Antidiabetic drug therapy alleviates type 1 diabetes in mice by promoting pancreatic α-cell transdifferentiation.

Antidiabetic drug therapy alleviates type 1 diabetes in mice by promoting pancreatic α-cell transdifferentiation. Biochem Pharmacol. 2020 Sep 11;:114216 Authors: Sarnobat D, Moffett CR, Tanday N, Reimann F, Gribble FM, Flatt PR, I Tarasov A Abstract Gut incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance secretion of insulin in a glucose-dependent manner, predominantly by elevating cytosolic levels of cAMP in pancreatic β-cells. Successful targeting of the incretin pathway by several drugs, however, suggests the antidiabetic mechanism is likely to span beyond the acute effect on hormone secretion and include, for instance, stimulation of β-cell growth and/or proliferation. Likewise, the antidiabetic action of kidney sodium-glucose linked transporter-2 (SGLT-2) inhibitors exceeds simple increase glucose excretion. Potential reasons for these 'added benefits' may lie in the long-term effects of these signals on developmental aspects of pancreatic islet cells. In this work, we explored if the incretin mimetics or SGLT-2 inhibitors can affect the size of the islet α- or β-cell compartments, under the condition of β-cell stress. To that end, we utilised mice expressing YFP specifically in pancreatic α-cells, in which we modelled type 1 diabetes by injecting streptozotocin, followed by a 10-day administration of liraglutide, sitagliptin or dapagliflozin. We observed an onset of diab...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research