Search bioRxiv⌕ Search

Biology subjects

Caicedo, A.

Publications and source records attributed to Caicedo, A..

4 recordsLinked to original sources

Urbanization and altitude impact on gut microbiome of an Andean frog (Pristimantis unistrigatus)

The analysis of the intestinal microbiome in amphibians provides insights of the anthropogenic environmental impact. Pristimantis unistrigatus is an Andean amphibian species whose distribution has been recorded in Ecuador and Colombia, ranging from endemic elfin forests to urban gardens. In this study, we focus on the analysis of the P. unistrigatus microbiome 16S rRNA gene sequencing. A total of 32 specimens of P. unistrigatus were collected and analyzed from 4 locations in the Valley of Quito, Ecuador, characterized by several urban environments and altitudes. The results show that the relative abundance of bacteria is significantly different amongst groups. Clostridiales are proportionally more abundant in rural and lower altitude locations, while Erysipelotrichaceae, Desulfovibrionaceae, Enterobacteriaceae, Bacteroidaceae and Lachnospiraceae are found at higher elevations. These results highlight the importance of the evolution of the microbiome as a tool of adaptation and survival of amphibians in the present-day changing ecosystems undergoing anthropogenic stresses. ImportanceAmphibians constitutes one of the groups most vulnerable to environmental alterations. Due to their sophisticated reproductive and breeding requirements and their permeable skins to breathe, amphibians are compulsively studied as ecological indicators. The destruction of pristine habitats occurred all over the planet in recent decades has caused a catastrophic decline in amphibian populations for many species everywhere. Ecuador, being one of the most biodiverse country on Earth, hosts a huge variety of amphibians, thus offering a unique possibility of studying the biology of the amphibian species living in its ecosystems, and how they adapt to changing habitats. A direct way to diagnose the status of an amphibian population is to study the gut microbiome of the individual specimens. The gut microbiome is closely related to the hosts health and so to its ability to adapt and survive. An important output of this study is to offer indications and tools useful to conservation programs before irreversible damages are caused to the habitats and the amphibians populations still thriving in them.

ecology↗

Pericyte control of pancreatic islet blood flow impacts glucose homeostasis

The pancreatic islet depends on blood supply to efficiently sense plasma glucose levels and deliver insulin and glucagon into the circulation. Long thought to be passive conduits of nutrients and hormones, islet capillaries were recently found to be densely covered with contractile pericytes, suggesting local control of blood flow. Here we determined the contribution of islet pericytes to the regulation of islet blood flow, plasma insulin and glucagon levels, and glycemia. Selective optogenetic activation of pericytes in intraocular islet grafts contracted capillaries and diminished blood flow. In awake mice, acute clamping of islet blood flow by optogenetic or pharmacological activation of pericytes disrupted hormonal responses, glycemia, and glucose tolerance. Our findings indicate that pericytes mediate vascular responses in the islet that are required for adequate hormone secretion and glucose homeostasis. Vascular deficiencies commonly seen in the islets of people with type 2 diabetes may impair regulation of islet blood flow and thus precipitate islet dysfunction.

physiology↗

FAILURE OF PANCREATIC ALPHA CELLS TO RESPOND TO HYPOGLYCEMIA IS LINKED TO IMPAIRED GLUTAMATE RECEPTOR SIGNALING IN DIABETES

Glucagon secretion from pancreatic alpha cells is crucial to prevent hypoglycemia. For reasons still unknown, people with type 1 diabetes lose this glucoregulatory mechanism and are susceptible to dangerous hypoglycemia. Here we show that alpha cells in living pancreas slices from donors with type 1 diabetes failed to secrete glucagon in response to decreases in glucose concentration, thus mirroring the in vivo unresponsiveness to hypoglycemia. Glucagon content and responses to KCl depolarization were not affected, suggesting that alpha cells retained their secretory potential. By contrast, alpha cells had severely impaired signaling via glutamate receptors of the AMPA/kainate type. Under healthy conditions, activating these receptors was required to elicit full glucagon responses to decreases in glucose levels. In type 1 diabetes, reactivating residual glutamate receptor function with the positive allosteric modulators cyclothiazide and aniracetam restored glucagon secretion in response to hypoglycemia. These positive allosteric modulators are already approved to treat other conditions and could be repurposed to prevent hypoglycemia and improve management of diabetes.

physiology↗

PANCREATIC ISLETS COMMUNICATE WITH THE BRAIN VIA VAGAL SENSORY NEURONS

Depleting visceral sensory nerves affects pancreatic islet function, glucose metabolism and diabetes onset, but how islet endocrine cells interact with sensory neurons has not been studied. Here we show that the pancreatic islet is innervated by vagal sensory axons expressing substance P, calcitonin-gene related peptide, and serotonin receptor 5HT3R. Vagal neurons projecting to the pancreas terminate in the commissural nucleus of the solitary tract. These neurons respond to chemical but not mechanical stimulation of the pancreas. By recording activity from nodose neurons in vivo and from sensory axons in living pancreas slices, we show that sensory nerves respond to serotonin secreted from stimulated beta cells. Serotonin is co-released with insulin and therefore conveys information about the secretory state of beta cells via vagal afferent nerves. Our study thus establishes that pancreatic islets communicate with the brain using the neural route and identifies serotonin signaling as a peripheral transduction mechanism.

neuroscience↗