scholarly journals Differential effects of hypercaloric choice diets on insulin sensitivity in rats

2017 ◽  
Vol 232 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Charlene Diepenbroek ◽  
Leslie Eggels ◽  
Mariëtte T Ackermans ◽  
Eric Fliers ◽  
Andries Kalsbeek ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Intolerance ◽  
Free Choice ◽  
Saturated Fat ◽  
High Fat ◽  
Short Term ◽  
Sugar Water ◽  
Hepatic Insulin Sensitivity ◽  
Peripheral Insulin Sensitivity ◽  
High Sugar

We showed previously that rats on a free-choice high-fat, high-sugar (fcHFHS) diet become rapidly obese and develop glucose intolerance within a week. Interestingly, neither rats on a free-choice high-fat diet (fcHF), although equally obese and hyperphagic, nor rats on a free-choice high-sugar (fcHS) diet consuming more sugar water, develop glucose intolerance. Here, we investigate whether changes in insulin sensitivity contribute to the observed glucose intolerance and whether this is related to consumption of saturated fat and/or sugar water. Rats received either a fcHFHS, fcHF, fcHS or chow diet for one week. We performed a hyperinsulinemic–euglycemic clamp with stable isotope dilution to measure endogenous glucose production (EGP; hepatic insulin sensitivity) and glucose disappearance (Rd; peripheral insulin sensitivity). Rats on all free-choice diets were hyperphagic, but only fcHFHS-fed rats showed significantly increased adiposity. EGP suppression by hyperinsulinemia in fcHF-fed and fcHFHS-fed rats was significantly decreased compared with chow-fed rats. One week fcHFHS diet also significantly decreased Rd. Neither EGP suppression nor Rd was affected in fcHS-fed rats. Our results imply that, short-term fat feeding impaired hepatic insulin sensitivity, whereas short-term consumption of both saturated fat and sugar water impaired hepatic and peripheral insulin sensitivity. The latter likely contributed to glucose intolerance observed previously. In contrast, overconsumption of only sugar water affected insulin sensitivity slightly, but not significantly, in spite of similar adiposity as fcHF-fed rats and higher sugar intake compared with fcHFHS-fed rats. These data imply that the palatable component consumed plays a role in the development of site-specific insulin sensitivity.

A free-choice high-fat high-sugar diet induces glucose intolerance and insulin unresponsiveness to a glucose load not explained by obesity

2010 ◽  
Vol 35 (4) ◽  
pp. 595-604 ◽  
Author(s):  
S E la Fleur ◽  
M C M Luijendijk ◽  
A J van Rozen ◽  
A Kalsbeek ◽  
R A H Adan
Keyword(s):  
Glucose Intolerance ◽  
Free Choice ◽  
Glucose Load ◽  
High Fat ◽  
High Sugar

The snacking rat as model of human obesity: effects of a free-choice high-fat high-sugar diet on meal patterns

2013 ◽  
Vol 38 (5) ◽  
pp. 643-649 ◽  
Author(s):  
S E la Fleur ◽  
M C M Luijendijk ◽  
E M van der Zwaal ◽  
M A D Brans ◽  
R A H Adan
Keyword(s):  
Free Choice ◽  
High Fat ◽  
Human Obesity ◽  
Meal Patterns ◽  
High Sugar

scholarly journals OR28-6 Short-Term Mifepristone Treatment Improves Hepatic and Adipose Tissue Insulin Sensitivity in Overweight and Obese Subjects with Glucose Intolerance

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Shivraj Grewal ◽  
Susmeeta Sharma ◽  
Raven McGlotten ◽  
Ranganath Muniyappa ◽  
Lynnette Nieman
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Intolerance ◽  
Short Term ◽  
Obese Subjects

scholarly journals Short-term strength training reduces gluconeogenesis and NAFLD in obese mice

2019 ◽  
Vol 241 (1) ◽  
pp. 59-70 ◽  
Author(s):  
Rodrigo Martins Pereira ◽  
Kellen Cristina da Cruz Rodrigues ◽  
Chadi Pellegrini Anaruma ◽  
Marcella Ramos Sant’Ana ◽  
Thaís Dantis Pereira de Campos ◽  
...  
Keyword(s):  
Weight Loss ◽  
Insulin Sensitivity ◽  
Strength Training ◽  
Term Strength ◽  
Obese Mice ◽  
Short Term ◽  
Fat Accumulation ◽  
Hepatic Insulin Sensitivity ◽  
Short Term Strength ◽  
Hepatic Fat

Non-alcoholic fatty liver disease (NAFLD) has a positive correlation with obesity, insulin resistance and type 2 diabetes mellitus (T2D). The aerobic training is an important tool in combating NAFLD. However, no studies have demonstrated the molecular effects of short-term strength training on the accumulation of hepatic fat in obese mice. This study aimed to investigate the effects of short-term strength training on the mechanisms of oxidation and lipid synthesis in the liver of obese mice. The short duration protocol was used to avoid changing the amount of adipose tissue. Swiss mice were separated into three groups: lean control (CTL), sedentary obese (OB) and strength training obese (STO). The obese groups were fed a high-fat diet (HFD) and the STO group performed the strength training protocol 1 session/day for 15 days. The short-term strength training reduced hepatic fat accumulation, increasing hepatic insulin sensitivity and controlling hepatic glucose production. The obese animals increased the mRNA of lipogenic genes Fasn and Scd1 and reduced the oxidative genes Cpt1a and Ppara. On the other hand, the STO group presented the opposite results. Finally, the obese animals presented higher levels of lipogenic proteins (ACC and FAS) and proinflammatory cytokines (TNF-α and IL-1β), but the short-term strength training was efficient in reducing this condition, regardless of body weight loss. In conclusion, there was a reduction of obesity-related hepatic lipogenesis and inflammation after short-term strength training, independent of weight loss, leading to improvements in hepatic insulin sensitivity and glycemic homeostasis in obese mice. Key points: (1) Short-term strength training (STST) reduced fat accumulation and inflammation in the liver; (2) Hepatic insulin sensitivity and HPG control were increased with STST; (3) The content and activity of ACC and content of FAS were reduced with STST; (4) STST improved hepatic fat accumulation and glycemic homeostasis; (5) STST effects were observed independently of body weight change.

scholarly journals A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults

2015 ◽  
Vol 7 (S1) ◽  
Author(s):  
Anize Delfino von Frankenberg ◽  
Anna Marina ◽  
Xiaoling Song ◽  
Holly S Callahan ◽  
Mario Kratz ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Saturated Fat ◽  
Abdominal Fat ◽  
High Fat ◽  
Obese Adults

scholarly journals Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 374-384 ◽  
Author(s):  
Lingling Ding ◽  
Gijs H. Goossens ◽  
Yvonne Oligschlaeger ◽  
Tom Houben ◽  
Ellen E. Blaak ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Cathepsin D ◽  
Insulin Infusion ◽  
Hepatic Insulin Sensitivity ◽  
Euglycaemic Clamp ◽  
Negatively Associated ◽  
Peripheral Insulin Sensitivity ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Tnf Α ◽  
Glucose Output

Abstract Aims/hypothesis Insulin resistance in skeletal muscle and liver plays a major role in the pathophysiology of type 2 diabetes. The hyperinsulinaemic–euglycaemic clamp is considered the gold standard for assessing peripheral and hepatic insulin sensitivity, yet it is a costly and labour-intensive procedure. Therefore, easy-to-measure, cost-effective approaches to determine insulin sensitivity are needed to enable organ-specific interventions. Recently, evidence emerged that plasma cathepsin D (CTSD) is associated with insulin sensitivity and hepatic inflammation. Here, we aimed to investigate whether plasma CTSD is associated with hepatic and/or peripheral insulin sensitivity in humans. Methods As part of two large clinical trials (one designed to investigate the effects of antibiotics, and the other to investigate polyphenol supplementation, on insulin sensitivity), 94 overweight and obese adults (BMI 25–35 kg/m2) previously underwent a two-step hyperinsulinaemic–euglycaemic clamp (using [6,6-2H2]glucose) to assess hepatic and peripheral insulin sensitivity (per cent suppression of endogenous glucose output during the low-insulin-infusion step, and the rate of glucose disappearance during high-insulin infusion [40 mU/(m2 × min)], respectively). In this secondary analysis, plasma CTSD levels, CTSD activity and plasma inflammatory cytokines were measured. Results Plasma CTSD levels were positively associated with the proinflammatory cytokines IL-8 and TNF-α (IL-8: standardised β = 0.495, p < 0.001; TNF-α: standardised β = 0.264, p = 0.012). Plasma CTSD activity was negatively associated with hepatic insulin sensitivity (standardised β = −0.206, p = 0.043), independent of age, sex, BMI and waist circumference, but it was not associated with peripheral insulin sensitivity. However, plasma IL-8 and TNF-α were not significantly correlated with hepatic insulin sensitivity. Conclusions/interpretation We demonstrate that plasma CTSD activity, but not systemic inflammation, is inversely related to hepatic insulin sensitivity, suggesting that plasma CTSD activity may be used as a non-invasive marker for hepatic insulin sensitivity in humans.

Insulin resistance caused by amylin in conscious rats is independent of induced hypocalcemia and fades during long-term exposure

1993 ◽  
Vol 129 (4) ◽  
pp. 360-365 ◽  
Author(s):  
Clemens Fürnsinn ◽  
Peter Nowotny ◽  
Michael Roden ◽  
Madeleine Rohac ◽  
Thomas Pieber ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Tolerance Test ◽  
Zucker Rats ◽  
Control Group ◽  
Short Term ◽  
Euglycemic Hyperinsulinemic Clamp

To compare the effect of short- vs long-term amylin infusion on insulin sensitivity, glucose tolerance and serum calcemia, euglycemic-hyperinsulinemic clamp (26 pmol·kg−1·min−1) and glucose tolerance tests (2.4 mmol/kg over 30 min) were performed in lean Zucker rats. Three infusion protocols were employed: control group: 24 h of iv saline; short-term amylin exposure: 22 h of iv saline followed by 2 h of iv amylin (20 μg/h); long-term amylin exposure: 24 h of iv amylin (20 μg/h). Insulin resistance was induced by short-term amylin infusion during euglycemic clamping, as shown by a 41% decrease in space-corrected glucose infusion rates (μmol·kg−1·min−1; control group, 106.0±15.0; short-term iv amylin, 62.7±15.0; p<0.00 5). After long-term amylin exposure, insulin sensitivity was identical to control values (109.9±6.7). This fading action of amylin was confirmed by data from the glucose tolerance test, demonstrating glucose intolerance after short- but not after long-term amylin exposure. Serum calcium concentration decreased during short-term (2 h) amylin infusion (from 2.52±0.15 to 2.09±0.12 mmol/l; p<0.01) and hypocalcemia of a similar extent also was present after 22 h and 24 h of amylin exposure (2.10±0.09 and 2.04±0.14 mmol/l, respectively). The data demonstrate that short-term amylin infusion induces insulin resistance and glucose intolerance, both of which vanish during long-term (>22 h) amylin exposure, being apparently independent of induced hypocalcemia.

scholarly journals Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

2013 ◽  
Vol 305 (10) ◽  
pp. E1292-E1298 ◽  
Author(s):  
Steven K. Malin ◽  
Jacob M. Haus ◽  
Thomas P. J. Solomon ◽  
Alecia Blaszczak ◽  
Sangeeta R. Kashyap ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Metabolic Flexibility ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Hepatic Insulin Sensitivity ◽  
Peripheral Insulin Sensitivity ◽  
Chronic Hyperglycemia

Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m2) adults were categorized as IFG ( n = 8), IGT ( n = 8), or IFG + IGT ( n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m2·min−1) with [6,6-2H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT ( P < 0.05). Exercise reduced glucose iAUCOGTT in IGT only ( P < 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity ( P < 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal ( P < 0.05). Adults with IFG + IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

Short-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet

2019 ◽  
Vol 128 (01) ◽  
pp. 30-37
Author(s):  
Luciele Guerra Minuzzi ◽  
Gabriel Keine Kuga ◽  
Leonardo Breda ◽  
Rafael Calais Gaspar ◽  
Vitor Rosetto Muñoz ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Resistance Training ◽  
High Fat Diet ◽  
Calorie Intake ◽  
Hepatic Tissue ◽  
Chow Diet ◽  
Adapter Protein ◽  
High Fat ◽  
Short Term

Abstract Background APPL1, an adapter protein, interact directly with adiponectin receptors mediating adiponectin signaling and acting as a critical regulator of the crosstalk between adiponectin and insulin signaling pathway. The inadequate level of physical activity, high-calorie intake, or both lead to adverse consequences on health, like insulin resistance. On the order hand, physical exercise acts positively in the insulin action. Purpose Here, we investigated the effects of short-term resistance training (RT) on APPL1 content and adiponectin pathway in the liver of mice fed a long-term high-fat diet. Methods Swiss mice were distributed into 3 groups: Mice that fed a chow diet (CTR); Mice fed a high-fat diet for 16 months (HFD); and mice fed a high-fat diet for 16 months and submitted to a climbing ladder exercise (RT) for 7 days (HFD-EXE). Results The results show that short-term RT increases the APPL1 content but wasn’t able to alter AdipoR1 and AdipoR2 content in the liver of HFD-EXE mice. However, this increase in the APPL1 content in response to RT was accompanied by improvement in the insulin sensitivity. Conclusion In summary, our data suggested that short-term RT improves glycemic homeostasis and increases APPL1 in the hepatic tissue of mice treated with long-term high-fat diet.

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