Reduced glucose clearance as the major determinant of postabsorptive hyperglycemia in diabetic rats

1998 ◽  
Vol 274 (2) ◽  
pp. E257-E264 ◽  
Author(s):  
Jae K. Wi ◽  
Jason K. Kim ◽  
Jang H. Youn
Keyword(s):  
Glucose Transport ◽  
Diabetic Rats ◽  
Type I ◽  
Cellular Mechanisms ◽  
Glucose Levels ◽  
Glucose Clearance ◽  
Dose Study ◽  
High Doses ◽  
Glucose Output ◽  
Intracellular Glucose

The relationships between postabsorptive glucose concentration and hepatic glucose output (HGO) and glucose clearance were studied in rats one day after treatment with various doses of streptozotocin (STZ; 0, 15, 30, 40, 50, or 75 mg/kg; n = 6 per dose; study 1). Glucose fluxes were estimated using a prolonged (6-h) infusion of [3-3H]glucose to ensure complete tracer equilibration at hyperglycemia. Postabsorptive glucose was significantly increased at the high doses of STZ (50 and 75 mg/kg; P < 0.01) and was strongly correlated with glucose clearance across all doses ( r = −0.85, P < 0.001) but less strongly with HGO ( r = 0.46, P < 0.01). In the group treated with 50 mg/kg STZ, postabsorptive glucose was increased twofold compared with the control (i.e., zero dose) group, with no change in HGO and a 45% decrease in glucose clearance, indicating that the hyperglycemia was due to a decrease in glucose clearance. To understand the cellular mechanisms of decreased glucose clearance in STZ diabetic rats, skeletal muscle glucose clearance and intracellular glucose and glucose 6-phosphate (G-6- P) concentrations were determined in normal and STZ (50 mg/kg) diabetic rats at their postabsorptive glucose levels as well as at matched hyperglycemia (12 mM; study 2). Glucose clearance was significantly decreased in soleus ( P< 0.05) muscles of the diabetic rats, and this was associated with significantly decreased intracellular glucose and G-6- P levels at matched hyperglycemia ( P < 0.05), suggestive of decreased glucose transport. In conclusion, postabsorptive hyperglycemia in STZ diabetic rats was largely due to decreased glucose clearance, although increased HGO may also have been a contributing factor at the highest STZ dose. The decrease in postabsorptive glucose clearance in STZ diabetic rats appeared to be associated with an impairment of glucose transport in soleus (type I) muscles.

Chronic hypoglycemia increases brain glucose transport

1986 ◽  
Vol 251 (4) ◽  
pp. E442-E447 ◽  
Author(s):  
A. L. McCall ◽  
L. B. Fixman ◽  
N. Fleming ◽  
K. Tornheim ◽  
W. Chick ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Creatine Phosphate ◽  
Regular Insulin ◽  
Diabetic Rats ◽  
Repeated Injection ◽  
Brain Glucose ◽  
Glucose Levels ◽  
Brain Uptake Index ◽  
Acute Hypoglycemia ◽  
The Brain

Glucose transport into the brain is depressed in chronically hyperglycemic (diabetic) rats. To determine whether hypoglycemia has the opposite effect, brain transport of hexoses and other substrates was examined in chronically and acutely hypoglycemic rats. We produced chronic hypoglycemia by implanting insulin-secreting tumors or insulin-releasing osmotic mini-pumps or by repeated injection of protamine zinc insulin (PZI) and acute hypoglycemia by intravascular injection of regular insulin. Blood-brain barrier (BBB) transport was measured using the brain uptake index (BUI) method. In the three models of chronic hypoglycemia, brain glucose extraction was increased compared with controls. The extraction of deoxyglucose and several other hexoses was also increased by chronic hypoglycemia. Acute hypoglycemia had no effect on brain transport. The transport of other substrates was either not affected or depressed, suggesting increased brain hexose transport is specific. Studies of freeze-blown brain in insulinoma-engrafted rats showed that brain glucose levels were depressed while creatine phosphate, ATP, and glucose 6-phosphate were maintained. Tumor removal led to a reversion of brain glucose transport to control rates but only after 5-25 days. These findings support the view that glucose transport across the BBB is modulated by chronic alterations in the ambient glucose concentration. They also may explain why some patients with chronic hypoglycemia tolerate low blood glucose concentrations.

Insulin binding and glucose metabolism in adipocytes of streptozotocin-diabetic rats.

1978 ◽  
Vol 235 (2) ◽  
pp. E175
Author(s):  
M Kasuga ◽  
Y Akanuma ◽  
Y Iwamoto ◽  
K Kosaka
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transport ◽  
Glucose Oxidation ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Diabetic Rats ◽  
Glucose Transport System ◽  
Streptozotocin Diabetic Rats ◽  
Intracellular Glucose ◽  
Insulin Insensitivity

To investigate the mechanism of the cellular insulin insensitivity of diabetic rats, insulin binding, glucose transport, and glucose oxidation were studied in adipocytes from streptozotocin-diabetic rats. Increased insulin binding was found in cells from diabetic rats, and this was due to an increased number of insulin receptors rather than a change in receptor affinity. Basal and insulin-stimulated glucose oxidation was decreased in adipocytes from diabetic rats when the data are expressed in absolute terms or as percent increased above basal. Although the absolute rate of basal and insulin-stimulated glucose transport was decreased in adipocytes from diabetic rats, the percent increase above basal of insulin-stimulated glucose transport was not decreased. In conclusion, although the cellular insulin insensitivity exists in adipocytes from diabetic rats, the number of insulin receptors was increased, coupling between insulin receptors and the glucose transport system is intact in adipocytes from diabetic rats, and a defect in intracellular glucose metabolism rather than glucose transport plays a major role in the insulin insensitivity of adipocytes from diabetic rats.

Mechanisms of postabsorptive hyperglycemia in streptozotocin diabetic rats

1996 ◽  
Vol 270 (5) ◽  
pp. E752-E758 ◽  
Author(s):  
J. K. Wi ◽  
J. K. Kim ◽  
J. H. Youn
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Diabetic Rats ◽  
Normal Rate ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Clearance ◽  
Streptozotocin Diabetic Rats ◽  
Acute Changes ◽  
Glucose Output

Postabsorptive hepatic glucose output (HGO) was estimated in normal (n = 9) and streptozotocin (STZ) diabetic rats after a 6-h [3-3H]glucose infusion. In diabetic rats, HGO was estimated at ambient (n = 12) or normal (achieved via phlorizin infusion; n = 9) glucose concentrations. HGO was not statistically different between normal and diabetic rats (63 +/- 3 vs. 77 +/- 10 mumol.kg-1.min-1; P> 0.05). HGO was also normal in diabetic rats even when plasma glucose was normalized with phlorizin infusion (71 +/- 5 vs. 63 +/- 3 mumol.kg-1.min-1; P> 0.05). In contrast, peripheral glucose uptake, when estimated at matched euglycemia, was lower by approximately 25% in diabetic than in normal rate (46 +/- 6 vs. 62 +/- 3 mumol.kg-1.min-1; P < 0.01). In addition, acute changes in plasma glucose concentrations did not have significant effects on HGO or peripheral glucose uptake in diabetic rats (P> 0.05), resulting in markedly decreased glucose clearance at ambient hyperglycemia (P < 0.001). In conclusion, postabsorptive HGO was not elevated in a majority (17 of 21) of STZ diabetic rats with severe hyperglycemia and therefore was not responsible for postabsorptive hyperglycemia. Our data suggest that an impairment in the ability of glucose to regulate peripheral glucose uptake or HGO develops in STZ diabetes and contributes to postabsorptive hyperglycemia.

scholarly journals Antiobesity and Hypoglycaemic Effects of Aqueous Extract ofIbervillea sonoraein Mice Fed a High-Fat Diet with Fructose

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Fabiola Rivera-Ramírez ◽  
Gerardo N. Escalona-Cardoso ◽  
Leticia Garduño-Siciliano ◽  
Carlos Galaviz-Hernández ◽  
Norma Paniagua-Castro
Keyword(s):  
Aqueous Extract ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
High Fat ◽  
Simultaneous Treatment ◽  
Glucose Levels ◽  
Hepatic Oxidation ◽  
Calorie Diet ◽  
High Doses

Obesity, type II diabetes, and hyperlipidaemia, which frequently coexist and are strongly associated with oxidative stress, increase the risk of cardiovascular disease. An increase in carbohydrate intake, especially of fructose, and a high-fat diet are both factors that contribute to the development of these metabolic disorders. In recent studies carried out in diabetic rats, authors reported thatIbervillea sonoraehad hypoglycaemic activity; saponins and monoglycerides present in the plant could be responsible for the effects observed. In the present study, we determined the effects of an aqueousI. sonoraeextract on a murine model of obesity and hyperglycaemia, induced by a high-calorie diet, and the relationship of these effects with hepatic oxidation. A high-fat diet over a period of 8 weeks induced weight gain in the mice and increased triglycerides and blood glucose levels. Simultaneous treatment withI. sonoraeaqueous extracts, at doses of 100, 200, and 400 mg/kg, decreased triglycerides and glycaemia levels, prevented an increase in body weight in a dose-dependent manner, and decreased hepatic lipid oxidation at a dose of 200 mg/kg. These data suggest that the aqueous extract fromI. sonoraeroot prevents obesity, dyslipidaemia, and hyperglycaemia induced by a hypercaloric diet; however, high doses may induce toxicity.

Vildagliptin/pioglitazone combination improved the overall glycemic control in type I diabetic rats

2018 ◽  
Vol 96 (8) ◽  
pp. 710-718 ◽  
Author(s):  
Amir Mohamed Abdelhamid ◽  
Rania Ramadan Abdelaziz ◽  
Hatem Abdelrahman Ali Salem
Keyword(s):  
Glycemic Control ◽  
Type I Diabetes ◽  
Serum Insulin ◽  
Immunohistochemical Analysis ◽  
Diabetic Rats ◽  
Suboptimal Control ◽  
Type I ◽  
Β Cells ◽  
Treatment Regimens ◽  
Glucose Levels

Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of vildagliptin (Vilda) alone or in combination with pioglitazone (Pio), as treatment regimens for TID using streptozotocin (STZ)-induced TID model in rats. Daily oral administration of Vilda (5 mg/kg) alone or in combination with Pio (20 mg/kg) for 7 weeks significantly reduced blood glucose levels and HbA1c. It increased serum insulin levels and decreased serum glucagon. It also showed a strong antioxidant activity. Immunohistochemical analysis showed a marked improvement in β-cells in treated groups when compared with the diabetic group, which appeared in the normal cellular and architecture restoration of β-cells in the islets of Langerhans. Vilda alone or in combination with Pio has the ability to improve the overall glycemic control in type I diabetic rats and may be considered a hopeful and effective remedy for TID.

Early diabetes-induced changes in rat jejunal glucose transport and the response to insulin

1997 ◽  
Vol 154 (1) ◽  
pp. 19-25 ◽  
Author(s):  
P A Sharp ◽  
S Boyer ◽  
S K S Srai ◽  
S A Baldwin ◽  
E S Debnam
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Driving Force ◽  
Insulin Treatment ◽  
Basolateral Membrane ◽  
Sugar Transport ◽  
Diabetic Rats ◽  
Na Channel ◽  
Early Diabetes ◽  
Glucose Levels

Abstract The effects of 1 day of streptozotocin-induced diabetes in rats on glucose transport across the brush border membrane (BBM) and basolateral membrane (BLM) prepared from jejunal enterocytes has been studied. The effects on glucose transport of treatment of diabetic animals with insulin to reduce to normal the elevated blood glucose levels has also been assessed. The maximum capacity (Vmax) for SGLT1-mediated glucose uptake by BBM vesicles was unaffected by diabetes or insulin treatment of diabetic rats. In contrast, Vmax for BLM glucose uptake was increased by 206% in diabetes, a response that could not be reversed by treatment with insulin. Western blotting of BBM for SGLT1 protein revealed a single band with a molecular weight of 73 kDa and the intensity of this band was unaffected by diabetes. However, an increased level of GLUT2 was noted in diabetic BLM and this was not a consequence of changes in glycaemic or insulin status. Diabetes hyperpolarised the BBM, implying an increased driving force for Na+-sugar co-transport but insulin treatment only partially reversed this enhanced potential difference. Benzamil (2 μm), an epithelial Na+ channel blocker, hyperpolarised the BBM of control but not diabetic enterocytes, implying that a reduced Na+ permeability was responsible for the diabetic hyperpolarisation. It was concluded that in early diabetes, before the onset of hyperphagia, a greater driving force for Na+-dependent BBM sugar transport together with increased GLUT2 activity at the BLM promotes sugar movement across the enterocyte. Possible triggers for the transport responses are discussed. Journal of Endocrinology (1997) 154, 19–25

Effects of D-glucose and β-hydroxybutyric acid on the in vitro development of (pre)chondrocytes from embryos of normal and diabetic rats

1990 ◽  
Vol 122 (4) ◽  
pp. 487-498 ◽  
Author(s):  
Johan Styrud ◽  
Ulf J. Eriksson
Keyword(s):  
Thymidine Incorporation ◽  
Diabetic Rats ◽  
Limb Bud ◽  
Female Rats ◽  
Hydroxybutyric Acid ◽  
Cellular Mechanisms ◽  
Mandibular Arch ◽  
Glucose Levels ◽  
Selective Sensitivity

Abstract. In order to elucidate cellular mechanisms causing skeletal malformations in offspring of diabetic rats we studied the incorporation of thymidine and sulphate into embryonic (pre)chondrocytes exposed to increased levels of D-glucose and β-hydroxybutyric acid for six days in vitro. The (pre)chondrocytes were prepared from embryos of normal or diabetic rats of a malformation-prone strain or from embryos of normal rats of a non-malformation-prone strain. Diabetic female rats of the former strain are known to produce a high proportion of offspring with mandibular and lumbosacral malformations. Increased β-hydroxybutyric acid caused decreased thymidine incorporation in all types of chondrocytes, and decreased sulphate incorporation in limb bud cells from embryos of normal rats from both strains. Elevated D-glucose levels yielded a slight decrease in thymidine incorporation in mandibular arch cells from embryos of normal rats of the malformation-prone strain, and a marked decrease of both sulphate and thymidine incorporation in mandibular arch cells from embryos of diabetic rats of this strain. The observations suggest that elevated levels of D-glucose or β-hydroxybutyric acid are able to inhibit the differentiation and growth of (pre)chondrocytes and illustrate a selective sensitivity of mandibular arch (pre)chondrocytes to a diabetic environment. The data are compatible with the view that both D-glucose and β-hydroxybutyric acid may cause aberrations in the development of rat mandibular arch chondrocytes, suggesting a role for these compounds in diabetic teratogenesis.

Insulin-sparing effect of hydroxychloroquine in diabetic rats is concentration dependent

1999 ◽  
Vol 77 (2) ◽  
pp. 118-123 ◽  
Author(s):  
Jaber Emami ◽  
Hertzel C Gerstein ◽  
Franco M Pasutto ◽  
Fakhreddin Jamali
Keyword(s):  
Therapeutic Potential ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Type I ◽  
Time Curve ◽  
Insulin Metabolism ◽  
Glucose Levels ◽  
Percent Change ◽  
Glucose Challenge

To study the effect of hydroxychloroquine (HCQ) on glucose and insulin homeostasis, healthy rats were dosed with160 mg·kg-1·day-1 of HCQ orally, and streptozocin-induced diabetic rats received 80, 120, and 160 mg·kg-1·day-1 of HCQ, while controls received normal saline. Ten days after treatment with HCQ, healthy animals were challenged intravenously with insulin or glucose, while diabetic rats were given only an i.v. injection of insulin. In healthy rats, the areas within and under the glucose concentration - time curve following insulin and glucose challenge were estimated. In diabetic animals, the areas under the curve for both the percent change in serum glucose from baseline (AUG) and the percent change in serum insulin from baseline (AUI) were used as pharmacodynamic end points. In healthy rats, HCQ did not influence fasting serum glucose concentrations or glycemic profiles following i.v. administration of glucose or insulin. In diabetic rats, AUG and AUI were increased dependent on blood HCQ concentrations. The normal homeostatic mechanisms responsible for insulin-glucose regulation may compensate for possible HCQ-induced reduction of insulin metabolism in healthy rats. The HCQ dose- or concentration-effect relationships for glucose and insulin were linear over the range of HCQ concentrations tested. It is concluded that HCQ significantly elevated insulin blood concentration resulting in reduced glucose levels in a concentration-dependent fashion in diabetic rats. HCQ may have therapeutic potential in the treatment of type I and type II diabetes.Key words: hydroxychloroquine, enantiomers, insulin, glucose, diabetes, pharmacokinetics.

Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones

2019 ◽  
Vol 89 (1-2) ◽  
pp. 45-54
Author(s):  
Akemi Suzuki ◽  
André Manoel Correia-Santos ◽  
Gabriela Câmara Vicente ◽  
Luiz Guillermo Coca Velarde ◽  
Gilson Teles Boaventura
Keyword(s):  
Thyroid Hormones ◽  
High Fat Diet ◽  
Female Offspring ◽  
Flaxseed Oil ◽  
Diabetic Rats ◽  
High Fat ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Flaxseed Flour ◽  
Maternal Consumption

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.

Antidiabetic effect of Psychotria malayana Jack in induced type 1 diabetic rat

MEDISAINS ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 19
Author(s):  
Fairuz Fairuz ◽  
Hasna Dewi ◽  
Humaryanto Humaryanto
Keyword(s):  
Blood Glucose ◽  
Side Effects ◽  
Type I Diabetes ◽  
Langerhans Cell ◽  
Diabetic Rat ◽  
Type I ◽  
Antidiabetic Effect ◽  
Glucose Levels ◽  
Blood Glucose Levels

Background: Therapies for hyperglycemic treatment, including insulin and oral diabetes medications, have been confirmed to cause several side effects. Thus, finding new drugs with fewer side effects is of high importance. Salung leaf herb (Psychotria malayana Jack) reported used in traditional societies as a treatment for diabetes. However, the scientific proof of this plant for diabetes treatment is still lacking.Objective: To evaluate the antidiabetic effect of the P. malayana jack in induced type 1 diabetic rats by assessing blood glucose level and pancreatic cells in white rats.Methods: Alloxan used to induce type I diabetes. Rats randomly divided into six groups. A Group P1 received 250 mg/kg BW; group P2 received 500 mg/kg BW, group P3 received 1000 mg/kg BW. While group 4 basal received no treatment, group 5 received distilled water as a negative control, and group 6 received glibenclamide as a positive control. Medications are given for six days. Glucose levels were measured, and observation of pancreatic Langerhans cell damages.Results:  A decrease in blood glucose levels observed in all treatment groups. The most significant reduction (49.76%; 1000 mg/kg BW) occurred in the P3 group. Morphological features of pancreatic Langerhans cell damage were slightly high in the P1 group.Conclusion: P. malayana Jack can consider having an antidiabetic effect in a type 1 diabetic rat by reducing blood glucose levels.

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