scholarly journals Mucin-Grafted Polyethylene Glycol Microparticles Enable Oral Insulin Delivery for Improving Diabetic Treatment

2020 ◽  
Vol 10 (8) ◽  
pp. 2649 ◽  
Author(s):  
Momoh A. Mumuni ◽  
Ugwu E. Calister ◽  
Nafiu Aminu ◽  
Kenechukwu C. Franklin ◽  
Adedokun Musiliu Oluseun ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Oral Delivery ◽  
Subcutaneous Administration ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Insulin Solution ◽  
Diabetic Treatment ◽  
Short Time

In this study, different ratios of mucin-grafted polyethylene-glycol-based microparticles were prepared and evaluated both in vitro and in vivo as carriers for the oral delivery of insulin. Characterization measurements showed that the insulin-loaded microparticles display irregular porosity and shape. The encapsulation efficiency and loading capacity of insulin were >82% and 18%, respectively. The release of insulin varied between 68% and 92% depending on the microparticle formulation. In particular, orally administered insulin-loaded microparticles resulted in a significant fall of blood glucose levels, as compared to insulin solution. Subcutaneous administration showed a faster, albeit not sustained, glucose fall within a short time as compared to the polymeric microparticle-based formulations. These results indicate the possible oral delivery of insulin using this combination of polymers.

scholarly journals “Oil-soluble” Reversed Lipid Nanoparticles for Oral Insulin Delivery

2020 ◽  
Author(s):  
Tao Wang ◽  
Dongqin Quan
Keyword(s):  
Oral Absorption ◽  
Insulin Delivery ◽  
Lipid Nanoparticles ◽  
Oral Insulin ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Transmission Electron ◽  
Insulin Solution

Abstract Background In this study, we aimed to design a novel oral insulin delivery system, named “oil-soluble” reversed lipid nanoparticles (ORLN), in which a hydrophilic insulin molecule is encapsulated by a phospholipid (PC) shell and dissolved in oil to prevent the enzymatic degradation of insulin. ORLN was characterized by transmission electron microscopy and dynamic light scattering. Results In vitro enzymatic stability studies showed higher concentrations of insulin in cells incubated with ORLN-encapsulated insulin than in those incubated with free insulin solution in artificial intestinal fluid (pH 6.5). The protective effect of ORLN was attributed to its special release behavior and the formulation of the PC shell and oil barrier. Furthermore, an in vivo oral efficacy study confirmed that blood glucose levels were markedly decreased after ORLN administration in both healthy and diabetic mice. In vivo pharmacokinetic results showed that the bioavailability of ORLN-conjugated insulin was approximately 28.7% relative to that of the group subcutaneously administered with an aqueous solution of insulin, indicating enhanced oral absorption. Conclusions In summary, the ORLN system developed here shows promise as a nanocarrier for improving the oral absorption of insulin.

scholarly journals “Oil-soluble” Reversed Lipid Nanoparticles for Oral Insulin Delivery

2020 ◽  
Author(s):  
Tao Wang ◽  
Liao Shen ◽  
Yadan Zhang ◽  
Haiyan Li ◽  
Yongan Wang ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Insulin Delivery ◽  
Lipid Nanoparticles ◽  
Oral Insulin ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Transmission Electron ◽  
Insulin Solution

Abstract Background: In this study, we aimed to design a novel oral insulin delivery system, named “oil-soluble” reversed lipid nanoparticles (ORLN), in which a hydrophilic insulin molecule is encapsulated by a phospholipid (PC) shell and dissolved in oil to prevent the enzymatic degradation of insulin. ORLN was characterized by transmission electron microscopy and dynamic light scattering. Results: In vitro enzymatic stability studies showed higher concentrations of insulin in cells incubated with ORLN-encapsulated insulin than in those incubated with free insulin solution in artificial intestinal fluid (pH 6.5). The protective effect of ORLN was attributed to its special release behavior and the formulation of the PC shell and oil barrier. Furthermore, an in vivo oral efficacy study confirmed that blood glucose levels were markedly decreased after ORLN administration in both healthy and diabetic mice. In vivo pharmacokinetic results showed that the bioavailability of ORLN-conjugated insulin was approximately 28.7% relative to that of the group subcutaneously administered with an aqueous solution of insulin, indicating enhanced oral absorption.Conclusions: In summary, the ORLN system developed here shows promise as a nanocarrier for improving the oral absorption of insulin.

scholarly journals Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (6) ◽  
pp. 1517 ◽  
Author(s):  
Kai Wang ◽  
Yu Su ◽  
Yuting Liang ◽  
Yanhui Song ◽  
Liping Wang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Enzymatic Activity ◽  
Glucose Levels ◽  
Blood Glucose Levels

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.

scholarly journals Glycemic Variability in Diabetes Increases the Severity of Influenza

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Rebecca J. Marshall ◽  
Pornthida Armart ◽  
Katina D. Hulme ◽  
Keng Yih Chew ◽  
Alexandra C. Brown ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glycemic Variability ◽  
Endothelial Barrier ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Severe Influenza ◽  
Increased Risk ◽  
History Of

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.

scholarly journals ANTI-DIABETIC EFFECTS OF GLUCOMANNO-OLIGOSACCHARIDES VIA AMPK ACTIVATION IN C2C12 MYOTUBES

2021 ◽  
Vol 59 (4) ◽  
pp. 467
Author(s):  
Thien Truong Do ◽  
Nu Thi Tran ◽  
Que Nguyet Thi Do ◽  
Nhi Thi Y Tran
Keyword(s):  
C2c12 Myotubes ◽  
Control Group ◽  
Ampk Activation ◽  
Independent Manner ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Ampk Phosphorylation ◽  
Amp Activated Protein Kinase

Abstract-HCTN7. In this paper, antidiabetic activities of glucomanno-oligosaccharides (GMO) in vitro and in vivo were investigated. GMO significantly increased AMP-activated protein kinase (AMPK) phosphorylation in a concentration-independent manner. Treatment with 100μg/ml and 50μg/ml of GMO for 1 hour caused 1.47-fold and 1.81-fold phosphorylation of AMPK, respectively. Oral administration of GMO (6g/kg-1 of body weight day-1) lowered blood glucose levels (p < 0.05) at 120 min as compared to control group. These results suggested that GMO exhibited anti-diabetic effects via activation of AMPK and could be useful for diabetes prevention

In vitro and in vivo anti-diabetic activity of Citrullus colocynthis pulpy flesh with seeds hydro-ethanolic extract

2020 ◽  
Vol 17 (2) ◽  
Author(s):  
Aymen Owais Ghauri ◽  
Saeed Ahmad ◽  
Tayyeba Rehman
Keyword(s):  
Blood Glucose ◽  
Normal Control ◽  
Ethanolic Extract ◽  
Negative Control ◽  
Antioxidant Potential ◽  
Blood Glucose Monitoring ◽  
Glucose Levels ◽  
Blood Glucose Levels

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.

Determination the limit of postprandial blood glucose increase and the metabolism of acetylated wheat starch on healthy mice

2019 ◽  
pp. 15-22
Author(s):  
Khoa Bao Chau Thai ◽  
Huu Tien Nguyen ◽  
Huu Dung Tran
Keyword(s):  
Blood Glucose ◽  
Wheat Starch ◽  
Postprandial Blood Glucose ◽  
Control Group ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Treatment Of Diabetes ◽  
Resistant Starches

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

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
Keyword(s):  
Blood Glucose ◽  
Glucose Transport ◽  
Renal Tubule ◽  
Tubular Reabsorption ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Dog Kidney ◽  
Glucose Carrier

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.

scholarly journals Eurotium Cristatum Fermented Okara as a Potential Food Ingredient to Combat Diabetes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Li Yan Chan ◽  
Masaki Takahashi ◽  
Pei Jean Lim ◽  
Shinya Aoyama ◽  
Saneyuki Makino ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Postprandial Blood Glucose ◽  
Food Ingredient ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Reduce Blood Glucose ◽  
Good Nutrition ◽  
Physical Attributes

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.

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