Search Results (24)

A five-month-old female mixed-breed dog presented with a two-week history of polyuria, polydipsia, and vomiting. Clinical examination revealed poor body condition, growth retardation, pale oral mucous membranes, weak pulse, and prolonged capillary refill time. Laboratory findings included neutrophilic leukocytosis with a regenerative left shift, fasting hyperglycemia, elevated fructosamine, glycated hemoglobin, and β-hydroxybutyrate concentrations, while the acid–base balance remained normal. Canine-specific pancreatic lipase and trypsin-like immunoreactivity concentrations ruled out an underlying pancreatitis or exocrine pancreatic insufficiency, respectively. Urinalysis showed glycosuria and ketonuria. Supportive care included antibiotics and regular insulin administration. Abdominal ultrasonography identified a pancreatic cavity with a thick wall and mixed echogenic fluid. Ultrasound-guided drainage was performed without complications. Cytology confirmed a pancreatic abscess with pyogranulomatous inflammation, though the culture results were negative. The dog was discharged with intermediate-acting lente insulin. Follow-up ultrasonographic evaluations at 7, 14, and 21 days and 5 months post-drainage showed no recurrence. The diabetes remained well-controlled one year post-discharge. This case report describes the successful management of a dog with juvenile diabetes mellitus complicated by a pancreatic abscess, highlighting the effectiveness of percutaneous ultrasound-guided drainage combined with medical therapy. Full article

Background: Diabetes mellitus (DM) is a common potentially life-threatening endocrine disorder in pets and humans. Since only symptomatic treatment is available, a more sustainable treatment is urgently needed. Objective: The aim of this study is to establish functional differentiated canine pancreatic β-cells that release insulin upon glucose stimulus. Methods: Pancreatic tissue was obtained from surplus material of healthy dogs (n = 4), euthanized for non-pancreatic related research. Ductal cells were isolated and expanded in dog pancreas expansion media (dpEM) and differentiated and maturated in five sequentially added pancreas differentiation media (PDMs). Gene expression was analyzed by reversed transcriptase qPCR (RT-qPCR), and insulin release was analyzed with a canine-specific ELISA. Results: Canine pancreatic ductal cells (LGR5 and SOX9 expression) were differentiated into β-cells expressing key β-cell-related genes: Pancreatic and duodenal homeobox 1 (PDX1), NK6 Homeobox 1 (NKX6.1), Glucose Transporter Type 2 (GLUT2), Proprotein convertase subtilisin/kexin type 1 (PCSK1), and low levels of insulin. Neither Glucagon (α-cells) nor LGR5 and SOX9 were expressed, and somatostatin was expressed at low levels. The differentiated cells released insulin upon glucose stimulation. Conclusion and implications: The step-by-step differentiation protocol, mimicking pancreatic organogenesis, resulted in β-cells secreting insulin levels suitable for β-cell disease modelling. It remains to be seen if stem cells from diseased animals behave similarly. Full article

In many cases, the etiopathogenesis of oral cavity diseases depends on the presence of variants in some genes. Being able to identify these variants defines the possibilities and limits of therapies. This multidisciplinary case describes several pathologies of the oral cavity in a young patient affected by type 1 diabetes. The patient presented with an impacted palatal canine. Further investigation revealed cervical root resorption of the upper right central incisor. Genetic testing was performed for interleukin, VDR receptor genes, and the evaluation of periodontopathogenic bacteria. The mutational analysis carried out for the VDR polymorphisms and the IL1A, IL1B, IL6, and IL10 polymorphisms showed the presence of pathogenetic variants. The results for bacterial load showed the presence of periodontal pathogenes. The first intervention was the intentional replantation of the incisor. The second intervention was the orthodontic recovery of the impacted canine, using light forces and a hybrid anchorage with a miniscrew. At the end of orthodontic treatment, a crack was found in the upper left first premolar, which was extracted. Throughout treatment, non-invasive periodontal interventions were performed periodically to control periodontal inflammation. This case is an example of the integration of genetic analyses into the multidisciplinary diagnostic pathway. Full article

The use of nutraceuticals, mainly phytogenics, is increasingly widespread in animal nutrition, especially in dogs. The materials typically used to provide these very diverse natural compounds come from plants, but lately algae and fungi have also been used. In animal nutrition, these compounds are applied to obtain better results in the production and stability of feed and also as biofunctional substances with benefits for animal health. Polyphenols are natural compounds from the secondary metabolism of plant matter present in animal food (e.g., seeds and nuts, fruits, vegetables, herbs/aromatic plants, spices, cereals, and vegetable oils, among others). Most of the biological effects of these compounds associated with health benefits have been attributed to their antioxidant potential because they can protect cellular elements against oxidative injury, reducing the risk of dysfunctions and diseases associated with oxidative processes. Polyphenols are constituted by multiple families of substances with wide applications in pet therapy and nutrition. In this work, we review the most relevant phytogenic polyphenols, exploring their characteristics, sources, and implications for canine health. Our focus includes the effects on gastrointestinal functions and its microbiota, as well as aspects such as obesity, diabetes, and fat metabolism. Additionally, we examine their impact on cardiovascular, neurological, and immunological systems, along with their potential anti-oncogenic role. Finally, we discuss the overall role of polyphenols in dog diets and their future implications. Full article

Cell-based therapy using insulin-producing cells (IPCs) is anticipated as an alternative treatment option to insulin injection or pancreatic islet transplantation for the treatment of diabetes mellitus in both human and veterinary medicine. Several protocols were reported for the differentiation of mesenchymal stem cells (MSCs) into IPCs; to date, glucose-responsive IPCs have only been obtained from canine adipose tissue-derived MSCs (cAD-MSCs), but not from canine bone marrow-derived MSCs (cBM-MSCs). Therefore, this study aims to generate in vitro glucose-responsive IPCs from cBM-MSCs using two differentiation protocols: a two-step protocol using trichostatin (TSA) and a three-step protocol using mercaptoethanol to induce pancreatic and duodenal homeobox gene 1 (PDX-1) expression. A single experiment was carried out for each protocol. BM-MSCs from one dog were successfully cultured and expanded. Cells exposed to the two-step protocol appeared rarely grouped to form small clusters; gene expression analysis showed a slight increase in PDX-1 and insulin expression, but no insulin protein production nor secretion in the culture medium was detected either under basal conditions or following glucose stimulation. Conversely, cells exposed to the three-step protocol under a 3D culture system formed colony-like structures; insulin gene expression was upregulated compared to undifferentiated control and IPCs colonies secreted insulin in the culture medium, although insulin secretion was not enhanced by high-glucose culture conditions. The single experiment results suggest that the three-step differentiation protocol could generate IPCs from cBM-MSCs; however, further experiments are needed to confirm these data. The ability of IPCs from cBM- MSCs to produce insulin, described here for the first time, is a preliminary interesting result. Nevertheless, the IPCs’ unresponsiveness to glucose, if confirmed, would affect its clinical application. Further studies are necessary to establish a differentiation protocol in this perspective. Full article

Human patients with type 1 diabetes mellitus (T1DM) are susceptible to several long-term complications that are related to glycemic control and immune dysregulation. Immune function remains relatively unexplored in dogs with naturally occurring diabetes mellitus (NODM). Calcitriol improves various aspects of immune function in a variety of species, but its effect in diabetic dogs remains unexplored. Therefore, the objectives of this study were to (i) evaluate immune function in dogs with NODM and determine if differences exist based on the level of clinical control and (ii) assess the immunomodulatory effects of calcitriol. Twenty diabetic dogs (clinically controlled, n = ten, not controlled, n = ten) and 20 non-diabetic, healthy control dogs were included in this prospective, case–control study. Whole blood was incubated with calcitriol (10⁻⁷ M) or negative control, after which the samples were divided for phagocytosis and leukocyte cytokine response experiments. The phagocytosis of opsonized Escherichia coli (E. coli) was evaluated with flow cytometry. The samples for leukocyte cytokine response evaluations were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or phosphate buffer solution (PBS; negative control), and tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 were measured in supernatant using a canine-specific multiplex bead-based assay. The leukocytes from diabetic dogs produced higher concentrations of IL-10 (p = 0.01), IL-6 (p < 0.0001), and IL-8 (p < 0.0001) than the control dogs while controlling for the intervention and stimulant. Calcitriol decreased the supernatant concentrations of TNF-α (p < 0.001) and IL-8 (p = 0.04) with concomitant increases in IL-6 (p = 0.005). Diabetic dogs had a lower percentage of leukocytes undergoing phagocytosis (p < 0.0001) but a higher number of bacteria phagocytized per cell (p = 0.001) when compared to the control dogs. Calcitriol had no effect on phagocytic capacity. Lastly, the status of clinical control in diabetic dogs did not yield differences in immune function. These results support that dogs with NODM exhibit immune dysregulation and warrant additional investigation. Full article

Rice (Oryza sativa L.) is one of the primary sources of energy and nutrients needed by the body, and rice resistant starch (RRS) has been found to have hypoglycemic effects. However, its biological activity and specific mechanisms still need to be further elucidated. In the present study, 52 RRS differential metabolites were obtained from mouse liver, rat serum, canine feces, and human urine, and 246 potential targets were identified through a literature review and database analysis. A total of 151 common targets were identified by intersecting them with the targets of type 2 diabetes mellitus (T2DM). After network pharmacology analysis, 11 core metabolites were identified, including linolenic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, lithocholic acid, lithocholylglycine, glycoursodeoxycholic acid, phenylalanine, norepinephrine, cholic acid, and L-glutamic acid, and 16 core targets were identified, including MAPK3, MAPK1, EGFR, ESR1, PRKCA, FYN, LCK, DLG4, ITGB1, IL6, PTPN11, RARA, NR3C1, PTPN6, PPARA, and ITGAV. The core pathways included the neuroactive ligand–receptor interaction, cancer, and arachidonic acid metabolism pathways. The molecular docking results showed that bile acids such as glycoursodeoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, lithocholic acid, deoxycholic acid, and cholic acid exhibited strong docking effects with EGFR, ITGAV, ITGB1, MAPK3, NR3C1, α-glucosidase, and α-amylase. In vitro hypoglycemic experiments further suggested that bile acids showed significant inhibitory effects on α-glucosidase and α-amylase, with CDCA and UDCA having the most prominent inhibitory effect. In summary, this study reveals a possible hypoglycemic pathway of RRS metabolites and provides new research perspectives to further explore the therapeutic mechanism of bile acids in T2DM. Full article

For over 150 years, researchers have studied the (patho)physiology of the endocrine pancreas and devised treatment options for diabetes mellitus (DM). However, no cure has been developed so far. In dogs, diabetes mellitus type 1 (T1DM) is the most common presentation. Treatment consists of twice daily insulin injections, monitored by spatial blood glucose measurements. Even though dogs were instrumental in the discovery of insulin and islet transplantations, the treatment in diabetic dogs has remained unchanged for decades. Providing twice daily insulin injections is demanding for both owners and dogs and may result in hypoglycaemic events, creating the need for new treatment strategies. Novel regenerative medicine-based tools, such as improved β-cell culture protocols and artificial devices, have sparked hope for a cure. In human medicine, emerging technologies such as the transplantation of insulin-producing β-cells, generated by stem cell differentiation, with or without an encapsulation device, are currently tested in phase I/II clinical trials. As the pathogenesis of T1DM is remarkably similar between humans and dogs, novel treatment methods could be implemented in canine medicine. This review briefly summarises the physiology of the canine endocrine pancreas and the pathophysiology of canine DM before exploring current and possible future treatment options for canine DM. Full article

Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. This narrative review aims to provide relevant detailed information on (1) the canine estrus cycle and its impact on canine diabetes mellitus (CDM) etiology and management, (2) the role of pyometra as a further cause of insulin resistance, and (3) useful individual therapeutic and preventive strategies. PRDM is recognized due to diestrus, exogenous progestogen exposure, pregnancy, and P4-production ovarian dysfunction. Pyometra represents additional inflammatory and septic negative influence on insulin sensitivity, and its diagnosis associated with CDM is therapeutically challenging. The estrus cycle’s hormone fluctuations seem to modulate peripheric insulin sensibility by influencing insulin receptor (IR) affinity and its binding capacity, as well as modulating tyrosine kinase activity. Pyometra was shown to negatively influence IR compensatory mechanisms to insulin resistance causing glucose intolerance. Spaying and pregnancy termination may cause diabetes remission in PRDM cases in a median time of 10 days (1–51). Pharmacological annulment of progesterone effects may benefit patients unable to undergo surgery; however, remission chances are virtually null. The ALIVE (Agreeing Language in Veterinary Endocrinology) project proposed new criteria for CDM diagnoses and subclinical diabetes recognition. These new concepts may increase the frequency of a PRDM diagnosis and, even more, its relevance. Spaying represents a preventive measure against pyometra and PRDM that should be individually assessed in light of its recognized benefits and harms. Full article

With a close pathogenetic resemblance to human diabetes, canine Diabetes Mellitus, a chronic metabolic disease featuring abnormally high blood sugar levels, is increasing in prevalence worldwide. Unlike humans, canine glycemic control requires life-long insulin injections and dietary control in most cases, thereby jeopardizing diabetic dogs’ quality of life and increasing the difficulty of disease control. While many research studies have focused on elucidating the relationship between the canine gut microbiome and diseases, there is currently no research on the subject of diabetes mellitus in dogs. We hypothesized that the gut microbiome of canines with diabetes mellitus is different from that of healthy controls. Thus, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profiles of 16 diabetic dogs with those of 32 healthy dogs. Clostridioides difficile, Phocaeicola plebeius, Lacrimispora indolis, and Butyricicoccus pullicaecorum were found to be enriched in diabetic dogs. A distinct shift towards carbohydrate degradation metabolic pathways was found to be differentially abundant in the diabetic subjects. Alteration of the co-occurrence network was also evident in the diabetic group. In conclusion, our study suggests that the gut microbial landscape differs in diabetic canines at the genera, species, functional, and network levels. These findings have significant implications for disease management, and thus warrant further research. Full article

Sex hormones play an important role in the regulation of water homeostasis, and we have previously shown that tamoxifen (TAM), a selective estrogen receptor modulator (SERM), affects the regulation of aquaporin (AQP)-2. In this study, we investigated the effect of TAM on the expression and localization of AQP3 in collecting ducts using various animal, tissue, and cell models. The impact of TAM on AQP3 regulation was studied in rats subjected to 7 days of unilateral ureteral obstruction (UUO), with the rats fed a lithium-containing diet to induce nephrogenic diabetes insipidus (NDI), as well as in human precision-cut kidney slices (PCKS). Moreover, intracellular trafficking of AQP3 after TAM treatment was investigated in Madin-Darby Canine Kidney (MDCK) cells stably expressing AQP3. In all models, the expression of AQP3 was evaluated by Western blotting, immunohistochemistry and qPCR. TAM administration attenuated UUO-induced downregulation of AQP3 and affected the localization of AQP3 in both the UUO model and the lithium-induced NDI model. In parallel, TAM also affected the expression profile of other basolateral proteins, including AQP4 and Na/K-ATPase. In addition, TGF-β and TGF-β+TAM treatment affected the localization of AQP3 in stably transfected MDCK cells, and TAM partly attenuated the reduced AQP3 expression in TGF-β exposed human tissue slices. These findings suggest that TAM attenuates the downregulation of AQP3 in a UUO model and a lithium-induced NDI model and affects the intracellular localization in the collecting ducts. Full article

Diabetes mellitus and pancreatitis are common pancreatic diseases in dogs, affecting the endocrine and exocrine portions of the organ. Dogs have a significant role in the history of research related to genetic diseases, being considered potential models for the study of human diseases. This review discusses the importance of using the extracellular matrix of the canine pancreas as a model for the study of diabetes mellitus and pancreatitis, in addition to focusing on the importance of using extracellular matrix in new regenerative techniques, such as decellularization and recellularization. Unlike humans, rabbits, mice, and pigs, there are no reports in the literature characterizing the healthy pancreatic extracellular matrix in dogs, in addition to the absence of studies related to matrix components that are involved in triggering diabetes melittus and pancreatitis. The extracellular matrix plays the role of physical support for the cells and allows the regulation of various cellular processes. In this context, it has already been demonstrated that physiologic and pathologic pancreatic changes lead to ECM remodeling, highlighting the importance of an in-depth study of the changes associated with pancreatic diseases. Full article

The interest in stem cell research continuously increased over the last decades, becoming one of the most important trends in the 21st century medicine. Stem cell-based therapies have a potential to become a solution for a range of currently untreatable diseases, such as spinal cord injuries, type I diabetes, Parkinson’s disease, heart disease, stroke, and osteoarthritis. Hence, this study, based on canine material, aims to investigate the molecular basis of adipose-derived stem cell (ASC) differentiation into chondrocytes, to serve as a transcriptomic reference for further research aiming to introduce ASC into treatment of bone and cartilage related diseases, such as osteoarthritis in veterinary medicine. Adipose tissue samples were harvested from a canine specimen subjected to a routine ovariohysterecromy procedure at an associated veterinary clinic. The material was treated for ASC isolation and chondrogenic differentiation. RNA samples were isolated at day 1 of culture, day 30 of culture in unsupplemented culture media, and day 30 of culture in chondrogenic differentiation media. The resulting RNA was analyzed using RNAseq assays, with the results validated by RT-qPCR. Between differentiated chondrocytes, early and late cultures, most up- and down-regulated genes in each comparison were selected for further analysis., there are several genes (e.g., MMP12, MPEG1, CHI3L1, and CD36) that could be identified as new markers of chondrogenesis and the influence of long-term culture conditions on ASCs. The results of the study prove the usefulness of the in vitro culture model, providing further molecular insight into the processes associated with ASC culture and differentiation. Furthermore, the knowledge obtained could be used as a molecular reference for future in vivo and clinical studies. Full article

Accumulating data show the involvement of intestinal microbiota in the development and maintenance of numerous diseases. Many environmental factors influence the composition and function of the gut microbiota. An animal model subjected to the same environmental constraints that will allow better characterization of the microbiota–host dialogue is awaited. The domestic dog has physiological, dietary and pathological characteristics similar to those of humans and shares the domestic environment and lifestyle of its owner. This review exposes how the domestication of dogs has brought them closer to humans based on their intrinsic and extrinsic similarities which were discerned through examining and comparing the current knowledge and data on the intestinal microbiota of humans and canines in the context of several spontaneous pathologies, including inflammatory bowel disease, obesity and diabetes mellitus. Full article

The novel Eversense XL continuous glucose monitoring system (Senseonics, Inc., Germantown, Maryland) has recently been developed for monitoring diabetes in humans. The sensor is fully implanted and has a functional life of up to 180 days. The present study describes the use of Eversense XL in three diabetic dogs (DD) with good glycemic control managed by motivated owners. The insertion and use of the device were straightforward and well tolerated by the dogs. During the wearing period, some device-related drawbacks, such as sensor dislocation and daily calibrations, were reported. A good correlation between the glucose values measured by the Eversense XL and those obtained with two commercially available devices, previously validated for use in DD, was found (r_s = 0.85 and r_s = 0.81, respectively). The life of the sensor was 180 days in two of the DD and provided high satisfaction. This innovative device might be considered a future alternative for home glucose monitoring in DD. Full article