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Taurine is a sulfated amino acid derivative that plays an important role in maintaining the cell function of the living body. Although taurine has been shown to ameliorate diabetes, its mechanism of action has not yet been fully elucidated. The present study investigated the effects of taurine on diabetes focusing on glucose metabolism and oxidative stress. Type 1 diabetes was induced by the administration of streptozotocin (STZ) to male C57BL/6J mice. Taurine was dissolved in drinking water at 3% (w/v) and allowed to be freely ingested by diabetic mice. The weight and blood glucose levels were measured weekly. After nine weeks, mice were sacrificed and their serum, liver, and kidney were removed and used for biochemical and histological analyses. A microarray analysis was also performed in normal mice. Taurine alleviated STZ-induced hyperglycemia and hyperketonemia, accompanied by the suppression of the decrease in hepatic glycogen and upregulation of the mRNA expression of hepatic glucose transporter GLUT-2. Furthermore, STZ-induced elevation of oxidative stress in the liver and kidney was suppressed by taurine treatment. These results showed that taurine ameliorated diabetes and diabetic complications by improving hepatic glucose metabolism and reducing oxidative stress.

This study was conducted to evaluate the influence of acute exercise on insulin secretion capacity and its underlying regulatory mechanisms in isolated pancreatic islets. Two groups of male C57BL/6J mice were assessed: a sedentary control group and a group that was subjected to a single 3-h (hour) period of swimming exercise. Immediately after the swimming exercise, an oral glucose tolerance test (OGTT) was performed and glucose-stimulated insulin secretion was assessed in isolated islets. The expression levels of proteins involved with insulin secretion were also examined in isolated islets. The areas under the curves (AUCs) for plasma insulin in the OGTT did not differ significantly between the control and exercise groups. However, the exercise group exhibited a significantly higher insulin secretion capacity of isolated islets relative to the control group (p < 0.05). Glucose transporter (GLUT)-2 protein, which is the predominant glucose transporter isoform in rodent pancreatic β cells, was expressed at a higher level in the exercise group relative to the control group (p = 0.05), but the expression of other proteins (i.e., markers of autophagy and intracellular Ca2+) were unchanged. These results indicate that the increased insulin secretion capacity following acute exercise is accompanied by increased GLUT-2 protein content.

Obesity and diabetes, often characterized as “metabolic syndrome”, have been recognized as two of the most important public health issues worldwide. The objective of the present research was to evaluate green and yellow papaya for anti-oxidation and anti-diabetic properties. Leaves, skin, pulp, and seed samples from papayas were freeze-dried and then extracted in water or 80% methanol. The extracts were used to determine total polyphenolic content and anti-oxidation activities, and to determine biological activities, including glucose uptake, Glut-2 expression, triglyceride reduction, and wound-healing activity. Our data demonstrated that methanol and water extracts of green and yellow papaya have similar concentrations of polyphenols in skin (10–20 mg/g dry powder), leaf (25–30 mg/g dry powder), and pulp (1–3 mg/g dry powder) fractions. However, both methanol and water extracts of seeds from yellow papaya have substantially higher concentrations of polyphenols compared to green papaya. Both water and methanol extracts of yellow papaya exhibited higher anti-oxidation activity compared to green papaya in skin (50–60%), pulp (200–300%), and seeds (10–800%). Old leaves also showed greater anti-oxidation activity (30–40%) compared to new leaves. Pulp extracts from both yellow and green papaya stimulated greater glucose uptake, but only pulp from green papaya stimulated glucose uptake in muscle cells. Similarly, pulp extract stimulated glucose transporter Glut-2 expression in liver cells. The skin, pulp, and seeds of green or yellow papaya showed triglyceride-lowering activity in liver cells by 60–80%, but samples taken from yellow papaya had a more potent effect. Seeds from both green and yellow papaya significantly stimulated the migration of fibroblasts in the wounded area by 2–2.5-fold compared to the untreated control. Consistent with these data, seeds from both green and yellow papaya also significantly stimulated collagen synthesis in fibroblast cells by almost 3-fold. In conclusion, our data indicate that different parts of papaya produce stimulatory effects on glucose uptake, Glut-2 expression, TG reduction, and wound-healing activities. This study concludes that different parts of the papaya can be beneficial for preventing diabetes and diabetes-related wound healing.

Context: Gongronema latifolium Benth (Asclepiadaceae) has been highly utilized in controlling diabetes mellitus traditionally in the eastern part of Nigeria. Objectives: Antihyperglycaemic and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats. Materials and methods: Forty-eight female Wistar rats were induced intraperitoneally using alloxan (150 mg/kg body weight). The rats were separated into six groups (n = 8) as follows: non-diabetic control, diabetic control, diabetic rats administered 5 mg/kg body weight of metformin, and diabetic rats administered 6.36, 12.72 and 25.44 mg/kg body weight (ethnobotanical doses) of G. latifolium orally daily. On the 14th day, the animals were sacrificed and different antihyperglycaemic parameters were evaluated as well as its related gene expressions. Results: Diabetic rats administered three doses of aqueous extract of G. latifolium significantly (p

Objective: The aim of this study was to investigate the effect of 12 weeks aerobic training on PDX-1 and GLUT2 gene expression in the pancreatic tissue of type 2 diabetic rats. Materials and Methods: 21 wistar male rats were placed in 3 groups (healthy, diabetic, aerobic diabetic). Diabetes was induced by peritoneum injection of nicotine amid. Training program lasted 12 weeks, five sessions per week by gradual increase of speed (18 to 26 meters on minutes) and time (10 to 55 minutes) in the form of running on the treadmill. After 12 week aerobic training, PDX-1 and GLUT-2 genes were measured. Data was analyzed using ANOVA with 5 % significance level. Results: Aerobic training caused a significant increase in the expression of GLUT2 (P-value: 0.043) and PDX-1 genes (P-value: 0.007) in the pancreatic tissue of rats with type 2 diabetes (p value: 0.05). Also aerobic training had a significant effect on serum glucose (P-value: 0.001) and insulin levels (P-value: 0.001). Conclusion: It is concluded that aerobic training has significant effects on diabetic control by increasing the expression of PDX1 and GLUT-2 which lowers serum glucose.

This study aimed to analyze the ameliorative effect of Crataegus aronia against type 2 diabetes mellitus (type 2-DM). Type 2-DM rats were treated with the extract and the changes in serum parameters (glucose, insulin, HbA 1c and lipids) and hepatic parameters (oxidative stress, inflammation and mRNA levels of GLUT-2 and gluconeogenesis enzymes) were compared to those of control and untreated type 2-DM rats. Also, levels of hepatic insulin receptors 1A (IR-1A) were measured immunohistochemically and compared between groups. In type 2-DM rats, C. aronia significantly improved the oral glucose tolerance test (OGTT), lowered plasma glucose, serum lipid levels and the hepatic glycogen content. Also, it significantly lowered the levels of hepatic lipid peroxidation, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) and enhanced the level of reduced glutathione (GSH) and increased superoxide dismutase (SOD) activity. C. aronia enhanced hepatic mRNA expression of the insulin receptor A isoform (IR-A) and glucose 6-phosphatase (G6Pase), and lowered glucose transporter-2 (GLUT-2) and glycerol kinase (GK) mRNA expression. In conclusion, C. aronia ameliorates T2DM by inhibiting hepatic glucose output. https://doi.org/10.2298/ABS170510044M Received: May 10, 2017; Revised: July 23, 2017; Accepted: September 18, 2017; Published online: November 13, 2017 How to cite this article: Mostafa DG, Khaleel EF, Abdel-Aleem GA. Inhibition of the hepatic glucose output is responsible for the hypoglycemic effect of Crataegus aronia against type 2 diabetes mellitus in rats. Arch Biol Sci. 2018;70(2):277-87.

The knowledge about transport of sugars in animals and birds gastrointestinal tract is very important for science as carbohydrates are the main energy source of food. Since until now there is few information about the localization of glucose transporters - integral membrane proteins that mediate the transport of glucose and related substances across the cellular membranes - in birds gastrointestinal tract, the aim of the present study was to localize glucose transporters-2 and -5 (GLUT-2 and -5) in three parts of the ostriches gastrointestinal tract – proventriculus, duodenum and ileum - comparatively in ostrich chicken in their early ontogenesis period. Material from the superficial gland zone of the proventriculus, duodenum and terminal zone of the ileum were collected from eight female ostriches (Struthio camelus var. Domesticus): two chickens after hatching, three 7 and three 30-days old ostriches. The material was fixed with 10% formalin, embedded into paraffin, slices 7 μm thick were cut followed by immunohistochemical staining with polyclonal primary antibodies Rabbit anti-GLUT-2 and Rabbit anti-GLUT-5, carried out according to the manufacturers guidelines (IHC kit, Abcam, UK). The results showed that the staining for both antibodies was weaker in all parts of the gastrointestinal tract of ostriches after hatching compared to 7 and 30 days old ostriches showing that the gastrointestinal tract of ostriches immediately after hatching is not entirely capable of transportation of carbohydrates. The results of our study may indicate the possibility of a close relationship between feeding and the ability to transport sugars in the gastrointestinal tract.

Background: A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, testosterone acts via androgen receptors (AR) to increase insulin receptor (IR) expression and glycogen synthesis, and to decrease glucose uptake controlled by liver-specific glucose transporter 2 (GLUT-2). Our previous study indicated that this mechanism may be impaired by finasteride, a popular drug used in urology and dermatology, inhibiting 5&alpha, reductase 2, which converts testosterone (T) into dihydrotestosterone (DHT). Our research has also shown that the offspring of rats exposed to finasteride have an altered T&ndash, DHT ratio and show changes in their testes and epididymides. Therefore, the goal of this study was to assess whether the administration of finasteride had an trans-generational effect on (i) GLUT-2 dependent accumulation of glycogen in the liver, (ii) IR and AR expression in the hepatocytes of male rat offspring, (iii) a relation between serum T and DHT levels and the expression of GLUT2, IR, and AR mRNAs, (iv) a serum glucose level and it correlation with GLUT-2 mRNA. Methods: The study was conducted on the liver (an androgen-dependent organ) from 7, 14, 21, 28, and 90-day old Wistar male rats (F1:Fin) born by females fertilized by finasteride-treated rats. The control group was the offspring (F1:Control) of untreated Wistar parents. In the histological sections of liver the Periodic Acid Schiff (PAS) staining (to visualize glycogen) and IHC (to detect GLUT-2, IR, and AR) were performed. The liver homogenates were used in qRT-PCR to assess GLUT2, IR, and AR mRNA expression. The percentage of PAS-positive glycogen areas were correlated with the immunoexpression of GLUT-2, serum levels of T and DHT were correlated with GLUT-2, IR, and AR transcript levels, and serum glucose concentration was correlated with the age of animals and with the GLUT-2 mRNA by Spearman&rsquo, s rank correlation coefficients. Results: In each age group of F1:Fin rats, the accumulation of glycogen was elevated but did not correlate with changes in GLUT-2 expression. The levels of GLUT-2, IR, and AR transcripts and their immunoreactivity statistically significantly decreased in F1:Fin animals. In F1:Fin rats the serum levels of T and DHT negatively correlated with androgen receptor mRNA. The animals from F1:Fin group have statistically elevated level of glucose. Additionally, in adult F1:Fin rats, steatosis was observed in the liver (see Appendix A). Conclusions: It seems that treating male adult rats with finasteride causes changes in the carbohydrate metabolism in the liver of their offspring. This can lead to improper hepatic energy homeostasis or even hyperglycaemia, insulin resistance, as well as some symptoms of metabolic syndrome and liver steatosis.

Fanconi- Bickel Syndrome (FBS) is a rare glycogen storage disease (GSD) . Transient diabetes is rarely reported with FBS. We describe a patient with FBS diagnosed by diabetes findings and identification of a mutation in the GLUT2. A male infant, from a consanguineous marriage, presented with hyperglycemia and urinary system infections at 59 days and was given insulin therapy. At age 3 months, insulin was discontinued. Neonatal diabetes may be a first presentation of infants with FBS. [Med-Science 2017; 6(1.000): 111-3]

Backdround/Aims: The aim of this work was to study the effect and mechanism of action of leptin added apically, on glucose absorption, using Caco-2 cells as a model. Methods: Cells were grown on inserts and treated with leptin, at different time points after confluence. Radiolabelled glucose was added to the upper chamber and samples from the lower chamber were collected and assayed for radioactivity. Results: Glucose absorption increased with an increase in the level of differentiation and was associated with an increase in the protein expression level of glucose transporters. Leptin reduced glucose absorption only by day 16 after confluence, the time at which apical leptin receptors started appearing. This inhibitory effect became higher the longer the post confluence period, and was prominent on day 23. The hormone effect was found to be mediated via a decrease in the number of glucose transporters (SGLT1 and GLUT2) and a decrease in the activity of the Na+/K+ ATPase which was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of enzyme activators. Conclusion: It was concluded that by day 23 post confluence, Caco-2 cells are differentiated and are appropriate to use as a model for intestinal transport studies.

Lycium barbarum L. polysaccharide (LBP) is prepared from Lycium barbarum L. (L. barbarum), which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1. LPB decreased the absorption of glucose in Caco2 cell, and down-regulated the expression of SGLT-1. These results suggest that LBP might be transported across the human intestinal epithelium through SGLT-1 and it inhibits glucose uptake via down-regulating SGLT-1.

Objective: The aim of this study was to evaluate the effect of exendin-4 (EX-4) on differentiation of insulin-producing cells (IPCs) from rat bone marrow-derived mesenchymal stem cells (RAT-BM-MSCs). Materials and Methods: In this experimental study, RAT-BM-MSCs were cultured and the cells characterized by flow cytometry analysis of cell surface markers. RAT-BM-MSCs were subsequently treated with induction media with or without EX-4. After induction, the presence of IPCs was demonstrated with dithizone (DTZ) staining and gene expression profiles for pancreatic cell differentiation markers (PDX-1, GLUT-2, insulin) were assessed using reverse transcription polymerase chain reaction (RT-PCR). Insulin excreted from differentiated cells was analyzed with radioimmunoassay (RIA). The two-tailed student’s t-test was used for comparison of the obtained values. Results: The percentage of DTZ-positive cells significantly increased in EX-4 treated cells (p

In this study we have investigated the insulin secretory response to glucose and other secretagogues (2-ketoisocaproate, 3-isobutyl-1-methyl-xanthine and arginine) of pancreatic islets isolated from Sprague–Dawley rats of various ages (from 2 to 28 months). Our results showed a significant decline in the glucose-stimulated insulin secretion, starting at 12 months of age. On the other hand, the response to non-glucose secretagogues (and mainly to 2-ketoisocaproate) was less impaired with advancing age than that to glucose. We also observed a progressive age-related decline of protein levels of the glucose transporter GLUT-2 in pancreatic islets, which was temporally concomitant and quantitatively comparable with the β-cell alteration in glucose responsiveness (−40/50%). Finally, we observed a significant increase of the islets insulin content in older rats with respect to younger animals. We conclude that in the islet of older rats the impaired capability to respond to glucose could be dependent, at least in part, on the age-dependent reduction in GLUT-2 and could be compensated by mechanisms including a preserved responsiveness to non-glucose secretagogues and/or the development of islet hypertrophy.

Inflammatory mechanisms play a key role in the pathogenesis of type 1 and type 2 diabetes. IL6, a pleiotropic cytokine with impact on immune and non-immune cell types, has been proposed to be involved in the events causing both forms of diabetes and to play a key role in experimental insulin-dependent diabetes development. The aim of this study was to investigate how beta-cell specific overexpression of IL-6 influences diabetes development. We developed two lines of rat insulin promoter (RIP)-lymphocytic choriomeningitis virus (LCMV) mice that also co-express IL6 in their beta-cells. Expression of the viral nucleoprotein (NP), which has a predominantly intracellular localization, together with IL6 led to hyperglycemia, which was associated with a loss of GLUT-2 expression in the pancreatic beta-cells and infiltration of CD11b(+) cells, but not T cells, in the pancreas. In contrast, overexpression of the LCMV glycoprotein (GP), which can localize to the surface, with IL-6 did not lead to spontaneous diabetes, but accelerated virus-induced diabetes by increasing autoantigen-specific CD8(+) T cell responses and reducing the regulatory T cell fraction, leading to increased pancreatic infiltration by CD4(+) and CD8(+) T cells as well as CD11b(+) and CD11c(+) cells. The production of IL-6 in beta-cells acts prodiabetic, underscoring the potential benefit of targeting IL6 in diabetes.

Failures in the absorptive process of monosaccharides during the early postnatal phase at intestinal level, through SGLT-1 and GLUT-2 glucose transporters could lead to animal death. The objective of this study was to determine the hexose transporters SGLT- 1 and GLUT-2 distribution in the gut and its relation with blood glucose levels in baby alpacas. A total of 36 alpacas between 1 to 45 days of age were used. Blood glucose level was determined by enzymatic test and the presence of transporters by immunohistochemistry, using rabbit policlonal antibody anti SGLT-1 and anti GLUT-2. The intensity of the dial (0: no dial, 1; mild dial; 2: strong dial) was evaluated in the axis villus-crypt. The results showed mostly mild dial (degree 1) from the day of birth for the two transporters towards strong (degree 2) by week 2, especially at the jejunum. In addition, SGLT-1 had a greater degree of dial than GLUT-2 in all portions of the intestine at all ages. The blood glucose levels varied from 150 mg/ dL (day 1) to 176 mg / dL (week 5), with significant differences between day of birth and animals at 3 to 5 weeks of age (p, Fallas en los procesos absortivos de monosacáridos a nivel intestinal en la etapa postnatal temprana, a través de transportadores de glucosa SGLT-1 y GLUT-2, pueden conducir a la muerte del animal. El presente estudio se planteó con el objetivo de identificar la distribución de transportadores de hexosas SGLT-1 y GLUT-2 en el eje cripta-vellosidad de la mucosa del intestino y su relación con los niveles de glucemia en crías de alpacas. Se utilizaron 36 animales de 1 a 45 días de edad. La glucemia se determinó por análisis enzimático y la presencia de transportadores mediante inmunohistoquímica, para lo cual se usó anticuerpos policlonales de conejo anti SGLT- 1 y anti GLUT-2. La intensidad de la marcación (0: sin marcación; 1: marcación leve; 2: marcación fuerte) se observó en el eje cripta-vellosidad. Los resultados muestran una marcación generalmente leve (grado 1) desde el primer día de edad para los dos transportadores, tornándose fuerte (grado 2) hacia la semana 2, especialmente en la zona apical del eje a nivel de yeyuno. Además, SGLT-1 tuvo una marcación de mayor valor que GLUT-2 en todas las porciones del intestino, indistintamente de la edad. Los niveles de glucemia variaron de 150 mg/dL (día 1) a 176 mg/dL (semana 5), con diferencia significativa (p

Background: Sporadic type of Alzheimer’ s disease (sAD) is associated with brain insulin receptor (IR) signalling abnormalities. The sequence of these events in relation to the beta amyloid (Aβ ) pathology can be traced only in sAD animal model, rats treated intracerebroventricularly with streptozotocin (STZ-icv). STZ enters the cell through glucose transporter type 2 (GLUT2) and selectively damages insulin producing/secreting cells and IR, as well as GLUT2. The time course of brain insulin system dysfunction following damage induced by icv application of GLUT2- and IR-toxic drug was investigated in this sAD model. Methods: Male Wistar rats (3-4 month old, 6-8 per group) were treated bilaterally icv with STZ (1-3 mg/kg) and followed after 1, 3 and 6 months for the memory (Morris Water Maze Swimming Test), hippocampal neurochemistry (RT-PCR for insulin-1 /Ins-1/, IR and insulin degrading enzyme /IDE/, immunoblotting for IR, protein kinase B /Akt/PKB/, glycogen synthase kinase 3 /GSK-3/, IDE, tau protein, and Elisa assay for tyrosine kinase /TK/), and histology (immunohistochemistry and Congo red staining for Aβ ). Data were analysed by Kruskal Wallis median and Mann Whitney U test. Results: One month following the STZ-icv treatment IR mRNA and protein were decreased (p