Biology subjects

Caicedo, A.

Publications and source records attributed to Caicedo, A..

7 recordsLinked to original sources

bioRxiv2025

A neural entero-pancreatic pathway that regulatesinsulin secretion and glucose tolerance

Signals from the gut enhance pancreatic secretion of insulin and thus influence glucose metabolism. This phenomenon, known as the incretin effect, is thought to be mediated by hormones secreted from enteroendocrine cells. The endocrine model, however, does not fully capture the complexity of gut-pancreas interactions. Anatomical studies identified a direct neural connection between the gut and the pancreas, known as the entero-pancreatic plexus. The role of this connection in regulating glucose metabolism remains unknown. Here we identify and functionally characterize a subpopulation of nitridergic myenteric neurons in the proximal duodenum that project directly to the pancreas. The anatomical and transcriptomic signature of these neurons places them downstream of glutamatergic and enkephalinergic enteric interneurons that indirectly respond to luminal nutrient stimuli. Their axonal projections to the pancreas contact neuro-insular ganglia and reach into the islet parenchyma. When activated chemogenetically, this circuit increases Ca2+ responses in pancreatic beta cells, enhances insulin secretion, and improves glucose tolerance in vivo. Our findings reveal a direct gut-pancreas neural pathway that complements incretin signaling in potentiating insulin secretion. This unexpectedly strong neuronal modulation of beta cell function could be harnessed to improve glycemic control in diabetes.

neuroscience↗

bioRxiv2025

Mapping functional hemodynamic and metabolic responses to dementia: a broadband spectroscopy pilot study

SignificanceBroadband near-infrared spectroscopy (bNIRS) can simultaneously monitor several chromophores including the oxidative state of cytochrome c-oxidase (oxCCO), an oxygen metabolism biomarker whose activity is altered in Alzheimers disease. Being a portable and non-invasive neuromonitoring technique, bNIRS could thus provide accessibility to brain-specific biomarkers and aid in the dementia diagnostic pathway. AimWe use bNIRS recorded functional haemodynamic and oxCCO changes to assess their relevance in Alzheimers disease dementia as potential biomarkers. ApproachUsing a visual-stimulus paradigm, we recorded functional changes in oxy-, deoxy-haemoglobin and oxCCO in three similarly aged cohorts: healthy controls (n=5), individuals with mild cognitive impairment (n=7) and individuals with Alzheimers dementia (n=7). We then selected features from these functional responses to find the best correlation with clinical cognitive markers (cognitive and behavioural test scores and clinical diagnosis) using canonical correlation analysis. ResultsWe found individual variations in peak amplitude and time-to-peak for all the stimulus-evoked bNIRS signals across the three cohorts. Canonical correlation analysis showed a strong correlation between bNIRS features and the clinical cognitive markers (r=0.902). However, repeating the same analysis by excluding the bNIRS oxCCO features leads to a significantly lower correlation (r=0.687) with the clinical markers. ConclusionsoxCCO could be a crucial biomarker, partly explaining cognitive differences with dementia. bNIRS uniquely provides a portable and non-invasive technique to monitor several chromophores simultaneously including oxCCO with potential future applications in tracking dementia progression.

bioengineering↗

bioRxiv2024

Comparative tissue-specific transcriptomics reveal the genetic bases underlying evolutionary convergence of seed shattering in two independently evolved weedy rice lineages

The repeated evolution of high seed shattering during multiple independent de-domestications of cultivated Asian rice (Oryza sativa) into weedy rice is a prime example of convergent evolution. Weedy rice populations converge in histological features of the abscission zone (AZ), a crucial structure for seed abscission, while ancestral cultivated rice populations exhibit varied AZ morphology and levels of shattering. However, the genetic bases of these phenotypic patterns remain unclear. We examined the expression profiles of the AZ region and its surrounding tissues at three developmental stages in two low-shattering cultivars of aus and temperate japonica domesticated varieties and in two genotypes of their derived high-shattering weed groups, Blackhull Awned (BHA) and Spanish Weedy Rice (SWR), respectively. Consistent with the greater alteration of AZ morphology during the de-domestication of SWR than BHA, fewer genes exhibited a comparable AZ-region exclusive expression pattern between weed and crop in the japonica lineage than in aus lineage. Transcription factors related to the repression of lignin and secondary cell deposition, such as, OsWRKY102 and OsXND-1-like, along with certain known shattering genes involved in AZ formation, likely played a role in maintaining AZ region identity in both lineages. Meanwhile, most genes exhibiting AZ-region exclusive expression patterns do not overlap between the two lineages and the genes exhibiting differential expression in the AZ region between weed and crop across the two lineages are enriched for different gene ontology terms. Our findings suggest genetic flexibility in shaping AZ morphology, while genetic constraints on AZ identity determination in these two lineages. Significance statementExploring the extent of genetic convergence that underlies the morphological convergence - specifically, the recurrent evolution of complete abscission zones in independently evolved weedy rice populations originating from different cultivated rice populations with varying degrees of disrupted abscission zones - can improve our understanding not only of the genetic mechanisms behind convergent evolution, but also of the genetics underlying the agriculturally importance trait of seed shattering.

plant biology↗

bioRxiv2021

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↗

bioRxiv2021

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↗

bioRxiv2021

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↗

bioRxiv2019

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↗