Journal of Animal Research and Nutrition

Description

Glucagon like Peptide-1 (GLP-1) is a peptide hormone synthetized by intestinal "L" cells, which are located mainly in the most distal intestinal regions, such as the ileum and colon. This peptide is also produced in the Central Nervous System (CNS), more specifically in solitary tract nucleus, and in pancreatic α cells. The mechanisms that trigger GLP-1 release is quite like that of insulin. Increase in intracellular glucose leads to higher ATP synthesis, which in turn interacts with ATP sensitive K + channels, closing them. This leads to cell depolarization and the opening of Voltage Dependent Calcium Channels (VDCC), increasing this cation concentration in the cells. Finally, Ca++ interacts with vesicles containing GLP-1 and promotes its exocytosis.

Diabetes Melitus

GLP-1 has several important extra pancreatic functions and most of them depend on actions in the CNS. It increases satiety and thermogenesis, inhibits blood pressure rising, gastric emptying and water intake, is involved in the reward pathway and in the hypothalamic adrenal pituitary axis. GLP-1 also acts on the cardiovascular system, either directly binding to GLP-1R in cardio myocytes and vascular smooth muscle cells, and indirectly, by its CNS actions. Considering the increasing incidence of Diabetes Melitus (DM) and obesity in cats and dogs, the aim of this review is to summarize the available information about the physiological and pharmacological actions of GLP-1 in domestic animals and discuss about its potential applications in veterinary medicine.

Besides its acute effects, GLP-1 also has long-term effects on β cells that are mainly related to apoptosis inhibition and cellular multiplication. However, studies with diabetic human patients have not shown an increase in β cells proliferation. Pancreatic islets cells also express GLP-1R, therefore GLP1 binding can also inhibits glucagon and stimulates somatostatin release.

Much of the interest in GLP-1 is due to its action on pancreatic islets, however, it was described in rodents and humans that several other tissues express GLP-1R. GLP-1R has already been identified in the stomach, skeletal muscle, smooth muscle, atrial cardiac muscle, kidneys, lungs, adipose tissue and in several areas of the Central Nervous System (CNS).

Physiology and Biochemistry

Reductionist approaches in physiology and biochemistry are essential for understanding how animals cope and adapt to their environments. Transcriptomics is no longer restricted to a select few, and accessibility and affordability continue to facilitate its rapid growth as a science. Transcriptomes have been quantified under conditions of hypoxia, climate change, salinity, drought, environmental pollution, and ultraviolet radiation among others; these studies have greatly improved understanding of the molecular machinery required for organismal adaptation. These “snapshots in time” however are never complete as the transcriptome is exquisitely sensitive to an individual's current physiologic state. Animal physiologists new to the field must recognize limitations of transcriptome technologies and consider experimental designs that strengthen physiologic interpretation. Current estimates suggest that a sample size of 6 or more are required for RNA-seq experiments in order to capture the majority of differentially expressed genes confidently. Approaches for statistical analyses of data derived from RNA-seq should be explored, as studies continue to point out that high false discoveries rates are pervasive with RNA-seq studies, reminiscent of the early days of microarrays. Incorporating biological variability, rather than reducing it (pooling strategies), into experimental designs is essential. Moreover, real-time PCR must not be viewed as a “validation step” to justify low samples sizes, but rather an orthogonal method to strengthen biological interpretation. The use of proper experimental controls in transcriptomics studies (spike-in controls and technical replication) are recommended and there is a pressing need for inter-laboratory tests (round robin experiments) to quantify repeatability and to identify sources of transcriptome variation within the context of animal physiology. Testing the reproducibility of transcriptome experiments in light of physiology in non-model organisms would be a significant contribution to the community.

The data collected so far demonstrate that GLP-1 may have a species-specific action in dogs, being more insulinomimetic than insulinotropic, although the latter has already been observed. In cats, the physiological actions of GLP-1 seem like those considered classic in humans and rodents. In diabetic dogs, the use of drugs based on GLP-1 actions led to reduction in blood glucose and higher glucose uptake, while in diabetic cats there was a reduction in glycemic variability and in the need of exogenous insulin administration. Thus, available evidence indicates that GLP-1 based drugs could become alternatives to DM treatment in domestic animals. However, there are still many open points, and current data are surprisingly limited, not providing enough elements to recommend these drugs widespread clinical use.