scholarly journals Improved Lipid and Lipoprotein Profile, Hepatic Insulin Sensitivity, and Glucose Tolerance in 11β-Hydroxysteroid Dehydrogenase Type 1 Null Mice

2001 ◽  
Vol 276 (44) ◽  
pp. 41293-41300 ◽  
Author(s):  
Nicholas M. Morton ◽  
Megan C. Holmes ◽  
Catherine Fiévet ◽  
Bart Staels ◽  
Anne Tailleux ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Hydroxysteroid Dehydrogenase ◽  
Lipoprotein Profile ◽  
Hepatic Insulin Sensitivity

scholarly journals Selective Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Improves Hepatic Insulin Sensitivity in Hyperglycemic Mice Strains

Endocrinology ◽  
2003 ◽  
Vol 144 (11) ◽  
pp. 4755-4762 ◽  
Author(s):  
Pēteris Alberts ◽  
Cecilia Nilsson ◽  
Göran Selén ◽  
Lars O. M. Engblom ◽  
Naimie H. M. Edling ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Selective Inhibition ◽  
Hydroxysteroid Dehydrogenase ◽  
Hepatic Insulin Sensitivity

scholarly journals Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xing Xiao ◽  
Gagik Yeghiazaryan ◽  
Simon Hess ◽  
Paul Klemm ◽  
Anna Sieben ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Raphe Nucleus ◽  
Receptor Type ◽  
Serotonergic Neurons ◽  
Dynamic Regulation ◽  
Brown Adipose ◽  
Raphe Pallidus

AbstractThe wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inactivation of orexin receptor type 1 in serotonin transporter-expressing cells of mice reduced insulin sensitivity in diet-induced obesity, mainly by decreasing glucose utilization in brown adipose tissue and skeletal muscle. Selective inactivation of orexin receptor type 2 improved glucose tolerance and insulin sensitivity in obese mice, mainly through a decrease in hepatic gluconeogenesis. Optogenetic activation of orexin neurons in lateral hypothalamus or orexinergic fibers innervating raphe pallidus impaired or improved glucose tolerance, respectively. Collectively, the present study assigns orexin signaling in serotonergic neurons critical, yet differential orexin receptor type 1- and 2-dependent functions in the regulation of systemic glucose homeostasis.

scholarly journals Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance

Diabetologia ◽  
1995 ◽  
Vol 38 (6) ◽  
pp. 699-704 ◽  
Author(s):  
T. S. Berrish ◽  
C. S. Hetherington ◽  
K. G. M. M. Alberti ◽  
M. Walker
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Hepatic Insulin Sensitivity

DPP4 deletion in adipose tissue improves hepatic insulin sensitivity in diet-induced obesity

2020 ◽  
Vol 318 (5) ◽  
pp. E590-E599 ◽  
Author(s):  
Tania Romacho ◽  
Henrike Sell ◽  
Ira Indrakusuma ◽  
Diana Roehrborn ◽  
Tamara R. Castañeda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Hepatic Insulin Sensitivity ◽  
Dipeptidyl Peptidase 4 ◽  
Diet Induced Obesity ◽  
Hepatic Fat ◽  
Igf Binding ◽  
Igf Binding Protein

Besides a therapeutic target for type 2 diabetes, dipeptidyl peptidase 4 (DPP4) is an adipokine potentially upregulated in human obesity. We aimed to explore the role of adipocyte-derived DPP4 in diet-induced obesity and insulin resistance with an adipose tissue-specific knockout (AT-DPP4-KO) mouse. Wild-type and AT-DPP4-KO mice were fed for 24 wk with a high fat diet (HFD) and characterized for body weight, glucose tolerance, insulin sensitivity by hyperinsulinemic-euglycemic clamp, and body composition and hepatic fat content. Image and molecular biology analysis of inflammation, as well as adipokine secretion, was performed in AT by immunohistochemistry, Western blot, real-time-PCR, and ELISA. Incretin levels were determined by Luminex kits. Under HFD, AT-DPP4-KO displayed markedly reduced circulating DPP4 concentrations, proving AT as a relevant source. Independently of glucose-stimulated incretin hormones, AT-DPP4-KO had improved glucose tolerance and hepatic insulin sensitivity. AT-DPP4-KO displayed smaller adipocytes and increased anti-inflammatory markers. IGF binding protein 3 (IGFBP3) levels were lower in AT and serum, whereas free IGF1 was increased. The absence of adipose DPP4 triggers beneficial AT remodeling with decreased production of IGFBP3 during HFD, likely contributing to the observed, improved hepatic insulin sensitivity.

scholarly journals Retinoic Acid Reduces Glucocorticoid Sensitivity in C2C12 Myotubes by Decreasing 11β-Hydroxysteroid Dehydrogenase Type 1 and Glucocorticoid Receptor Activities

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2700-2708 ◽  
Author(s):  
Evelyne M. Aubry ◽  
Alex Odermatt
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Glucose Tolerance ◽  
Glucocorticoid Receptor ◽  
Hormonal Regulation ◽  
Skeletal Muscles ◽  
Metabolic Diseases ◽  
Hydroxysteroid Dehydrogenase ◽  
C2c12 Myotubes

Vitamin A is a nutrient with remarkable effects on adipose tissue and skeletal muscles, and plays a role in controlling energy balance. Retinoic acid (RA), the carboxylic form of vitamin A, has been associated with improved glucose tolerance and insulin sensitivity. In contrast, elevated glucocorticoids have been implicated in the development of insulin resistance and impaired glucose tolerance. Here, we investigated whether RA might counteract glucocorticoid effects in skeletal muscle cells by lowering 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-dependent local glucocorticoid activation and/or activation of glucocorticoid receptor (GR). We found a dose-dependent down-regulation of 11β-HSD1 mRNA expression and activity upon incubation of fully differentiated mouse C2C12 myotubes with RA. In addition, RA inhibited GR transactivation by an 11β-HSD1-independent mechanism. The presence of RA during myogenesis did not prevent myotube formation but resulted in relatively glucocorticoid-resistant myotubes, exhibiting very low 11β-HSD1 expression and GR activity. The use of selective retinoic acid receptor (RAR) and retinoid X receptor ligands provided evidence that these effects were mediated through RARγ. Importantly, short hairpin RNA against RARγ abolished the effect of RA on 11β-HSD1 and GR. In conclusion, we provide evidence for an important role of RA in the control of glucocorticoid activity during myogenesis and in myotubes. Disturbances of the nutrient and hormonal regulation of glucocorticoid action in skeletal muscles might be relevant for metabolic diseases.

Improvement of Glucose Tolerance and Hepatic Insulin Sensitivity by Oligofructose Requires a Functional Glucagon-Like Peptide 1 Receptor

Diabetes ◽  
2006 ◽  
Vol 55 (5) ◽  
pp. 1484-1490 ◽  
Author(s):  
P. D. Cani ◽  
C. Knauf ◽  
M. A. Iglesias ◽  
D. J. Drucker ◽  
N. M. Delzenne ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Hepatic Insulin Sensitivity ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

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.

scholarly journals Liver Fat Content and Hepatic Insulin Sensitivity in Overweight Patients With Type 1 Diabetes

2015 ◽  
Vol 100 (2) ◽  
pp. 607-616 ◽  
Author(s):  
Gemma Llauradó ◽  
Ksenia Sevastianova ◽  
Sanja Sädevirta ◽  
Antti Hakkarainen ◽  
Nina Lundbom ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Hepatic Insulin Sensitivity

Coenzyme Q10 does not improve peripheral insulin sensitivity in statin-treated men and women: the LIFESTAT study

2019 ◽  
Vol 44 (5) ◽  
pp. 485-492 ◽  
Author(s):  
Anja Birk Kuhlman ◽  
Thomas Morville ◽  
Tine Lovsø Dohlmann ◽  
Maria Hansen ◽  
Bo Kelly ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Coenzyme Q10 ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Men And Women ◽  
Hepatic Insulin Sensitivity ◽  
Coq10 Supplementation ◽  
Secretory Capacity

Simvastatin is a cholesterol-lowering drug that is prescribed to lower the risk of cardiovascular disease following high levels of blood cholesterol. There is a possible risk of new-onset diabetes mellitus with statin treatment but the mechanisms behind are unknown. Coenzyme Q10 (CoQ10) supplementation has been found to improve glucose homeostasis in various patient populations and may increase muscle glucose transporter type 4 content. Our aim was to investigate if 8 weeks of CoQ10 supplementation can improve glucose homeostasis in simvastatin-treated subjects. Thirty-five men and women in treatment with a minimum of 40 mg of simvastatin daily were randomized to receive either 2 × 200 mg/day of CoQ10 supplementation or placebo for 8 weeks. Glucose homeostasis was investigated with fasting blood samples, oral glucose tolerance test (OGTT) and intravenous glucose tolerance test. Insulin sensitivity was assessed with the hyperinsulinemic–euglycemic clamp. Different indices were calculated from fasting samples and OGTT as secondary measures of insulin sensitivity. A muscle biopsy was obtained from the vastus lateralis muscle for muscle protein analyzes. There were no changes in body composition, fasting plasma insulin, fasting plasma glucose, or 3-h glucose with intervention, but glycated hemoglobin decreased with time. Glucose homeostasis measured as the area under the curve for glucose, insulin, and C-peptide during OGTT was unchanged after intervention. Insulin secretory capacity was also unaltered after CoQ10 supplementation. Insulin sensitivity was unchanged but hepatic insulin sensitivity increased. No changes in muscle GLUT4 content was observed after intervention. CoQ10 supplementation does not change muscle GLUT4 content, insulin sensitivity, or secretory capacity, but hepatic insulin sensitivity may improve.

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