A pinboard by
Victor Ukwenya

Senior Lecturer, Federal University of Technology, Akure


Stimulatory efects of Chromolaena odorata and Tithonia diversifolia on blood production

Chromolaena odorata and Tithonia diversifolia have been combined as folkloric treatment for pediatric anemia. However, the underlying molecular mechanism of this pharmacology has not been established. This study sought to establish the effects of these plants on erythropoietin (kidney), and erythropoietin receptor (bone marrow) expression. The combination of C. odorata and T. diversifolia indeed stimulate erythropoietin expression but not via erythropoietin receptor agonism.


Different physiological roles of insulin receptors in mediating nutrient metabolism in zebrafish.

Abstract: Insulin, the most potent anabolic hormone, is critical for somatic growth and metabolism in vertebrates. Type 2 diabetes, which is the primary cause of hyperglycemia, results from an inability of insulin to signal glycolysis and gluconeogenesis. Our previous study showed that double knockout of insulin receptor a (insra) and b (insrb) caused β-cell hyperplasia and lethality from 5 dpf to 16 dpf. In this study, we characterized the physiological roles of Insra and Insrb, in somatic growth and fueling metabolism, respectively. A high-carbohydrate diet was provided for insulin receptor knockout zebrafish from 60 dpf to 120 dpf to investigate phenotype inducement and amplification. We observed hyperglycemia in both insra-/- fish and insrb-/- fish. Impaired growth hormone signaling, increased visceral adiposity, and fatty liver were detected in insrb-/- fish, which are phenotypes similar to the lipodystrophy observed in mammals. More importantly, significantly diminished protein levels of P-PPARα, P-STAT5 and IGF-1 were also observed in insrb-/- fish. In insra-/- fish, we observed increased protein content and decreased lipid content of the whole body. Taken together, although Insra and Insrb show overlapping roles in mediating glucose metabolism through the insulin signaling pathway, Insrb is more prone to promoting lipid catabolism and protein synthesis through activation of the GH signaling pathway, whereas Insra primarily acts to promote lipid synthesis via glucose utilization.

Pub.: 20 Jan '18, Pinned: 11 May '18

Studying Diabetes Through the Eyes of a Fish: Microdissection, Visualization, and Analysis of the Adult tg(fli:EGFP) Zebrafish Retinal Vasculature.

Abstract: Diabetic retinopathy is the leading cause of blindness among middle-aged adults. The rising prevalence of diabetes worldwide will make the prevention of diabetic microvascular complications one of the key research fields of the next decades. Specialized, targeted therapy and novel therapeutic drugs are needed to manage the increasing number of patients at risk of vision-loss. The zebrafish is an established animal model for developmental research questions with increasing relevance for modeling metabolic multifactorial disease processes. The advantages of the species allow for optimal visualization and high throughput drug screening approaches, combined with the strong ability to knock out genes of interest. Here, we describe a protocol which will allow easy analysis of the adult tg(fli:EGFP) zebrafish retinal vasculature as a fast read-out in settings of long-term vascular pathologies linked to neoangiogenesis or vessel damage. This is achieved via dissection of the zebrafish retina and whole-mounting of the tissue. Visualization of the exposed vessels is then achieved via confocal microscopy of the green EGFP reporter expressed in the adult retinal vasculature. Correct handling of the tissue will lead to better outcomes and less internal vessel breakage to assure the visualization of the unaltered vascular structure. The method can be utilized in zebrafish models of retinal vasculopathy linked to changes in the vessel architecture as well as neoangiogenesis.

Pub.: 25 Jan '18, Pinned: 11 May '18

A comparative genomics study of carbohydrate/glucose metabolic genes: from fish to mammals.

Abstract: Glucose plays a key role as an energy source in most mammals, but its importance in fish appears to be limited that so far seemed to belong to diabetic humans only. Several laboratories worldwide have made important efforts in order to better understand this strange phenotype observed in fish. However, the mechanism of carbohydrate/glucose metabolism is astonishingly complex. Why basal glycaemia is different between fish and mammals and how carbohydrate metabolism is different amongst organisms is largely uncharted territory. The utilization of comparative systems biology with model vertebrates to explore fish metabolism has become an essential approach to unravelling hidden in vivo mechanisms. In this study, we first built a database containing 791, 593, 523, 666 and 698 carbohydrate/glucose metabolic genes from the genomes of Danio rerio, Xenopus tropicalis, Gallus gallus, Mus musculus and Homo sapiens, respectively, and most of these genes in our database are predicted to encode specific enzymes that play roles in defined reactions; over 57% of these genes are related to human type 2 diabetes. Then, we systematically compared these genes and found that more than 70% of the carbohydrate/glucose metabolic genes are conserved in the five species. Interestingly, there are 4 zebrafish-specific genes (si:ch211-167b20.8, CABZ01043017.1, socs9 and eif4e1c) and 1 human-specific gene (CALML6) that may alter glucose utilization in their corresponding species. Interestingly, these 5 genes are all carbohydrate regulation factors, but the enzymes themselves are involved in insulin regulation pathways. Lastly, in order to facilitate the use of our data sets, we constructed a glucose metabolism database platform ( ). This study provides the first systematic genomic insights into carbohydrate/glucose metabolism. After exhaustive analysis, we found that most metabolic genes are conserved in vertebrates. This work may resolve some of the complexities of carbohydrate/glucose metabolic heterogeneity amongst different vertebrates and may provide a reference for the treatment of diabetes and for applications in the aquaculture industry.

Pub.: 13 Apr '18, Pinned: 11 May '18

Panax ginseng (Korea Red Ginseng) repairs diabetic sensorineural damage through promotion of the nerve growth factor pathway in diabetic zebrafish

Abstract: Publication date: Available online 16 February 2018 Source:Journal of Ginseng Research Author(s): Youn Hee Nam, Hyo Won Moon, Yeong Ro Lee, Eun Young Kim, Isabel Rodriguez, Seo Yule Jeong, Rodrigo Castañeda, Ji-Ho Park, Se-Young Choung, Bin Na Hong, Tong Ho Kang Background Diabetic sensorineural damage is a complication of the sensory neural system, resulting from long-term hyperglycemia. Red ginseng (RG) has shown efficacy for treatment of various diseases, including diabetes mellitus; however, there is little research about its benefit for treating sensorineural damage. Therefore, we aim to evaluate RG efficacy in alloxan-induced diabetic neuromast (AIDN) zebrafish. Methods In this study, we developed and validated an AIDN zebrafish model. To assess RG effectiveness, we observed morphological changes in live neuromast zebrafish. Also, zebrafish has been observed to have an ultrastructure of hair-cell cilia under scanning electron microscopy. Thus, we recorded these physiological traits to assess hair cell function. Finally, we confirmed that RG promoted neuromast recovery via nerve growth factor signaling pathway markers. Results First, we established an AIDN zebrafish model. Using this model, we showed via live neuromast imaging that RG fostered recovery of sensorineural damage. Damaged hair cell cilia were recovered in AIDN zebrafish. Furthermore, RG rescued damaged hair cell function through cell membrane ion balance. Conclusion Our data suggest that RG potentially facilitates recovery in AIDN zebrafish, and its mechanism seems to be promotion of the nerve growth factor pathway through increased expression of topomyosin receptor kinase A, transient receptor potential channel vanilloid subfamily type 1, and mitogen-activated protein kinase phosphorylation.

Pub.: 15 Apr '18, Pinned: 11 May '18

Hyperglycemia elicits anxiety-like behaviors in zebrafish: Protective role of dietary diphenyl diselenide.

Abstract: Diabetes mellitus (DM) is a chronic metabolic disease that may comorbid with various psychiatric disorders, such as anxiety and depression. The search for effective therapeutics to alleviate hyperglycemia and complications resulting from DM is continuous. Here we investigate the effects of diphenyl diselenide (DD), an organoselenium compound with several pharmacological properties, in a zebrafish model of hyperglycemia. Fish were fed for 74 days with a diet containing 3 mg/Kg DD, a concentration chosen after experiments based in a dose-response curve (DD 1, 2 and 3 mg/Kg) that did not cause overt toxicity (mortality, weight loss and neurobehavioral deficits). In the last 14 days of the experimental period, fish were concomitantly exposed to a glucose solution (111 mM). Afterwards, blood glucose levels, brain selenium (Se) content, and behavioral analysis aiming to assess anxiety-like behaviors and locomotor/exploratory activities were performed. In the novel tank diving test, glucose decreased vertical exploration and fish spent less time in the lit area when tested in the light-dark test, suggesting increased anxiety-like behavior. Moreover, DD decreased blood glucose levels in hyperglycemic fish as well as prevented the development of anxiety-related symptoms. DD diet alone did not change glycemia and behavioral parameters, but increased Se levels in the brain without affecting the cellular viability. Collectively, our findings highlight the growing utility of this zebrafish hyperglycemia model as a valuable strategy for further research in DM field and neuroprotective approaches. Copyright © 2018. Published by Elsevier Inc.

Pub.: 04 May '18, Pinned: 11 May '18