR−/−) by performing in vivo (glucose tolerance test and insulin tolerance test) and ex vivo (glucose uptake and glycogen determination) experiments. β2-AR gene deletion is associated with hepatic insulin resistance and preserved skeletal muscle insulin sensitivity. Importantly, we demonstrate that hepatic β2-AR regulates insulin-induced AKT activation via Grb2-mediated SRC recruitment through a Gi-independent mechanism. Conclusions β-AR stimulation contributes to the development of early stages of insulin resistance progression in the liver. Our findings indicate that the cross-talk between β2-AR and insulin signaling represents a fundamental target towards the development of novel therapeutic approaches to treat type 2 diabetes and metabolic syndrome.
Original language | English (US) |
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Pages (from-to) | 615-623 |
Number of pages | 9 |
Journal | Nutrition, Metabolism and Cardiovascular Diseases |
Volume | 27 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2017 |
Externally published | Yes |
Keywords
- AKT
- Insulin resistance
- SRC
- aPKCζ
- β adrenoceptors
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics
- Cardiology and Cardiovascular Medicine