Olfactory dysfunction in patients with type 2 diabetes can be counteracted with a drug that activates a hormone known as GLP-1R, according to recent research. The study, “Type 2 diabetes-induced neuronal pathology in the piriform cortex of the rat is reversed by the GLP-1 receptor agonist Exendin-4,” was published in the journal Oncotarget.
Evidence from recent studies confirmed a relationship between type 2 diabetes and olfactory dysfunction, as well as a correlation between lower olfactory scores and the presence of diabetic complications.
The piriform cortex (PC) is the largest of the olfactory cortical areas in the brain that receives direct input from the olfactory bulb through the lateral olfactory tract.
Dr. Grazyna Lietzau and colleagues at Sweden’s Karolinska Institutet, Department of Clinical Science and Education, hypothesized that olfactory dysfunction in type 2 diabetes was linked to a specific brain neuropathology. Since the PC brain area is involved in the regulation of olfaction, the research aimed to identify potential neuronal pathologies in the PC of aging type 2 diabetes rats.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-dependent insulin secretion through a GLP-1 receptor (GLP-1R). However, GLP-1 has a very short half-life due to rapid degradation. Exendin-4 (Ex-4) is a stable synthetic form of GLP-1 that has been developed for the treatment of type 2 diabetes.
Besides its anti-diabetic properties, Ex-4 can cross the blood brain barrier, with evidence supporting its neuroprotective role in several neurological disorders. As a result, the research team investigated the potential efficacy of Ex-4 against type 2 diabetes-induced neuronal pathology.
The researchers used young-adult and middle-age rats with type 2 diabetes and compared them to healthy age-matched rats. The team found that the middle-age type 2 diabetes rats had a neuronal pathology in the PC brain area, which explained the olfactory dysfunction.
These rats with type 2 diabetes (T2D) were then treated for six weeks with Ex-4, and the treatment was able to reverse the neuronal pathology in the animals.
“We believe to have identified one important factor at the basis of olfactory dysfunction in type 2 diabetes. We also showed that the identified neuropathology in the PC could be substantially counteracted by GLP-1R activation,” the research team concluded in their article. “Whether reversing the PC-related neuronal pathology in the T2D brain could represent a potential pharmacological target to treat olfactory dysfunction in diabetic patients or to even delay T2D-related brain complications remains to be determined.”