Glucose transporter expression and regulation following a fast in the ruby-throated hummingbird, Archilochus colubris

ABSTRACTHummingbirds, subsisting almost exclusively on nectar sugar, face extreme challenges to blood sugar regulation. The capacity for transmembrane sugar transport is mediated by the activity of facilitative glucose transporters (GLUTs) and their localisation to the plasma membrane (PM). In this study, we determined the relative protein abundance of GLUT1, GLUT2, GLUT3 and GLUT5 via immunoblot using custom-designed antibodies in whole-tissue homogenates and PM fractions of flight muscle, heart and liver of ruby-throated hummingbirds (Archilochus colubris). The GLUTs examined were detected in nearly all tissues tested. Hepatic GLUT1 was minimally present in whole-tissue homogenates and absent win PM fractions. GLUT5 was expressed in flight muscles at levels comparable to those of the liver, consistent with the hypothesised uniquely high fructose uptake and oxidation capacity of hummingbird flight muscles. To assess GLUT regulation, we fed ruby-throated hummingbirds 1 mol l−1 sucrose ad libitum for 24 h followed by either 1 h of fasting or continued feeding until sampling. We measured relative GLUT abundance and concentration of circulating sugars. Blood fructose concentration in fasted hummingbirds declined (∼5 mmol l−1 to ∼0.18 mmol l−1), while fructose-transporting GLUT2 and GLUT5 abundance did not change in PM fractions. Blood glucose concentrations remained elevated in fed and fasted hummingbirds (∼30 mmol l−1), while glucose-transporting GLUT1 and GLUT3 in flight muscle and liver PM fractions, respectively, declined in fasted birds. Our results suggest that glucose uptake capacity is dynamically reduced in response to fasting, allowing for maintenance of elevated blood glucose levels, while fructose uptake capacity remains constitutively elevated promoting depletion of blood total fructose within the first hour of a fast.

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Glucose Transporter Expression and Regulation Following a Fast in the Ruby-throated Hummingbird, Archilochus colubris

10.1101/2020.06.12.148619 ◽

2020 ◽

Author(s):

Raafay S. Ali ◽

Morag F. Dick ◽

Saad Muhammad ◽

Dylan Sarver ◽

G. William Wong ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Transporter ◽

Flight Muscle ◽

Sugar Transport ◽

Uptake Capacity ◽

High Blood Glucose ◽

Glucose Levels ◽

High Fructose ◽

Sugar Regulation ◽

Ad Libitum

AbstractHummingbirds subsist almost exclusively on nectar sugar and face extreme challenges blood sugar regulation. Transmembrane sugar transport is mediated by facilitative glucose transporters (GLUTs) and the capacity for sugar transport is dependent on both the activity of GLUTs and their localisation to the plasma membrane (PM). In this study, we determined the relative protein abundance in whole-tissue (WT) homogenates and PM fractions via immunoblot using custom antibodies for GLUT1, GLUT2, GLUT3, and GLUT5 in flight muscle, heart, and, liver of ruby-throated hummingbirds (Archilochus colubris). GLUTs examined were detected in nearly all tissues tested. Hepatic GLUT1 was minimally present in WT homogenates and absent in PM fractions. GLUT5 was expressed in hummingbird flight muscles at levels comparable to that of their liver, consistent with the hypothesised uniquely high fructose-uptake and oxidation capacity of this tissue. To assess GLUT regulation, we fed ruby-throated hummingbirds 1M sucrose ad libitum for 24 hours followed by either 1 hour of fasting or continued ad libitum feeding until sampling. We measured relative GLUT abundance and concentrations of circulating sugars. Blood fructose concentration in fasted hummingbirds declined from ∼5mM to ∼0.18mM, while fructose-transporting PM GLUT2 and PM GLUT5 did not change in abundance. Blood glucose concentrations remained elevated in both fed and fasted hummingbirds, at ∼30mM, while glucose-transporting PM GLUT1 and PM GLUT3 in the flight muscle and liver, respectively, declined in fasted birds. Our results suggest that glucose uptake capacity is dynamically reduced in response to fasting, allowing for maintenance of elevated blood glucose levels, while fructose uptake capacity remains constitutively elevated promoting depletion of blood total fructose within the first hour of a fast.Summary statementHummingbird ingest nectar rich in glucose and fructose. When fasted, tissue capacity for circulating glucose import declines while remaining elevated for fructose. This may underlie maintenance of high blood glucose and rapid depletion of blood fructose.

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Effect of Addition of WZB117 as an Inhibitor of Glucose Transporter 1 for Venous Blood Glucose Determination

Laboratory Medicine ◽

10.1093/labmed/lmaa051 ◽

2020 ◽

Author(s):

Lei Zhang ◽

Yaqiong Ran ◽

Yan Zhu ◽

Qianna Zhen

Keyword(s):

Blood Glucose ◽

Glucose Level ◽

Glucose Transporter ◽

Venous Blood ◽

Sugar Transport ◽

Glucose Transporter 1 ◽

Glucose Determination ◽

Glucose Levels ◽

Significant Difference ◽

Blood Glucose Determination

Abstract Objective Sodium fluoride (NaF) has been applied to inhibit glycolysis in venous specimens for decades. However, it has had little effect on the rate of glycolysis in the first 1 to 2 hours, resulting in a decrease of glucose, so a more efficient method is needed. Recently, we discovered that WZB117, a specific Glut1 inhibitor, restricts glycolysis by inhibiting the passive sugar transport of human red blood cells and cancer cells. The purpose of this study was to evaluate the results of intravenous blood glucose determination after the addition of WZB117. Methods Venous specimens from 40 pairs of healthy volunteers were collected for several days and placed in tubes containing NaF plus EDTA-disodium (Na2) without WZB117 (the A group); citric acid, trisodium citrate, and EDTA-Na2 without WZB117 (B group); and NaF plus EDTA-Na2 with WZB117 (C group). The glucose concentration was measured after venipuncture and compared with test tubes treated for 1 hour, 2 hours, and 3 hours before centrifugation. Glucose level was determined by the hexokinase method. The paired t-test was used to examine differences in glucose values at baseline and at different time points. The number of misdiagnoses and the misdiagnosis rate were calculated at 2 diagnostic stages: high risk of diabetes (glucose level of 6.1 mmol/L) and diagnosis of diabetes (glucose level of 7.0 mmol/L). Results Glucose levels decreased by 1.0% at 1 hour and by 2.1% at 3 hours in the C group tubes and simultaneously decreased by 1.7% at 1 hour and by 2.5% at 3 hours in the B group tubes. In contrast, glucose levels decreased by 4.1% at 1 hour and by 6.3% at 3 hours in the A group tubes. There was a statistically significant difference in glucose levels measured in the A group tubes and B group tubes at 1 hour, 2 hours, and 3 hours. The misdiagnosis rate of clinical diagnosis in diabetes was highest in the A group tubes (7.0‰ at 1 hour, 0.1‰ at 3 hours at 7.0 mmol/L point; 14.6‰ at 1 hour, 0.4‰ at 3 hours at 6.1 mmol/L point) and lowest in the C group tubes (2.95‰ at 1 hour, 0‰ at 3 hours at 7.0 mmol/L point; 4.8‰ at 1 hour, 0.1‰ at 3 hours at 6.1 mmol/L point). Conclusion The tube addition of WZB117 is more suitable for minimizing glycolysis and has no effect on glucose levels even if specimens are left uncentrifuged for up to 3 hours.

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A Nutraceutical Combination of Cinnamon, Purple Onion, and Tea Linked with Key Enzymes on Treatment of Type 2 Diabetes

10.21203/rs.3.rs-321421/v1 ◽

2021 ◽

Author(s):

Lebin Weng ◽

Ting-Hsu Chen ◽

Liyue Huang ◽

Dong Lai ◽

Yaw-Syan Fu ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Maximal Response ◽

Oral Glucose ◽

Postprandial Plasma Glucose ◽

Glucose Levels ◽

High Fructose ◽

Tea Extract

Abstract Background: Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause adverse effects. This study explores the efficacy of polyherbal dietary supplement cinnamon, purple onion, and tea on the mediation of postprandial hyperglycemia for in the search of combinations with a maximal response. Materials and methods: A starch solution (3 g/kg Bwt) of oral starch tolerance test (OSTT) and glucose solution (4 g/kg Bwt) of oral glucose tolerance test (OGTT) with and without cinnamon, purple onion, tea extract (15 mg/kg Bwt), and mixture (each 5 mg/kg Bwt, 1:1:1), metformin (14 mg/kg Bwt), or acarbose (50 mg/kg Bwt) was administered to high fat plus high fructose-induced diabetic mice after an overnight fast. Postprandial plasma glucose levels were measured and incremental areas under the response curve were calculated. Results: Compared with acarbose, the mixture of extracts (purple onion, cinnamon, and tea) indicated decreasing blood glucose in OSTT. In OGTT, the mixture of extracts showed greater efficacy for hypoglycemia when compared with metformin. The molecular docking of α-Amylase, α-Glucosidase, and AMPK confirmed the putatively acting molecules from the extracts of purple onion, cinnamon, and tea. Conclusions: Overall, this investigation evidenced a beneficial mediation for the progression of lowering blood glucose with a combinatory extract of cinnamon, dietary onion, and tea, implicating their prospective as nutraceuticals that might ameliorate hyperglycemia in diabetes.

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A study to evaluate the antidiabetic effect of Syzygium cumini Linn. seed extract in high fructose diet induced diabetes in Albino Rats

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20172224 ◽

2017 ◽

Vol 6 (6) ◽

pp. 1363

Author(s):

Sandeep Vihan ◽

D. B. S. Brashier

Keyword(s):

Blood Glucose ◽

Phase I ◽

Seed Extract ◽

Syzygium Cumini ◽

Antidiabetic Effect ◽

High Fructose Diet ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Group I ◽

High Fructose

Background: The objective of the study was to evaluate the antidiabetic effect of syzygium cumini linn. Seed extract in high fructose diet induced diabetes in albino rats.Methods: This study was conducted in two phases. In Phase I acute and chronic effects of three doses of Syzygium cumini Linn 200mg/kg, 400mg/kg and 800mg/kg was seen in euglycaemic rats. In Phase II, the above doses of Syzygium cumini Linn were seen in diabetes induced by high fructose diet was evaluated. 5 groups of 06 animals each. Group I was given normal saline orally. Group II, III and IV were given oral Syzygium extract in the dose of 200mg/kg, 400mg/kg and 800mg/Kg respectively. Group V was given glibenclamide suspension 10 mg/Kg orally. Blood glucose was measured before starting this phase (Day 0), at the end of fructose feeding (day 28) and weekly thereafter up to the end of the treatment period (i.e. on days 35,42,49,56).Results: In phase I of the study, Syzygium extract had no effect on the mean blood glucose levels when given in the doses of 200, 400 and 800 mg/kg, from 1-24 hours. After chronic administration to euglycemic rats for 4 weeks, Syzygium extract also did not produce any significant change in blood glucose levels when given at various doses from 200-800 mg/kg. Treatment with all the three doses of Syzygium cumini extract (200,400 and 800mg/kg) produced a significant reduction in the blood glucose level. (P value <0.001 as compared to group I). The glucose lowering effect started at the end of 1 weeks and it increased till the end of the study in all the groups.Conclusions: Syzygium cumini Linn extract has no effect on the blood glucose levels of euglycemic animals. Syzygium cumini Linn extract can reduce blood glucose levels in high fructose diet induced diabetic rats, in a dose dependent and time dependent manner.

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Mirtazapine Reduces Adipocyte Hypertrophy and Increases Glucose Transporter Expression in Obese Mice

Animals ◽

10.3390/ani10081423 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1423 ◽

Cited By ~ 1

Author(s):

Ching-Feng Wu ◽

Po-Hsun Hou ◽

Frank Chiahung Mao ◽

Yao-Chi Su ◽

Ching-Yang Wu ◽

...

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Weight Control ◽

Glucose Transporter ◽

Kidney Diseases ◽

Serum Triglyceride ◽

Fat Cell ◽

Glucose Levels ◽

Positive Effects ◽

Blood Glucose Levels

Metabolic syndrome is known to engender type 2 diabetes as well as some cardiac, cerebrovascular, and kidney diseases. Mirtazapine—an atypical second-generation antipsychotic drug with less severe side effects than atypical first-generation antipsychotics—may have positive effects on blood glucose levels and obesity. In our executed study, we treated male high-fat diet (HFD)-fed C57BL/6J mice with mirtazapine (10 mg/kg/day mirtazapine) for 4 weeks to understand its antiobesity effects. We noted these mice to exhibit lower insulin levels, daily food efficiency, body weight, serum triglyceride levels, aspartate aminotransferase levels, liver and epididymal fat pad weight, and fatty acid regulation marker expression when compared with their counterparts (i.e., HFD-fed control mice). Furthermore, we determined a considerable drop in fatty liver scores and mean fat cell size in the epididymal white adipose tissue in the treated mice, corresponding to AMP-activated protein kinase expression activation. Notably, the treated mice showed lower glucose tolerance and blood glucose levels, but higher glucose transporter 4 expression. Overall, the aforementioned findings signify that mirtazapine could reduce lipid accumulation and thus prevent HFD-induced increase in body weight. In conclusion, mirtazapine may be useful in body weight control and antihyperglycemia therapy.

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Insulin Mimetic Properties of Extracts Prepared from Bellis perennis

Molecules ◽

10.3390/molecules23102605 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2605 ◽

Cited By ~ 5

Author(s):

Renate Haselgrübler ◽

Verena Stadlbauer ◽

Flora Stübl ◽

Bettina Schwarzinger ◽

Ieva Rudzionyte ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Transporter ◽

Living Organism ◽

Cell System ◽

Glut4 Translocation ◽

In Ovo ◽

Screening Assay ◽

Glucose Levels ◽

Blood Glucose Levels

Diabetes mellitus (DM) and consequential cardiovascular diseases lead to millions of deaths worldwide each year; 90% of all people suffering from DM are classified as Type 2 DM (T2DM) patients. T2DM is linked to insulin resistance and a loss of insulin sensitivity. It leads to a reduced uptake of glucose mediated by glucose transporter 4 (GLUT4) in muscle and adipose tissue, and finally hyperglycemia. Using a fluorescence microscopy-based screening assay we searched for herbal extracts that induce GLUT4 translocation in the absence of insulin, and confirmed their activity in chick embryos. We found that extracts prepared from Bellis perennis (common daisy) are efficient inducers of GLUT4 translocation in the applied in vitro cell system. In addition, these extracts also led to reduced blood glucose levels in chicken embryos (in ovo), confirming their activity in a living organism. Using high-performance liquid chromtaography (HPLC) analysis, we identified and quantified numerous polyphenolic compounds including apigenin glycosides, quercitrin and chlorogenic acid, which potentially contribute to the induction of GLUT4 translocation. In conclusion, Bellis perennis extracts reduce blood glucose levels and are therefore suitable candidates for application in food supplements for the prevention and accompanying therapy of T2DM.

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Identification of Insulin-Mimetic Plant Extracts: From an In Vitro High-Content Screen to Blood Glucose Reduction in Live Animals

Molecules ◽

10.3390/molecules26144346 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4346

Author(s):

Verena Stadlbauer ◽

Cathrina Neuhauser ◽

Tobias Aumiller ◽

Alexander Stallinger ◽

Marcus Iken ◽

...

Keyword(s):

Plasma Membrane ◽

Blood Glucose ◽

Plant Extracts ◽

Glucose Transporter ◽

Glut4 Translocation ◽

In Ovo ◽

Insulin Mimetic ◽

Glucose Levels ◽

Intracellular Translocation

Type 2 diabetes mellitus (T2DM) is linked to insulin resistance and a loss of insulin sensitivity, leading to millions of deaths worldwide each year. T2DM is caused by reduced uptake of glucose facilitated by glucose transporter 4 (GLUT4) in muscle and adipose tissue due to decreased intracellular translocation of GLUT4-containing vesicles to the plasma membrane. To treat T2DM, novel medications are required. Through a fluorescence microscopy-based high-content screen, we tested more than 600 plant extracts for their potential to induce GLUT4 translocation in the absence of insulin. The primary screen in CHO-K1 cells resulted in 30 positive hits, which were further investigated in HeLa and 3T3-L1 cells. In addition, full plasma membrane insertion was examined by immunostaining of the first extracellular loop of GLUT4. The application of appropriate inhibitors identified PI3 kinase as the most important signal transduction target relevant for GLUT4 translocation. Finally, from the most effective hits in vitro, four extracts effectively reduced blood glucose levels in chicken embryos (in ovo), indicating their applicability as antidiabetic pharmaceuticals or nutraceuticals.

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Inhibition of the intestinal postprandial glucose transport by gallic acid and gallic acid derivatives

Food & Function ◽

10.1039/d1fo01118a ◽

2021 ◽

Author(s):

huijun Wang ◽

Mark I Fowler ◽

David J Messenger ◽

Jose Juan Ordaz-Ortiz ◽

Xuelan Gu ◽

...

Keyword(s):

Blood Glucose ◽

Gallic Acid ◽

Glucose Transporter ◽

Postprandial Glucose ◽

Postprandial Blood Glucose ◽

Glucose Transporter 1 ◽

Glucose Levels ◽

Glucose Transporter 2 ◽

Blood Glucose Levels ◽

Sodium Dependent

Inhibition of glucose uptake in the intestine through sodium-dependent glucose transporter 1 (SGLT1) or glucose transporter 2 (GLUT2) may be beneficial in controlling postprandial blood glucose levels. Gallic acid and...

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The synaptic vesicle protein, cysteine-string protein, is associated with the plasma membrane in 3T3-L1 adipocytes and interacts with syntaxin 4

Journal of Cell Science ◽

10.1242/jcs.114.2.445 ◽

2001 ◽

Vol 114 (2) ◽

pp. 445-455

Author(s):

L.H. Chamberlain ◽

M.E. Graham ◽

S. Kane ◽

J.L. Jackson ◽

V.H. Maier ◽

...

Keyword(s):

Plasma Membrane ◽

Blood Glucose ◽

Glucose Transporter ◽

Cell Types ◽

Secretory Vesicle ◽

Insulin Stimulation ◽

Glucose Levels ◽

Cysteine String Protein ◽

Syntaxin 4 ◽

Vesicle Protein

Adipocytes and muscle cells play a major role in blood glucose homeostasis. This is dependent upon the expression of Glut4, an insulin-responsive facilitative glucose transporter. Glut4 is localised to specialised intracellular vesicles that fuse with the plasma membrane in response to insulin stimulation. The insulin-induced translocation of Glut4 to the cell surface is essential for the maintenance of optimal blood glucose levels, and defects in this system are associated with insulin resistance and type II diabetes. Therefore, a major focus of recent research has been to identify and characterise proteins that regulate Glut4 translocation. Cysteine-string protein (Csp) is a secretory vesicle protein that functions in presynaptic neurotransmission and also in regulated exocytosis from non-neuronal cells. We show that Csp1 is expressed in 3T3-L1 adipocytes and that cellular levels of this protein are increased following cell differentiation. Combined fractionation and immunofluorescence analyses reveal that Csp1 is not a component of intracellular Glut4-storage vesicles (GSVs), but is associated with the adipocyte plasma membrane. This association is stable, and not affected by either insulin stimulation or chemical depalmitoylation of Csp1. We also demonstrate that Csp1 interacts with the t-SNARE syntaxin 4. As syntaxin 4 is an important mediator of insulin-stimulated GSV fusion with the plasma membrane, this suggests that Csp1 may play a regulatory role in this process. Syntaxin 4 interacts specifically with Csp1, but not with Csp2. In contrast, syntaxin 1A binds to both Csp isoforms, and actually exhibits a higher affinity for the Csp2 protein. The results described raise a number of interesting questions concerning the intracellular targeting of Csp in different cell types, and suggest that the composition and synthesis of GSVs may be different from synaptic and other secretory vesicles. In addition, the interaction of Csp1 with syntaxin 4 suggests that this Csp isoform may play a role in insulin-stimulated fusion of GSVs with the plasma membrane.

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Lysulin: Natural nutritional support to bring better health to people with diabetes and prediabetes

Bioactive Compounds in Health and Disease ◽

10.31989/bchd.v2i6.600 ◽

2019 ◽

Vol 2 (6) ◽

pp. 149

Author(s):

John Frederick Burd

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Nutritional Support ◽

Nutritional Supplements ◽

Double Blind ◽

Glucose Levels ◽

Blood Glucose Levels ◽

High Fructose ◽

Diet And Exercise

Obesity and type 2 diabetes, both worldwide epidemics, are drastic problems that can be ameliorated dramatically through the combination of lifestyle changes (especially diet and exercise) the treatment of drugs and nutritional supplements [1]. Lysulin is a patent-pending nutritional supplement that contains lysine, zinc and vitamin C [2]. Through double-blind placebo-controlled studies, it has been shown to help people with prediabetes [3] and type 2 diabetes [4] in promoting better glycemic control and lowering their HbA1c.Historically, supplements have had a bad reputation due to aggressive marketing of unsubstantiated claims. That being said, Lysulin is firmly grounded on a foundation of 25 years of research, development and clinical studies. These studies show the ingredients in Lysulin can lower blood glucose and glycated proteins – the cause of diabetes complications. In addition, double-blind placebo-controlled studies found that Lysulin improves glycemic control in people with diabetes and may also slow or even halt the progression from prediabetes to type 2 diabetes [3,4].Glucose is essential in providing the human body an energy source. Glucose relies on the hormone, insulin, to enter our cells to provide the energy we need for everyday living. However, while everyone needs a certain amount of glucose for daily energy production, excessive glucose is dangerously toxic to the body (primarily as a result of protein glycation). In addition, fructose (from High Fructose Corn Syrup) does not utilize insulin to enter the liver or our cells, and thus enters them easily and immediately turns into fat [5]. Poor diets, along with increased consumption of High Fructose Corn Syrup (HFCS), have lead to the high rates of obesity and diabetes that we see today. The pandemic of type 2 diabetes, which is expected to affect at least 250 million people worldwide by 2020 and 642 million by 2040 [6], is the result of diets high in carbohydrates, HFCS and sugar, along with the lack of commensurate exercise. This lifestyle leads to insulin resistance, caused by the glycation of insulin and insulin receptors [7], which results in high concentrations of glucose in the bloodstream. The therapy for type 2 diabetes begins with attempts to control glucose through diet and exercise. If this fails, oral drugs are prescribed. If these fail to show improvements in blood glucose levels, insulin injections are given. Over 30% of people with type 2 diabetes are using insulin injections to control their blood glucose levels [6]. There is vast literature documenting the role of nutraceuticals and functional foods in managing the alterations in metabolism and improving the health of people with chronic disease [8, 9]. To make up for the fact that important nutrients are lost during the processing of food, adding nutritional supplements to our daily routine, in addition to consuming a low-carbohydrate diet, can have profound benefits. A well-balanced diet, along with exercise and the right nutritional supplements, can provide the foundation for a lifetime of well-being and good health.Keywords: Diabetes, Nutritional Support, Lysulin, Lysine, Zinc, Vitamin V, HbA1c

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