Deletion of the glucagon receptor gene before and after experimental diabetes reveals differential protection from hyperglycemia.

ABSTRACT:

Objective

Mice with congenital loss of the glucagon receptor gene (Gcgr^-/- mice) remain normoglycemic in insulinopenic conditions, suggesting that unopposed glucagon action is the driving force for hyperglycemia in Type-1 Diabetes Mellitus (T1DM). However, chronic loss of GCGR results in a neomorphic phenotype that includes hormonal signals with hypoglycemic activity. We combined temporally-controlled GCGR deletion with pharmacological treatments to dissect the direct contribution of GCGR signaling to glucose control in a common mouse model of T1DM.

Methods

We induced experimental T1DM by injecting the beta-cell cytotoxin streptozotocin (STZ) in mice with congenital or temporally-controlled Gcgr loss-of-function using tamoxifen (TMX).

Results

Disruption of

SUBMITTER: Rivero-Gutierrez B 

PROVIDER: S-EPMC6197675 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature