scholarly journals Inhibitory Effect of Tangeretin and Cardamonin on Human Intestinal SGLT1 Activity In Vitro and Blood Glucose Levels in Mice In Vivo

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3382
Author(s):  
Hideo Satsu ◽  
Ryosuke Shibata ◽  
Hiroto Suzuki ◽  
Shimon Kimura ◽  
Makoto Shimizu

Rapid postprandial blood glucose elevation can cause lifestyle-related diseases, such as type II diabetes. The absorption of food-derived glucose is primarily mediated by sodium/glucose cotransporter 1 (SGLT1). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases. In this study, we established a CHO cell line stably expressing human SGLT1 and examined the effects of phytochemicals on SGLT1 activity. Among the 50 phytochemicals assessed, tangeretin and cardamonin inhibited SGLT1 activity. Tangeretin and cardamonin did not affect the uptake of L-leucine, L-glutamate, and glycyl-sarcosine. Tangeretin, but not cardamonin, inhibited fructose uptake, suggesting that the inhibitory effect of tangeretin was specific to the monosaccharide transporter, whereas that of cardamonin was specific to SGLT1. Kinetic analysis suggested that the suppression of SGLT1 activity by tangeretin was associated with a reduction in Vmax and an increase in Km, whereas suppression by cardamonin was associated with a reduction in Vmax and no change in Km. Oral glucose tolerance tests in mice showed that tangeretin and cardamonin significantly suppressed the rapid increase in blood glucose levels. In conclusion, tangeretin and cardamonin were shown to inhibit SGLT1 activity in vitro and lower blood glucose level in vivo.

2019 ◽  
pp. 15-22
Author(s):  
Khoa Bao Chau Thai ◽  
Huu Tien Nguyen ◽  
Huu Dung Tran

Introduction: Nowadays, resistant starches are interested as a supplement food by effecting on the limit of postprandial blood glucose increase and supporting for the diabetes treatment. Recently, we have semisynthesized the acetylated wheat starch (AWS) oriented for supporting the treatment of diabetes mellitus, which is the RS4 formed by chemical structure modification. AWS has been proved itself to show strong resistance to amylase activity in-vitro as well as to be safety in-vivo. Materials and Methods: In this study, we continued to evaluate AWS’s ability to limit postprandial blood glucose increase and determined shortchain fatty acids (SCFAs) metabolized from AWS in the gastrointestinal tract of healthy mice by HPLC. Results: the mice fed AWS exhibited a very limited increase in blood glucose levels and remained stable for 2 hours after meals comparing with the control group (mice fed natural wheat starch) (NWS). Simultaneously, the content of SCFAs produced in the caecum of the mice fed AWS was significantly higher than mice fed NWS, especially with acetic and propionic acids by 28% and 26%, respectively. Conclusion: AWS has been shown to limit postprandial hyperglycemia in mice effectively through the resistance to amylase hydrolysis in the small intestine. When going into the caecum, it is fermented to form SCFAs that provide a part of the energy for the body’s activities and to avoid rotten fermentation causing digestive disorders, which are inherent restrictions of normal high cellulose and fiber food. Key words: acetylated wheat starch, natural wheat starch, SCFA, blood glucose


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Li Yan Chan ◽  
Masaki Takahashi ◽  
Pei Jean Lim ◽  
Shinya Aoyama ◽  
Saneyuki Makino ◽  
...  

AbstractType 2 diabetes mellitus (T2DM) is a chronic disease, and dietary modification is a crucial part of disease management. Okara is a sustainable source of fibre-rich food. Most of the valorization research on okara focused more on the physical attributes instead of the possible health attributes. The fermentation of okara using microbes originated from food source, such as tea, sake, sufu and yoghurt, were explored here. The aim of this study is to investigate fermented okara as a functional food ingredient to reduce blood glucose levels. Fermented and non-fermented okara extracts were analyzed using the metabolomic approach with UHPLC-QTof-MSE. Statistical analysis demonstrated that the anthraquinones, emodin and physcion, served as potential markers and differentiated Eurotium cristatum fermented okara (ECO) over other choices of microbes. The in-vitro α-glucosidase activity assays and in-vivo mice studies showed that ECO can reduce postprandial blood glucose levels. A 20% ECO loading crispy snack prototype revealed a good nutrition composition and could serve as a fundamental formulation for future antidiabetes recipe development, strengthening the hypothesis that ECO can be used as a novel food ingredient for diabetic management.


2015 ◽  
Vol 225 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Astrid C Hauge-Evans ◽  
James Bowe ◽  
Zara J Franklin ◽  
Zoheb Hassan ◽  
Peter M Jones

The inhibitory effect of somatostatin (SST) on insulin secretionin vivois attributed to a direct effect on pancreatic beta cells, but this is inconsistent with somein vitroresults in which exogenous SST is ineffective in inhibiting secretion from isolated islets. We therefore investigated whether insulin secretion from the pancreatic islets may partly be regulated by an indirect effect of SST mediated via the CNS. Islet hormone secretion was assessedin vitroby perifusion and static incubations of isolated islets andin vivoby i.v. or i.c.v. administration of the SST analogue BIM23014C with an i.v. glucose challenge to conscious, chronically catheterised rats. Hormone content of samples was assessed by ELISA or RIA and blood glucose levels using a glucose meter. Exogenous SST14/SST28 or BIM23014C did not inhibit the release of insulin from isolated rodent isletsin vitro, whereas peripheral i.v. administration of BIM23014C (7.5 μg) with glucose (1 g/kg) led to decreased plasma insulin content (2.3±0.5 ng insulin/ml versus 4.5±0.5 ng/ml att=5 min,P<0.001) and elevated blood glucose levels compared with those of the controls (29.19±1.3 mmol/l versus 23.5±1.7 mmol/l,P<0.05). In contrast, central i.c.v. injection of BIM23014C (0.75 μg) had no significant effect on either plasma insulin (3.3±0.4 ng/ml,P>0.05) or blood glucose levels (23.5±1.7 mmol/l,P>0.05) although i.v. administration of this dose increased blood glucose concentrations (32.3±0.7 mmol/l,P<0.01). BIM23014C did not measurably alter plasma glucagon, SST, GLP1 or catecholamine levels whether injected i.v. or i.c.v. These results indicate that SST does not suppress insulin secretion by a centrally mediated effect but acts peripherally on islet cells.


2019 ◽  
Vol 20 (6) ◽  
pp. 1517 ◽  
Author(s):  
Kai Wang ◽  
Yu Su ◽  
Yuting Liang ◽  
Yanhui Song ◽  
Liping Wang

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.


mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Rebecca J. Marshall ◽  
Pornthida Armart ◽  
Katina D. Hulme ◽  
Keng Yih Chew ◽  
Alexandra C. Brown ◽  
...  

ABSTRACT People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus. IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.


2009 ◽  
Vol 296 (3) ◽  
pp. E473-E479 ◽  
Author(s):  
Yukihiro Fujita ◽  
Rhonda D. Wideman ◽  
Madeleine Speck ◽  
Ali Asadi ◽  
David S. King ◽  
...  

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are released during meals from endocrine cells located in the gut mucosa and stimulate insulin secretion from pancreatic β-cells in a glucose-dependent manner. Although the gut epithelium senses luminal sugars, the mechanism of sugar sensing and its downstream events coupled to the release of the incretin hormones are not clearly elucidated. Recently, it was reported that sucralose, a sweetener that activates the sweet receptors of taste buds, triggers incretin release from a murine enteroendocrine cell line in vitro. We confirmed that immunoreactivity of α-gustducin, a key G-coupled protein involved in taste sensing, is sometimes colocalized with GIP in rat duodenum. We investigated whether secretion of incretins in response to carbohydrates is mediated via taste receptors by feeding rats the sweet-tasting compounds saccharin, acesulfame potassium, d-tryptophan, sucralose, or stevia. Oral gavage of these sweeteners did not reduce the blood glucose excursion to a subsequent intraperitoneal glucose tolerance test. Neither oral sucralose nor oral stevia reduced blood glucose levels in Zucker diabetic fatty rats. Finally, whereas oral glucose increased plasma GIP levels ∼4-fold and GLP-1 levels ∼2.5-fold postadministration, none of the sweeteners tested significantly increased levels of these incretins. Collectively, our findings do not support the concept that release of incretins from enteroendocrine cells is triggered by carbohydrates via a pathway identical to the sensation of “sweet taste” in the tongue.


Author(s):  
Aymen Owais Ghauri ◽  
Saeed Ahmad ◽  
Tayyeba Rehman

AbstractBackgroundDiabetes is the one of the leading cause of morbidity and mortality. Traditionally phytotherapy is widely being used for diabetes treatment and highly valued. Citrus colocynthis has known anti-diabetic potential. However, anti-diabetic potential of hydro-ethanolic extract of C. colocynthis pulpy flesh with seeds is not reported yet.MethodsThe extract of C. colocynthis pulpy flesh with seeds was done by maceration method using 70% ethanol. To evaluate anti-diabetic and antioxidant potential of the seeded fruit in vitro, α-glucosidase and DPPH inhibition assays was done, respectively. In vivo study used streptozotocin (STZ) induced diabetes model of rats. Rats were randomized in five groups i. e. normal control, negative control, standard control, C. colocynthis 150 and 300 mg/kg. STZ was administered to all groups except normal control. After wards, plant extract and glibenclamide is continued for 14 days. Blood samples were collected from rat tail vein daily and from Cardiac puncture at the end of study. The blood glucose levels were monitored daily by using one-touch blood glucose monitoring system. The blood glucose level was monitored on 0, 1st, 5th, 8th, 11th, and 14th day of induction.ResultsHydro-ethanolic extract of C. colocynthis pulpy flesh with seeds was able to decolorize DPPH and therefore possess antioxidant potential, continuous administration for 14 days showed a marked decrease in serum glucose levels (p 0.01) it is found to be somewhat less effective as glibenclamide (standard control) (p 0.001). A time-dependent decrease in blood glucose levels was observed (351.3 ± 4 to 258 m/kg).ConclusionHydro-ethanolic extract of C. colocynthis pulpy flesh with seeds lowered the serum triglyceride and cholesterol levels in diabetic rats significantly as compared to negative control. The hypoglycemic effect of hydro-ethanolic extract of C. colocynthis pulpy flesh with seeds is may be due to α-glucosidase inhibition potential.


1962 ◽  
Vol 203 (6) ◽  
pp. 975-979 ◽  
Author(s):  
Stephen S. Chan ◽  
William D. Lotspeich

The net tubular reabsorption of glucose (TG) was measured simultaneously in both kidneys of the cat before, during, and after the infusion of small amounts of phlorizin and phloretin at constant rates into one renal artery. Experiments were performed at endogenous and elevated blood glucose levels. The results show that phlorizin blocks glucose transport across the renal tubule at concentrations in renal blood and tissue in the range of 10–5 to 10–7 m. These estimates agree with those for dog kidney in vivo and hamster small intestine in vitro. In addition to this high affinity of phlorizin for the tubular glucose carrier, the experiments also reveal the easily dissociable nature of the phlorizin carrier complex. When blood glucose is elevated the TG is even more sensitive to small concentrations of phlorizin. At all blood glucose levels the aglucone, phloretin, is at least ten times less effective in inhibiting TG than phlorizin itself. These findings are discussed in relation to critical groupings in the phlorizin molecule.


2014 ◽  
Vol 92 (6) ◽  
pp. 438-444 ◽  
Author(s):  
Haniah Solaimani ◽  
Nepton Soltani ◽  
Kianoosh MaleKzadeh ◽  
Shahla Sohrabipour ◽  
Nina Zhang ◽  
...  

It has been previously shown that oral magnesium administration decreases the levels of glucose in the plasma. However, the mechanisms are not fully understood. The aim of this study was to determine the potential role of GLUT4 on plasma glucose levels by orally administering magnesium sulfate to diabetic rats. Animals were distributed among 4 groups (n = 10 rats per group): one group served as the non-diabetic control, while the other groups had diabetes induced by streptozotocin (intraperitoneal (i.p.) injection). The diabetic rats were either given insulin by i.p. injection (2.5 U·(kg body mass)–1·day–1), or magnesium sulfate in their drinking water (10 g·L–1). After 8 weeks of treatment, we conducted an i.p. glucose tolerance test (IPGTT), measured blood glucose and plasma magnesium levels, and performed in-vitro and in-vivo insulin level measurements by radioimmunoassay. Gastrocnemius (leg) muscles were isolated for the measurement of GLU4 mRNA expression using real-time PCR. Administration of magnesium sulfate improved IPGTT and lowered blood glucose levels almost to the normal range. However, the insulin levels were not changed in either of the in-vitro or in-vivo studies. The expression of GLU4 mRNA increased 23% and 10% in diabetic magnesium-treated and insulin-treated groups, respectively. Our findings suggest that magnesium lowers blood glucose levels via increased GLU4 mRNA expression, independent to insulin secretion.


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