Postprandial chylomicrons and adipose tissue lipoprotein lipase are altered in type 2 diabetes independently of obesity and whole-body insulin resistance

2008 ◽  
Vol 18 (8) ◽  
pp. 531-538 ◽  
Author(s):  
Giovanni Annuzzi ◽  
Rosalba Giacco ◽  
Lidia Patti ◽  
Lucrezia Di Marino ◽  
Claudia De Natale ◽  
...  
Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1790-P ◽  
Author(s):  
GRETHA J. BOERSMA ◽  
KERSTIN HEURLING ◽  
MARIA J. PEREIRA ◽  
EMIL JOHANSSON ◽  
MARK LUBBERINK ◽  
...  

2018 ◽  
Vol 50 (08) ◽  
pp. 627-639 ◽  
Author(s):  
Gretha Boersma ◽  
Emil Johansson ◽  
Maria Pereira ◽  
Kerstin Heurling ◽  
Stanko Skrtic ◽  
...  

AbstractWe assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=–0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.


2005 ◽  
Vol 34 (2) ◽  
pp. 299-315 ◽  
Author(s):  
Young Ho Suh ◽  
Younyoung Kim ◽  
Jeong Hyun Bang ◽  
Kyoung Suk Choi ◽  
June Woo Lee ◽  
...  

Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age- and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating > 1.3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats at 12 weeks of age, expression of lipogenic genes was decreased in liver but increased in skeletal muscle of 12 week old diabetic ZDF rats. These results suggest that impairment of hepatic lipogenesis accompanied with the reduced lipogenesis of adipose tissue may contribute to development of diabetes in ZDF rats by increasing lipogenesis in skeletal muscle. Moreover, expression of antioxidant defense genes was decreased in the liver of 12-week old diabetic ZDF rats as well as in the adipose tissue of ZDF rats both at 6 and 12 weeks of age. Cytochrome P450 (CYP) genes were also significantly reduced in 12 week old diabetic liver of ZDF rats. Genes involved in glucose utilization were downregulated in skeletal muscle of diabetic ZDF rats, and the hepatic gluconeogenic gene was upregulated in diabetic ZDF rats. Genes commonly expressed in all three tissue types were also observed. These profilings might provide better fundamental understanding of insulin resistance and development of type 2 diabetes.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chuanyan Wu ◽  
Yan Borné ◽  
Rui Gao ◽  
Maykel López Rodriguez ◽  
William C. Roell ◽  
...  

AbstractThe hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2979 ◽  
Author(s):  
Wilrike J. Pasman ◽  
Robert G. Memelink ◽  
Johan de Vogel-Van den Bosch ◽  
Mark P. V. Begieneman ◽  
Willem J. van den Brink ◽  
...  

(1) Background: Recent research showed that subtypes of patients with type 2 diabetes may differ in response to lifestyle interventions based on their organ-specific insulin resistance (IR). (2) Methods: 123 Subjects with type 2 diabetes were randomized into 13-week lifestyle intervention, receiving either an enriched protein drink (protein+) or an isocaloric control drink (control). Before and after the intervention, anthropometrical and physiological data was collected. An oral glucose tolerance test was used to calculate indices representing organ insulin resistance (muscle, liver, and adipose tissue) and β-cell functioning. In 82 study-compliant subjects (per-protocol), we retrospectively examined the intervention effect in patients with muscle IR (MIR, n = 42) and without MIR (no-MIR, n = 40). (3) Results: Only in patients from the MIR subgroup that received protein+ drink, fasting plasma glucose and insulin, whole body, liver and adipose IR, and appendicular skeletal muscle mass improved versus control. Lifestyle intervention improved body weight and fat mass in both subgroups. Furthermore, for the MIR subgroup decreased systolic blood pressure and increased VO2peak and for the no-MIR subgroup, a decreased 2-h glucose concentration was found. (4) Conclusions: Enriched protein drink during combined lifestyle intervention seems to be especially effective on increasing muscle mass and improving insulin resistance in obese older, type 2 diabetes patients with muscle IR.


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