Effect of adipocyte β3-adrenergic receptor activation on the type 2 diabetic MKR mice

2006 ◽  
Vol 290 (6) ◽  
pp. E1227-E1236 ◽  
Author(s):  
Hyunsook Kim ◽  
Patricia A. Pennisi ◽  
Oksana Gavrilova ◽  
Stephanie Pack ◽  
William Jou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Receptor Activation ◽  
Whole Body ◽  
Acid Oxidation ◽  
Adrenergic Agonists ◽  
Nonobese Diabetic ◽  
Type 2 Diabetic

The antiobesity and antidiabetic effects of the β3-adrenergic agonists were investigated on nonobese type 2 diabetic MKR mice after injection with a β3-adrenergic agonist, CL-316243. An intact response to acute CL-316243 treatment was observed in MKR mice. Chronic intraperitoneal CL-316243 treatment of MKR mice reduced blood glucose and serum insulin levels. Hyperinsulinemic euglycemic clamps exhibited improvement of the whole body insulin sensitivity and glucose homeostasis concurrently with enhanced insulin action in liver and adipose tissue. Treating MKR mice with CL-316243 significantly lowered serum and hepatic lipid levels, in part due to increased whole body triglyceride clearance and fatty acid oxidation in adipocytes. A significant reduction in total body fat content and epididymal fat weight was observed along with enhanced metabolic rate in both wild-type and MKR mice after treatment. These data demonstrate that β3-adrenergic activation improves the diabetic state of nonobese diabetic MKR mice by potentiation of free fatty acid oxidation by adipose tissue, suggesting a potential therapeutic role for β3-adrenergic agonists in nonobese diabetic subjects.

scholarly journals Weight Reduction and the Impaired Plasma-Derived Free Fatty Acid Oxidation in Type 2 Diabetic Subjects1

2001 ◽  
Vol 86 (4) ◽  
pp. 1638-1644
Author(s):  
E. E. Blaak ◽  
B. H. R. Wolffenbuttel ◽  
W. H. M. Saris ◽  
M. M. A. L. Pelsers ◽  
A. J. M. Wagenmakers
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Weight Reduction ◽  
Acid Oxidation ◽  
Free Fatty Acid Oxidation ◽  
Type 2 Diabetic

scholarly journals Muscle-Specific Overexpression of CD36 Reverses the Insulin Resistance and Diabetes of MKR Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4667-4676 ◽  
Author(s):  
Lisa Héron-Milhavet ◽  
Martin Haluzik ◽  
Shoshana Yakar ◽  
Oksana Gavrilova ◽  
Stephanie Pack ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Cell Function ◽  
Dominant Negative ◽  
Whole Body ◽  
Acid Oxidation

Abstract Insulin resistance is one of the primary characteristics of type 2 diabetes. Mice overexpressing a dominant-negative IGF-I receptor specifically in muscle (MKR mice) demonstrate severe insulin resistance with high levels of serum and tissue lipids and eventually develop type 2 diabetes at 5–6 wk of age. To determine whether lipotoxicity plays a role in the progression of the disease, we crossed MKR mice with mice overexpressing a fatty acid translocase, CD36, in skeletal muscle. The double-transgenic MKR/CD36 mice showed normalization of the hyperglycemia and the hyperinsulinemia as well as a marked improvement in liver insulin sensitivity. The MKR/CD36 mice also exhibited normal rates of fatty acid oxidation in skeletal muscle when compared with the decreased rate of fatty acid oxidation in MKR. With the reduction in insulin resistance, β-cell function returned to normal. These and other results suggest that the insulin resistance in the MKR mice is associated with increased muscle triglycerides levels and that whole-body insulin resistance can be, at least partially, reversed in association with a reduction in muscle triglycerides levels, although the mechanisms are yet to be determined.

scholarly journals Nesfatin-1 Stimulates Fatty-Acid Oxidation by Activating AMP-Activated Protein Kinase in STZ-Induced Type 2 Diabetic Mice

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e83397 ◽  
Author(s):  
Jing Dong ◽  
Huan Xu ◽  
Huan Xu ◽  
Peng-fei Wang ◽  
Gui-ju Cai ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Diabetic Mice ◽  
Amp Activated Protein Kinase ◽  
Type 2 Diabetic

scholarly journals Prevention of Adipose Tissue Depletion during Food Deprivation in Angiotensin Type 2 Receptor-Deficient Mice

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5078-5086 ◽  
Author(s):  
Laurent Yvan-Charvet ◽  
Patrick Even ◽  
Noël Lamandé ◽  
Pascal Ferré ◽  
Annie Quignard-Boulangé
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Physiological Role ◽  
Acid Oxidation ◽  
Ang Ii ◽  
Wild Type ◽  
Angiotensin Type 2 Receptor

Angiotensin (Ang) II is produced locally in various tissues, but its role in the regulation of tissue metabolism is still unclear. Recent studies have revealed the role of type 2 Ang II receptor (AT2R) in the control of energy homeostasis and lipid metabolism. The contribution of the AT2R to adaptation to starvation was tested using AT2R-deficient (AT2Ry/−) mice. Fasted AT2Ry/− mice exhibited a lower loss of adipose tissue weight associated to a decreased free fatty acid (FFA) release from stored lipids than the controls. In vitro studies show that Ang II causes an AT1R-mediated antilipolytic effect in isolated adipocytes. AT1R expression is up-regulated by fasting in both genotypes, but the increase is more pronounced in AT2Ry/− mice. In addition, the increased muscle β-oxidation displayed in AT2Ry/− mice on a fed state, persists after fasting compared with wild-type mice. In liver from fed mice, AT2R deficiency did not modify the expression of genes involved in fatty acid oxidation. However, in response to fasting, the large increase of the expression of this subset of genes exhibited by wild-type mice, was impaired in AT2Ry/− mice. Taken together, decreased lipolytic capacity and increased muscle fatty acid oxidation participate in the decreased plasma FFA observed in fasted AT2Ry/− mice and could account for the lower FFA metabolism in the liver. These data reveal an important physiological role of AT2R in metabolic adaptations to fasting.

scholarly journals Sustained endogenous glucose production, diminished lipolysis and non-esterified fatty acid appearance and oxidation in non-obese women at high risk of type 2 diabetes

2006 ◽  
Vol 155 (3) ◽  
pp. 469-476 ◽  
Author(s):  
Shareen Forbes ◽  
Stephen Robinson ◽  
Jason Dungu ◽  
Victor Anyaoku ◽  
Peter Bannister ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
At Risk ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Glucose Production ◽  
Whole Body ◽  
Acid Oxidation ◽  
Obese Women

Objective: To evaluate early defects in glucose production, lipolysis and fatty acid oxidation in non-obese, normally glucose tolerant women, who are nevertheless at risk of type 2 diabetes. Methods: Ten women with previous gestational diabetes (pGDM) and ten controls were studied in two 4 h infusions of stable isotopes 6,6-2H2-glucose, 1-13C-palmitate, and 1,1,2,3,3-2H5-glycerol with and without infusion of adrenaline. Fatty acid oxidation was quantified using indirect calorimetry and 13CO2 measurements. Insulin sensitivity was evaluated using the short insulin tolerance test. Results: The pGDM and control women were non-obese and carefully matched for body mass index and fat mass. Whole body insulin sensitivity and basal insulin concentrations did not differ significantly but basal glucose concentrations were increased in women with pGDM. During a 0.9% saline infusion, glucose appearance was not significantly different at the first (90–120 min) and second (210–240 min) steady states. However, glucose appearance decreased in controls but was maintained in the pGDM women (−0.33 ± 0.02 vs −0.03 ± 0.08 mg/kg per min; P = 0.004). Basal glycerol appearance (0.27 ± 0.02 vs 0.38 ± 0.03 mg/kg per min; P = 0.02), palmitate appearance (0.74 ± 0.09 vs 1.05 ± 0.09 mg/kg per min; P = 0.03) and palmitate oxidation (0.07 ± 0.01 vs 0.10 ± 0.01 mg/kg per min; P = 0.03) were lower in the pGDM women. During the adrenaline infusion, changes in glucose, glycerol and palmitate concentrations and kinetics were similar in both groups. Conclusions: Sustained glucose production during fasting is an early abnormality in non-obese subjects at risk of type 2 diabetes. Lipolysis and non-esterified fatty acid appearance and oxidation are diminished, suggesting an increased tendency to store fat. The observations are not readily attributable to differences in insulin or catecholamine sensitivity.

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