Comparative effects of phlorizin and phloretin on glucose transport in the cat kidney

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.

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hye-Won Yang ◽  
Yun-Fei Jiang ◽  
Hyo-Geun Lee ◽  
You-Jin Jeon ◽  
BoMi Ryu

Diphlorethohydroxycarmalol (DPHC), a type of phlorotannin isolated from the marine alga Ishige okamurae, reportedly alleviates impaired glucose tolerance. However, the molecular mechanisms of DPHC regulatory activity and by which it exerts potential beneficial effects on glucose transport into skeletal myotubes to control glucose homeostasis remain largely unexplored. The aim of this study was to evaluate the effect of DPHC on cytosolic Ca2+ levels and its correlation with blood glucose transport in skeletal myotubes in vitro and in vivo. Cytosolic Ca2+ levels upon DPHC treatment were evaluated in skeletal myotubes and zebrafish larvae by Ca2+ imaging using Fluo-4. We investigated the effect of DPHC on the blood glucose level and glucose transport pathway in a hyperglycemic zebrafish. DPHC was shown to control blood glucose levels by accelerating glucose transport; this effect was associated with elevated cytosolic Ca2+ levels in skeletal myotubes. Moreover, the increased cytosolic Ca2+ level caused by DPHC can facilitate the Glut4/AMPK pathways of the skeletal muscle in activating glucose metabolism, thereby regulating muscle contraction through the regulation of expression of troponin I/C, CaMKII, and ATP. Our findings provide insights into the mechanism of DPHC activity in skeletal myotubes, suggesting that increased cytosolic Ca2+ levels caused by DPHC can promote glucose transport into skeletal myotubes to modulate blood glucose levels, thus indicating the potential use of DPHC in the prevention of diabetes.


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.


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.


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.


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.


Planta Medica ◽  
2020 ◽  
Vol 86 (11) ◽  
pp. 790-799
Author(s):  
István Takács ◽  
András Szekeres ◽  
Ákos Takács ◽  
Dávid Rakk ◽  
Miklós Mézes ◽  
...  

AbstractIntestinal α-glucosidase and α-amylase break down nutritional poly- and oligosaccharides to monosaccharides and their activity significantly contributes to postprandial hyperglycemia. Competitive inhibitors of these enzymes, such as acarbose, are effective antidiabetic drugs, but have unpleasant side effects. In our ethnopharmacology inspired investigations, we found that wild strawberry (Fragaria vesca), blackberry (Rubus fruticosus), and European blueberry (Vaccinium myrtillus) leaf extracts inhibit α-glucosidase and α-amylase enzyme activity in vitro and are effective in preventing postprandial hyperglycemia in vivo. Toxicology tests on H9c2 rat embryonic cardiac muscle cells demonstrated that berry leaf extracts have no cytotoxic effects. Oral administration of these leaf extracts alone or as a mixture to normal (control), obese, prediabetic, and streptozotocin-induced diabetic mice attenuated the starch-induced rise of blood glucose levels. The efficiency was similar to that of acarbose on blood glucose. These results highlight berry leaf extracts as candidates for testing in clinical trials in order to assess the clinical significance of their effects on glycemic control.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Zhi-Long Shi ◽  
Yi-Dan Liu ◽  
Yun-Yun Yuan ◽  
Da Song ◽  
Mei-Feng Qi ◽  
...  

Norathyriol is a metabolite of mangiferin. Mangiferin has been reported to inhibit α-glucosidase. To the best of our knowledge, no study has been conducted to determine or compare those two compounds on inhibiting α-glucosidase in vitro and in vivo by far. In this study, we determined the inhibitory activity of norathyriol and mangiferin on α-glucosidase in vitro and evaluated their antidiabetic effect in diabetic mice. The results showed that norathyriol inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 3.12 μM, which is more potent than mangiferin (IC50 = 358.54 μM) and positive drug acarbose (IC50 = 479.2 μM) in the zymological experiment. Both of norathyriol and mangiferin caused significant (p<0.05) reduction in fasting blood glucose and the blood glucose levels at two hours after carbohydrate loading and it was interesting that mangiferin and norathyriol can make the decline of the blood glucose earlier than other groups ever including normal group in the starch tolerance test. However, norathyriol and mangiferin did not significantly influence carbohydrate absorption in the glucose tolerance test. Therefore, the antidiabetic effects of norathyriol and mangiferin might be associated with α-glucosidase, and norathyriol was more potent than mangiferin.


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