Altered renal expression of the insulin-responsive glucose transporter GLUT4 in experimental diabetes mellitus

1994 ◽  
Vol 267 (5) ◽  
pp. F816-F824 ◽  
Author(s):  
R. G. Marcus ◽  
R. England ◽  
K. Nguyen ◽  
M. J. Charron ◽  
J. P. Briggs ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Experimental Diabetes Mellitus ◽  
Early Diabetes ◽  
Glut4 Expression ◽  
Microvascular Cells ◽  
Glucose Transporter Glut4

Because the insulin-responsive glucose transporter, GLUT4, is expressed in renal vascular and glomerular cells, we determined the effects of experimental diabetes mellitus on GLUT4 expression and glucose uptake by these tissues. Quantitative reverse-transcription polymerase chain reaction studies of microdissected afferent microvessels and renal glomeruli showed that, after 1 wk of diabetes, GLUT4 mRNA was decreased to 26 and 34% of control values, respectively. GLUT4 immunoblots of renal glomerular and microvessel samples showed that GLUT4 polypeptide was decreased to 51% of control values. These results were confirmed by indirect immunofluorescence, which showed decreased GLUT4 expression in glomerular cells and in vascular smooth muscle cells of the afferent microvasculature of diabetic animals. Uptake of the glucose analogue, 2-deoxyglucose, was also depressed in microvessels of diabetic rats to 57% of control values, supporting the conclusion that fewer total glucose transporters were available for glucose uptake into diabetic renal glomerular and microvascular cells. Thus both GLUT4 expression and glucose uptake by glomerular and microvascular cells are decreased in diabetic animals. These results have led us to suggest a mechanism by which decreased renal GLUT4 expression could contribute to glomerular hyperfiltration and hypertension seen in early diabetes.

Effect of Curcuma longa and Galega orientalis on renal function in rats with experimental diabetes mellitus and acute renal failure

2019 ◽  
pp. 88-95
Author(s):  
Р.И. Айзман ◽  
А.П. Козлова ◽  
Е.И. Гордеева ◽  
М.С. Головин ◽  
Г.А. Корощенко ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Experimental Diabetes ◽  
Curcuma Longa ◽  
Diabetic Rats ◽  
Standard Diet ◽  
Experimental Diabetes Mellitus ◽  
Galega Orientalis

Цель - исследование влияния куркумы длинной и галеги восточной на осмо- и ионорегулирующую функции почек крыс при аллоксан-индуцированном сахарном диабете и острой почечной недостаточности в эксперименте. Методика. Эксперименты выполнены на самцах крыс Wistar (n=70) с моделью сахарного диабета (1-я серия) и острой почечной недостаточности (2-я серия). В обеих сериях животные были поделены на 3 группы: крыс 1-й группы содержали на стандартном корме, крысам остальных групп в корм добавляли куркуму (2-я группа) или галегу (3-я группа) (2% от массы корма). На 7-е сут эксперимента проводили исследование диуретической и ионоуретической функций почек натощак и после 5% водной нагрузки. Концентрацию ионов в моче и плазме определяли методом пламенной фотометрии; осмотическую концентрацию биологических жидкостей - методом криоскопии; биохимические показатели крови - колориметрическим методом. Результаты. У животных с сахарным диабетом фоновый диурез, а также экскреция натрия и калия были статистически значимо выше, чем у контрольных животных. При острой почечной недостаточности наблюдался более низкий уровень диуреза и ионоуреза, особенно после водной нагрузки. Прием куркумы и галеги вызывал улучшение осмо- и ионорегулирующей функции почек у крыс с сахарным диабетом, и практически не влиял на эти функции почек при острой почечной недостаточности. Заключение. При сахарном диабете оба фитопрепарата вызывали понижение концентрации глюкозы, креатинина, мочевины и улучшение ионно-осмотических показателей плазмы крови, при этом эффект куркумы был выражен отчетливее. При острой почечной недостаточности эти фитопрепараты не давали описанного эффекта. Aim. To study effects of the phytomedicines, Curcuma longa and Galega orientalis, on osmosis- and ion-regulating renal functions in rats with experimental diabetes mellitus (DM) and acute renal failure (ARF). Methods. Experiments were performed in two series on Wistar male rats (n=70) with modeled diabetes mellitus (series 1) and acute renal failure (series 2). In each series, the animals were divided into 3 groups, 1) rats of group 1 receiving a standard diet; 2) rats of groups 2 and 3 receiving a standard diet supplemented with turmeric or galega (2% of food weight), respectively. On the 7th day of the experiment, the diuretic and ionuretic renal function was studied in fasting state and after 5% water loading. Concentrations of ions in urine and plasma were determined by flame photometry; osmotic concentrations of biological fluids were measured by cryoscopy; blood biochemical parameters were measured by colorimetry. Results. In diabetic rats, background diuresis and sodium and potassium excretion were significantly higher than in the control animals. In rats with acute renal failure, diuresis and ionuresis were significantly lower, particularly after the water loading. Turmeric and galega supplementation improved the osmotic and ion-regulating renal function in diabetic rats and left practically unchanged these functions in rats with acute renal failure. Conclusion. In rats with diabetes mellitus, both herbal remedies reduced concentrations of glucose, creatinine, and urea and improved ion-osmotic parameters of blood plasma with a more pronounced effect of turmeric. In acute renal failure, these phytomedicines did not produce the described effects.

The tyrosine kinase inhibitor crizotinib influences blood glucose and mRNA expression of GLUT4 and PPARs in the heart of rats with experimental diabetes

2020 ◽  
Author(s):  
Katarina Hadova ◽  
Lucia Mesarosova ◽  
Eva Kralova ◽  
Gabriel Doka ◽  
Peter Krenek ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Mrna Expression ◽  
Tyrosine Kinases ◽  
Glucose Transporter ◽  
Kinase Inhibitor ◽  
Experimental Diabetes ◽  
Cardiac Metabolism ◽  
Diabetic Rats ◽  
C Peptide ◽  
Glucose Transporter Glut4

Tyrosine kinases inhibitors (TKIs) may alter glycaemia and may be cardiotoxic with importance in diabetic heart. We investigated the effect of multi-TKI crizotinib after short-term administration on metabolic modulators of the heart of diabetic rats. Experimental diabetes mellitus (DM) was induced by streptozotocin (STZ; 80 mg/kg, i.p.), controls received vehicle (CON). Three days after STZ, crizotinib (STZ+CRI; 25 mg/kg/day p.o.) or vehicle was administered for 7 days. Blood glucose, C-peptide and glucagon were assessed in plasma samples. Receptor tyrosine kinases (RTKs), cardiac glucose transporters and PPARs were determined in rat left ventricle by RT-qPCR method. Crizotinib moderately reduced blood glucose (by 25%, P<0.05) when compared to STZ rats. The drug did not affect levels of C-peptide, an indicator of insulin secretion, suggesting altered tissue glucose utilization. Crizotinib had no impact on cardiac RTKs. However, an mRNA downregulation of insulin-dependent glucose transporter Glut4 in hearts of STZ rats was attenuated after crizotinib treatment. Moreover, crizotinib normalized Ppard and reduced Pparg mRNA expression in diabetic hearts. Crizotinib decreased blood glucose independently of insulin and glucagon. This could be related to changes in regulators of cardiac metabolism such as GLUT4 and PPARs.

Role of glucagon in intestinal hyperemia associated with early experimental diabetes mellitus

1988 ◽  
Vol 255 (5) ◽  
pp. G542-G546
Author(s):  
L. F. Yrle ◽  
J. K. Smith ◽  
J. N. Benoit ◽  
D. N. Granger ◽  
R. J. Korthuis
Keyword(s):  
Diabetes Mellitus ◽  
Blood Flow ◽  
Gastrointestinal Tract ◽  
Experimental Diabetes ◽  
Reference Sample ◽  
Diabetic Rats ◽  
Experimental Diabetes Mellitus ◽  
Blood Flows ◽  
Sample Technique

The role of glucagon as a blood-borne mediator of the intestinal hyperemia associated with experimental diabetes mellitus was assessed in anesthetized fasted (18-24 h) rats 4 wk after the administration of streptozotocin (65 mg/kg body wt) or its vehicle. Selective removal of pancreatic glucagon from the circulation was accomplished by the intravenous administration of a highly specific glucagon antiserum. Blood flow to the gastrointestinal tract and kidneys was measured with radioactive microspheres using the reference sample technique. Blood flows were increased by at least 60% in each segment of the gastrointestinal tract of diabetic animals compared with control rats. Glucagon antiserum had no effect on blood flows in the gastrointestinal tract of control animals. However, the antiserum produced a significant reduction in blood flow to the stomach (26%), duodenum (25%), jejunum (12%), and kidneys (16%) in diabetic rats. There was no change in blood flow to the ileum or colon of diabetic animals with antiserum administration. The results of this study support the hypothesis that glucagon mediates a portion of the hyperemia noted in the stomach, duodenum, and jejunum. However, glucagon does not appear to play a role in the genesis of the hyperemia noted in more distal segments of the gastrointestinal tract (ileum and colon). A possible role for glucagon in the maintenance of renal blood flow in diabetic rats is suggested.

scholarly journals Terminal ileum submucous plexus: Study of the VIP-ergic neurons of diabetic rats treated with ascorbic acid

2002 ◽  
Vol 60 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Jacqueline Nelisis Zanoni ◽  
Luzmarina Hernandes ◽  
Roberto Barbosa Bazotte ◽  
Marcílio Hubner de Miranda Neto
Keyword(s):  
Diabetes Mellitus ◽  
Ascorbic Acid ◽  
Glycated Hemoglobin ◽  
Experimental Diabetes ◽  
Diabetic Rats ◽  
The Other ◽  
Control Group ◽  
Small Reduction ◽  
Experimental Diabetes Mellitus ◽  
Submucous Plexus

The aim of this study was to evaluate the effect of the ascorbic acid (AA) supplementation on the neurons that produce the vasoactive intestinal peptide (VIP) in the submucous plexus of the ileum of rat, four months after the induction of experimental diabetes mellitus with streptozotocin. Three groups of rats were used: C - control, D - diabetic, DA - diabetic receiving AA. We have measured the immunoreactivity and area of 80 cellular bodies of VIP-ergic neurons from each studied group. In the diabetic animals, we have observed hyperphagia, polydipsia, and an increase of glycemia and glycated hemoglobin. The VIP-ergic neurons have presented an increase of their immunoreactivity and the highest profiles when compared to the other groups. In the diabetic animals supplemented with AA it has been observed a small reduction in the glycemia and the water and food intake. We have also noticed smaller immunoreactivity in their VIP-ergic neurons, similar to what we have observed in the control group animals (group C).

scholarly journals Beneficial effects of valencene on altered glycoprotein components in streptozotocin-nicotinamide induced diabetic rats

2019 ◽  
Vol 9 (4-A) ◽  
pp. 191-196
Author(s):  
Ellappan Pari ◽  
Pari Leelavinothan ◽  
Thangasamy Gunaseelan ◽  
Duraisamy Kannan
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Experimental Diabetes ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Glycemic Status ◽  
Experimental Diabetes Mellitus ◽  
Citrate Buffer ◽  
Beneficial Effects

ABSTRACT Objective: To investigate the effect of valencene on dearrangement in glycoprotein levels in the streptozotocin(STZ)-nicotinamide(NA)induced diabetic rats. Materials and Methods: Diabetes was induced in experimental rats by a single intraperitoneal (i.p) injection of STZ (45 mg/kg b.w) dissolved in 0.1 M citrate buffer (pH 4.5) 15 minutes after the i.p injection of NA (110 mg/kg b.w). The levels of glycoproteins were altered in experimental diabetes mellitus. Valencene were administered to diabetic rats intragastrically at 100 & 200mg/kg bw for 30days. The effects of valencene on plasma glucose, insulin, plasma and tissue glycoproteins were studied. Results: Oral administration of valencene (200mg/kg b.w)for 30d, dose dependently improved the glycemic status in STZ-NA induced diabetic rats. The levels of plasma glucose were decreased with significant increase of plasma insulin level. The altered levels of plasma and tissue glycoprotein components were restored to near normal. Conclusions: The results of the present study show the potent beneficial effects of valencene in modifying the levels of glycoprotein components in plasma and tissues of diabetic rats.

Delayed brainstem auditory evoked reponses in experimental diabetes mellitus

1986 ◽  
Vol 100 (8) ◽  
pp. 883-891 ◽  
Author(s):  
N. Buller ◽  
N. Laurian ◽  
I. shvili ◽  
L. Laurian
Keyword(s):  
Diabetes Mellitus ◽  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Evoked Responses ◽  
Experimental Diabetes Mellitus ◽  
Auditory Evoked Responses ◽  
Severe Diabetes ◽  
Neural Transmission ◽  
The Mean ◽  
Central Neuropathy

AbstractThe brainstem auditory evoked responses (BAER) were utilized for the evaluation of central neural transmission in alloxan-induced diabetes in rats. The mean latencies of waves I, III, V and the interpeak latencies III-V and I-V were prolonged in diabetic rats as compared to the same rats before alloxan administration. The incidence of abnormal BAER was more frequent in the group of rats with severe diabetes (82 per cent) than in mildly diabetic animals (42 per cent). Our results may suggest the presence of a central neuropathy in experimental diabetes, which can be detected by the method of BAER.

scholarly journals Potential role of galanine in the treatment of type 2 diabetes mellitus

2020 ◽  
Vol 23 (4) ◽  
pp. 368-373
Author(s):  
Igor Vladimirovich Dobrokhotov ◽  
Oksana M. Veselova ◽  
Roman O. Lyubimov
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Uptake ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Receptor Subtype ◽  
Insulin Synthesis ◽  
Vital Functions ◽  
Insulin Dependent ◽  
Glucose Transporter Glut4 ◽  
G Protein Coupled

The growing incidence of diabetes mellitus requires the optimizing of existing approaches and searching for new ones to treat this disease. It is necessary to study the features of other regulators that play a significant role in the process of glucose uptake by cells, along with the insulin resistance caused by defects in the molecular mechanisms of insulin action. Galanine, a neuropeptide of 29 (30 in humans) amino acids, is involved in a large number of different vital functions, including regulating energy metabolism in the cell. Galanine interacts with three G protein-coupled receptors, GAL1, GAL2, and GAL3, and transmitting signals through several transduction pathways, including cAMP/PKA inhibition (GAL1, GAL3) and phospholipase C (GAL2) stimulation. Agonists and antagonists of galanine receptor subtype GalR1-3 can be used as intended therapeutic targets to treat various human diseases. We accumulated more data that prove the importance of the galanine peptide regulator in the etiology of impaired glucose uptake by insulin-dependent tissues. The review considers such effects of galanine, as inhibition of insulin synthesis, activation of expression and translocation to the plasma cell membrane of the glucose transporter GLUT4, increase of PPAR-g level, and decrease in duodenal hyper-contractility. These data confirm the importance of research to find an effective antidiabetic drug among the synthesized analogs of galanine.

scholarly journals Ethanolic Extract of Folium Sennae Mediates the Glucose Uptake of L6 Cells by GLUT4 and Ca2+

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2934 ◽  
Author(s):  
Ping Zhao ◽  
Qian Ming ◽  
Junying Qiu ◽  
Di Tian ◽  
Jia Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
G Protein ◽  
Glucose Transporter ◽  
Ethanolic Extract ◽  
High Morbidity ◽  
L6 Cells ◽  
Glut4 Expression ◽  
Compound C

In today’s world, diabetes mellitus (DM) is on the rise, especially type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance. T2DM has high morbidity, and therapies with natural products have attracted much attention in the recent past. In this paper, we aimed to study the hypoglycemic effect and the mechanism of an ethanolic extract of Folium Sennae (FSE) on L6 cells. The glucose uptake of L6 cells was investigated using a glucose assay kit. We studied glucose transporter 4 (GLUT4) expression and AMP-activated protein kinase (AMPK), protein kinase B (PKB/Akt), and protein kinase C (PKC) phosphorylation levels using western blot analysis. GLUT4 trafficking and intracellular Ca2+ levels were monitored by laser confocal microscopy in L6 cells stably expressing IRAP-mOrange. GLUT4 fusion with plasma membrane (PM) was observed by myc-GLUT4-mOrange. FSE stimulated glucose uptake; GLUT4 expression and translocation; PM fusion; intracellular Ca2+ elevation; and the phosphorylation of AMPK, Akt, and PKC in L6 cells. GLUT4 translocation was weakened by the AMPK inhibitor compound C, PI3K inhibitor Wortmannin, PKC inhibitor Gö6983, G protein inhibitor PTX/Gallein, and PLC inhibitor U73122. Similarly, in addition to PTX/Gallein and U73122, the IP3R inhibitor 2-APB and a 0 mM Ca2+-EGTA solution partially inhibited the elevation of intracellular Ca2+ levels. BAPTA-AM had a significant inhibitory effect on FSE-mediated GLUT4 activities. In summary, FSE regulates GLUT4 expression and translocation by activating the AMPK, PI3K/Akt, and G protein–PLC–PKC pathways. FSE causes increasing Ca2+ concentration to complete the fusion of GLUT4 vesicles with PM, allowing glucose uptake. Therefore, FSE may be a potential drug for improving T2DM.

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