scholarly journals Adrenalectomy improves glycemic responses in congenic obese LA/Ntul//-cp RATS

2021 ◽  
Vol 9 (3) ◽  
pp. 61-67
Author(s):  
Orien L Tulp ◽  
Aftab R Awan ◽  
George P Einstein
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Chow Diet ◽  
Peripheral Tissues ◽  
Treatment Groups ◽  
Purina Chow ◽  
Glucose Ratio ◽  
Obese Rats ◽  
Early Expression ◽  
Obese Phenotype

To determine the effects of adrenalectomy on typical insulin-mediated glycemic responses in male obese rats, groups (n=6 -12 rats/phenotype) of normally reared congenic lean and obese animals were fed a Purina chow diet from 6 to 9 weeks of age, and the Chow diet plus a highly palatable cafeteria diet from 9 to 12 weeks of age. The congenic LA/Ntul//-cp rat strain is noted for its longevity and early expression of the obese trait but remains non-diabetic throughout much if not all of its normal lifespan. Subgroups of obese animals were subjected to bilateral adrenalectomy (ADX) at 6 weeks of age to remove glucocorticoid contributions to glycemic parameters. Measures of weight gain (WG )and of glucose tolerance (OGT) were obtained in the three treatment groups at 6, 9 and 12 weeks of age. WG on ADX-obese rats was similar to that of their lean littermates at 6 and 9 weeks of age on the chow diet but increased to twice that observed in their lean littermates from 9 to 12 weeks of age. OGT responses after 30 to 60 minutes and the area under the OGT curve were impaired but not diabetic in obese animals at all ages compared to lean littermates and returned toward those of normally lean rats after ADX. The Insulin to glucose ratio (I:G) was also consistent with insulin resistance in obese but not in ADX-obese or lean rats at 12 weeks of age. In conclusion, ADX resulted in normalization of OGT and glycemic parameters in the obese phenotype at 9 and 12 weeks of age. These results are consistent with normalization of typical insulin-mediated components of glycemic parameters and glucose uptake in peripheral tissues following adrenalectomy of congenic obese rats. The results further suggest that the counterregulatory effects of insulin and glucocorticoid hormones may be contributory to the impaired glycemic responses in the obese phenotype of the LA/N//-cp (corpulent) rat and are consistent with a receptor-mediated element in the development of insulin resistance and glucose uptake in peripheral tissues commonly associated with the early development of obesity in this strain.

scholarly journals Peripheral insulin resistance in ILK-depleted mice by reduction of GLUT4 expression

2017 ◽  
Vol 234 (2) ◽  
pp. 115-128 ◽  
Author(s):  
Marco Hatem-Vaquero ◽  
Mercedes Griera ◽  
Andrea García-Jerez ◽  
Alicia Luengo ◽  
Julia Álvarez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Chow Diet ◽  
Peripheral Tissues ◽  
Akt Phosphorylation ◽  
Glut4 Expression

The development of insulin resistance is characterized by the impairment of glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix changes are induced when the metabolic dysregulation is sustained. The present work was devoted to analyze the possible link between the extracellular-to-intracellular mediator integrin-linked kinase (ILK) and the peripheral tissue modification that leads to glucose homeostasis impairment. Mice with general depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited increased glycemia and insulinemia concurrently with a reduction of the expression and membrane presence of GLUT4 in the insulin-sensitive peripheral tissues compared with their wild-type littermates (WT). Tolerance tests and insulin sensitivity indexes confirmed the insulin resistance in cKD-ILK, suggesting a similar stage to prediabetes in humans. Under randomly fed conditions, no differences between cKD-ILK and WT were observed in the expression of insulin receptor (IR-B) and its substrate IRS-1 expressions. The IR-B isoform phosphorylated at tyrosines 1150/1151 was increased, but the AKT phosphorylation in serine 473 was reduced in cKD-ILK tissues. Similarly, ILK-blocked myotubes reduced their GLUT4 promoter activity and GLUT4 expression levels. On the other hand, the glucose uptake capacity in response to exogenous insulin was impaired when ILK was blocked in vivo and in vitro, although IR/IRS/AKT phosphorylation states were increased but not different between groups. We conclude that ILK depletion modifies the transcription of GLUT4, which results in reduced peripheral insulin sensitivity and glucose uptake, suggesting ILK as a molecular target and a prognostic biomarker of insulin resistance.

scholarly journals Loss of CTRP5 improves insulin action and hepatic steatosis

2016 ◽  
Vol 310 (11) ◽  
pp. E1036-E1052 ◽  
Author(s):  
Xia Lei ◽  
Susana Rodriguez ◽  
Pia S. Petersen ◽  
Marcus M. Seldin ◽  
Caitlyn E. Bowman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Insulin Action ◽  
Subcutaneous Fat ◽  
Physiological Role ◽  
Negative Regulator ◽  
Chow Diet ◽  
High Fat ◽  
Peripheral Tissues ◽  
Obesity And Diabetes

The gene that encodes C1q/TNF-related protein 5 (CTRP5), a secreted protein of the C1q family, is mutated in individuals with late-onset retinal degeneration. CTRP5 is widely expressed outside the eye and also circulates in plasma. Its physiological role in peripheral tissues, however, has yet to be elucidated. Here, we show that Ctrp5 expression is modulated by fasting and refeeding, and by different diets, in mice. Adipose expression of CTRP5 was markedly upregulated in obese and diabetic humans and in genetic and dietary models of obesity in rodents. Furthermore, human CTRP5 expression in the subcutaneous fat depot positively correlated with BMI. A genetic loss-of-function mouse model was used to address the metabolic function of CTRP5 in vivo. On a standard chow diet, CTRP5-deficient mice had reduced fasting insulin but were otherwise comparable with wild-type littermate controls in body weight and adiposity. However, when fed a high-fat diet, CTRP5-deficient animals had attenuated hepatic steatosis and improved insulin action. Loss of CTRP5 also improved the capacity of chow-fed aged mice to respond to subsequent high-fat feeding, as evidenced by decreased insulin resistance. In cultured adipocytes and myotubes, recombinant CTRP5 treatment attenuated insulin-stimulated Akt phosphorylation. Our results provide the first genetic and physiological evidence for CTRP5 as a negative regulator of glucose metabolism and insulin sensitivity. Inhibition of CTRP5 action may result in the alleviation of insulin resistance associated with obesity and diabetes.

scholarly journals Exercise enhancement of hepatic insulin-sensitising substance-mediated glucose uptake in diet-induced prediabetic rats

2012 ◽  
Vol 109 (5) ◽  
pp. 844-852 ◽  
Author(s):  
Kawshik K. Chowdhury ◽  
Dallas J. Legare ◽  
W. Wayne Lautt
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Exercise Intervention ◽  
Sucrose Solution ◽  
Voluntary Exercise ◽  
Glucose Disposal ◽  
Peripheral Tissues ◽  
Induce Insulin Resistance ◽  
Running Wheel Exercise

The sensitisation of insulin action in response to a meal (i.e. meal-induced insulin sensitisation, MIS) represents one of the major means of increased glucose disposal in peripheral tissues during the postprandial state. MIS occurs when the release of hepatic insulin-sensitising substance (HISS) stimulates skeletal muscle glucose uptake. Our previous study had demonstrated that the HISS pathway is impaired in age-associated insulin resistance, and in the rats which were part of that study, voluntary exercise improved the response to insulin by restoring HISS action. The present study tests the hypothesis that voluntary exercise would reverse insulin resistance in diet-induced models of insulin resistance, and that the benefits are attributed through the improvement in HISS action. In this study, two experimental diets, a high-fat diet (for 4 weeks) and 35 % sucrose solution (for 9 and 16 weeks), were used to induce insulin resistance in rats. These rats were assigned to the exercise/no-exercise intervention. The effect of 7 d voluntary running-wheel exercise was determined by measuring insulin- and HISS action in the exercised rats and comparing them with the non-exercised controls. Voluntary exercise reversed insulin resistance, caused by dietary manipulation, through restoration of the HISS action. The direct insulin action was not changed by either diet or exercise. The metabolic improvements and reduced adiposity correlated with the extent of reversal of HISS action induced by exercise. Exercise improves insulin sensitivity in diet-induced insulin resistance primarily by restoration of HISS-mediated glucose uptake.

scholarly journals Trilobatin Ameliorates Insulin Resistance through IRS-AKT-GLUT4 Signaling Pathway in C2C12 Myotubes and ob/ob Mice

2020 ◽  
Author(s):  
Min Liu ◽  
Lujing Wang ◽  
Xigan Li ◽  
Yucui Wu ◽  
Fei Yin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Fasting Blood Glucose ◽  
C2c12 Myotubes ◽  
Peripheral Tissues ◽  
Resistance Protein ◽  
Type 2 Diabetic

Abstract Background: Trilobatin, a natural compound, has been found to exhibit anti-diabetic properties in high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic mice. But up to now no research has been reported on the effect of trilobatin on insulin resistance in peripheral tissues. Herein, we determined the effects of trilobatin on insulin resistance in palmitate-treated C2C12 myotubes and ob/ob mice.Methods: 8-10 weeks of male ob/ob mice and same background C57BL/6 mice were used to evaluate the role of trilobatin on insulin resistance; Protein expression and phosphorylation were measured by western blot; Glucose uptake was determined a fluorescent test.Results: treatment with trilobatin prevented palmitate-induced insulin resistance by enhancing glucose uptake and the phosphorylation of IRS1 and AKT, recovered the translocation of GLUT4 from cytoplasm to membrane, but preincubation with LY294002, an inhibitor of PI3K, blocked the effects of trilobatin on glucose uptake and the distribution of GLUT4 in C2C12 myotubes. Furthermore, administration with trilobatin for 4 weeks significantly improved insulin resistance by decreasing fasting blood glucose and insulin in serum, enhancing the phosphorylation of IRS1 and AKT, and recovering the expression and translocation of GLUT4 in ob/ob mice.Conclusions: IRS-AKT-GLUT4 signaling pathway might be involved in trilobatin ameliorating insulin resistance in skeletal muscle of obese animal models.

scholarly journals EFFECTS OF PHYSICAL EXERCISES ON TRIACYLGLYCEROL LEVEL IN SKELETAL MUSCLES IN DIETARY-INDUCED OBESE RATS

2014 ◽  
Vol 13 (1) ◽  
pp. 92-97
Author(s):  
I. Yu. Yakimovich ◽  
D. A. Borodin ◽  
I. K. Podrezov ◽  
V. V. Ivanov ◽  
V. N. Vasiliyev ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscles ◽  
High Energy ◽  
Standard Diet ◽  
Peripheral Tissues ◽  
Physical Exercises ◽  
Obese Rats ◽  
High Insulin ◽  
Triacylglycerol Level ◽  
Aerobic And Anaerobic

The accumulation of triacylglycerol in peripheral tissues is one of mechanisms of insulin resistance. This paper presents the investigation of the influence of aerobic and anaerobic physical exercises on triacylglycerol level in skeletal muscles and on insulin resistance in dietary-induced obese rats. It is estimated that a high-energy (HE) diet causes the accumulation of triacylglycerols in skeletal muscles that leads to high resistance to insulin. Aerobic and anaerobic physical exercises reduce the level of triacylglycerols in skeletal  muscles  and  raise  sensitivity to  insulin  in  obese  rats.  Physical  exercises  raise  the  level  of triacylglycerols in skeletal muscles in standard-diet rats that probably is the adaptation to high energy expenditure, but does not lead to high insulin resistance.

Evidence of a defect in insulin-receptor recycling in adipocytes from older rats

1988 ◽  
Vol 254 (1) ◽  
pp. E39-E44 ◽  
Author(s):  
V. Trischitta ◽  
G. M. Reaven
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Insulin Binding ◽  
Receptor Complex ◽  
Receptor Recycling ◽  
Insulin Effect ◽  
Insulin Resistant ◽  
Obese Rats ◽  
Old Rats

Although insulin-stimulated glucose uptake is known to be decreased in adipocytes isolated from old obese rats, the cause of this defect is not totally understood. In the present study, we examined the possibility that insulin resistance is associated with defects in the intracellular processing of the insulin-receptor complex. Adipocytes were isolated from control (2-mo-old rats) and obese, insulin-resistant rats (12-mo-old rats), and the following measurements were made: 1) insulin-stimulated glucose uptake; 2) insulin binding; 3) insulin-receptor internalization and recycling; 4) accumulation of insulin within the cell; and 5) rate of loss of insulin from the cell. The results indicated that maximal insulin-stimulated glucose uptake was significantly reduced in adipocytes from obese, insulin-resistant rats (increase over basal value was 500 +/- 53% in obese rats and 1,200 +/- 96 in control rats, P less than 0.01). 125I-insulin (A14) binding (cell-associated radioactivity) and the internalization of the hormone-receptor complex were not different in the two groups of animals studied. In contrast, insulin-receptor recycling was significantly decreased in adipocytes from obese rats (72.0 +/- 6.1 vs. 93.6 +/- 2.6%, P less than 0.01). In addition, loss of intracellular radioactivity was significantly prolonged in insulin-resistant rats (t1/2 = 12.05 +/- 0.9 vs. 9.4 +/- 0.3 min, P less than 0.05). Thus adipocytes isolated from the older rats were resistant to the insulin effect on glucose uptake, and this defect was not associated with a reduction in insulin binding. However, there was a decrease in insulin receptor recycling, and this phenomenon may be related to the insulin resistance present in these cells.

Energy balance and diabetes. The effects of cold exposure, exercise training, and diet composition on glucose tolerance and glucose metabolism in rat peripheral tissues

1989 ◽  
Vol 67 (4) ◽  
pp. 382-393 ◽  
Author(s):  
Ludwik Jan Bukowiecki
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Energy Expenditure ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Cold Exposure ◽  
High Fat ◽  
Peripheral Tissues ◽  
Brown Adipose

The effects of cold exposure, exercise training, and diet (high fat versus high carbohydrate) on glucose tolerance and glucose metabolism in rat peripheral tissues will be briefly reviewed. Stimulation of energy expenditure by cold exposure (4 °C) or exercise training generally leads to decreased plasma insulin levels and to an improvement in glucose tolerance, suggesting that insulin action on peripheral tissues is increased when energy expenditure is stimulated. On the contrary, feeding high-fat diets to sedentary rats living in the warm (25 °C) induces hyperinsulinemia and insulin resistance resulting in a marked deterioration of glucose tolerance. Nevertheless, cold exposure reverses the diabetogenic effects of high-fat feeding, demonstrating that nutrition-induced insulin resistance is amplified in sedentary animals living at temperatures close to thermoneutrality. Radioactive tracer studies of 2-deoxyglucose uptake in peripheral tissues revealed that cold exposure synergistically potentiates the effects of insulin on glucose uptake in skeletal muscles as well as in white and brown adipose tissues. However, more recent data showed that cold exposure improves glucose tolerance and stimulates glucose uptake in starved animals (ie., in the virtual absence of circulating insulin) nearly by the same order of magnitude as in fed animals. It is therefore concluded that cold exposure, and possibly also exercise, improve glucose tolerance and stimulate glucose uptake in peripheral tissues primarily by enhancing glucose oxidation via insulin-independent pathways, and secondarily by increasing the responsiveness of peripheral tissues to insulin.Key words: insulin, brown adipose tissue, skeletal muscle, 2-deoxyglucose, diabetes.

Insulin-mediated potassium uptake is normal in uremic and healthy subjects

1984 ◽  
Vol 246 (2) ◽  
pp. E174-E180 ◽  
Author(s):  
A. Alvestrand ◽  
J. Wahren ◽  
D. Smith ◽  
R. A. DeFronzo
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Healthy Subjects ◽  
Potassium Concentration ◽  
Plasma Potassium ◽  
Potassium Uptake ◽  
Peripheral Tissues ◽  
Fluid Compartment ◽  
Venous Catheterization ◽  
The Mean

We examined the ability of physiological hyperinsulinemia to enhance potassium and glucose uptake by splanchnic and peripheral tissues in 12 chronically uremic subjects by using the euglycemic insulin clamp technique in combination with hepatic and femoral venous catheterization. In control subjects, the decline in plasma potassium concentration averaged 0.95 +/- 0.05 meq/liter. Splanchnic (67 +/- 10.3 mu eq/min) and leg (22.2 +/- 1.4 mu eq/min) potassium uptake accounted for 43 and 59%, respectively, of the total amount of potassium that was translocated from the extracellular to intracellular fluid compartment. In uremic individuals, the decline in plasma potassium concentration (0.98 +/- 0.10) was similar to controls. Likewise, the mean splanchnic (66.6 +/- 6.1 mu eq/min) and leg (22.4 +/- 1.6 mu eq/min) potassium uptakes were similar to controls. These results indicate that insulin-mediated potassium uptake is not altered by uremia. In contrast, insulin-mediated glucose uptake is markedly impaired. These observations suggest that the various actions of insulin can be differentially impaired by uremia and that steps distal to the insulin receptor must be responsible for the insulin resistance.

Exercise and diet reduce muscle insulin resistance in obese Zucker rat

1986 ◽  
Vol 251 (3) ◽  
pp. E299-E305 ◽  
Author(s):  
J. L. Ivy ◽  
W. M. Sherman ◽  
C. L. Cutler ◽  
A. L. Katz
Keyword(s):  
Insulin Resistance ◽  
Exercise Training ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
High Carbohydrate Diet ◽  
Carbohydrate Diet ◽  
Muscle Insulin Resistance ◽  
High Carbohydrate ◽  
Obese Zucker Rat ◽  
Obese Rats

Two treatments that increase skeletal muscle insulin action are exercise training and high-carbohydrate diet. The purpose of the present study was to determine whether exercise training and a diet high in carbohydrates could function synergistically to reduce the muscle insulin resistance in the obese Zucker rat. Obese rats 4 wk of age were randomly assigned to an exercise or sedentary group. Each group was subdivided by diet with one-half of the rats fed a high-carbohydrate diet and one-half fed a high-fat diet. Lean Zucker rats fed the high-fat diet were used as controls. Muscle insulin resistance was assessed during hindlimb perfusion with a submaximally stimulating concentration of insulin. Exercise training and the high-carbohydrate diet increased the rate of muscle glucose uptake in the obese rat by 46 and 53%, respectively. More importantly, the combined effect of exercise training and high-carbohydrate diet was greater than the sum of their individual effects. Glycogen synthesis paralleled glucose uptake and was the major pathway for intracellular glucose disposal. Muscle glucose uptake for exercise-trained, high-carbohydrate fed obese rats was comparable with that of lean controls. It is concluded that exercise training and the high-carbohydrate diet functioned synergistically to reduce the muscle insulin resistance in the obese rat.

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