Synergy Between Gαz Deficiency and GLP-1 Analog Treatment in Preserving Functional β-Cell Mass in Experimental Diabetes

摘要: A defining characteristic of type 1 diabetes mellitus (T1DM) pathophysiology is pancreatic β-cell death and dysfunction, resulting in insufficient insulin secretion to properly control blood glucose levels. Treatments that promote replication survival, thus reversing the loss mass, while also preserving function, could lead a real cure for T1DM. The α-subunit heterotrimeric Gz protein, Gαz, tonic negative regulator adenylate cyclase downstream cAMP production. one few identified signaling molecules can simultaneously have positive impact on islet proliferation, function. purpose our study was determine whether mice lacking Gαz might be protected, at least partially, from dysfunction after streptozotocin treatment. We aimed act concert with an activator cAMP-stimulatory glucagon-like peptide receptor, exendin-4 (Ex4). Without Ex4 treatment, Gαz-null still developed hyperglycemia, albeit delayed. same finding held true wild-type treated Ex4. With were protected developing severe hyperglycemia. Immunohistological studies performed pancreas sections vitro apoptosis, cytotoxicity, survival assays demonstrated clear effect death; function improved islets. These data support hypothesis combination therapies targeting both stimulatory inhibitory pathways will more effective than either alone protecting, preserving, possibly regenerating mass