scholarly journals High circulating levels of RBP4 and mRNA levels of aP2, PGC-1α and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naïve type 2 diabetic subjects

2008 ◽  
Vol 263 (4) ◽  
pp. 440-449 ◽  
Author(s):  
A. Hammarstedt ◽  
J. Pihlajamäki ◽  
T. E. Graham ◽  
S. Kainulainen ◽  
B. B. Kahn ◽  
...  
2003 ◽  
Vol 284 (2) ◽  
pp. E443-E448 ◽  
Author(s):  
A. S. Lihn ◽  
T. Østergård ◽  
B. Nyholm ◽  
S. B. Pedersen ◽  
B. Richelsen ◽  
...  

Adiponectin is suggested to be an important mediator of insulin resistance. Therefore, we investigated the association between adiponectin and insulin sensitivity in 22 healthy first-degree relatives (FDR) to type 2 diabetic patients and 13 matched control subjects. Subcutaneous adipose tissue biopsies were taken before and after a hyperinsulinemic euglycemic clamp. FDR subjects were insulin resistant, as indicated by a reduced Mvalue (4.44 vs. 6.09 mg · kg−1· min−1, P < 0.05). Adiponectin mRNA expression was 45% lower in adipose tissue from FDR compared with controls ( P < 0.01), whereas serum adiponectin was similar in the two groups (6.4 vs. 6.6 μg/ml, not significant). Insulin infusion reduced circulating levels of adiponectin moderately (11–13%) but significantly in both groups ( P < 0.05). In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin ( P < 0.05) and positively correlated with insulin sensitivity ( P < 0.05). In contrast, these associations were not found in the FDR group. In conclusion, FDR have reduced adiponectin mRNA in subcutaneous adipose tissue but normal levels of circulating adiponectin. Adiponectin mRNA levels are positively correlated with insulin sensitivity in control subjects but not in FDR. These findings indicate dysregulation of adiponectin gene expression in FDR.


2012 ◽  
Vol 40 (04) ◽  
pp. 721-733 ◽  
Author(s):  
Wenfan Huang ◽  
Jie Yu ◽  
Xuming Jia ◽  
Liang Xiong ◽  
Ningxu Li ◽  
...  

Forkhead box O1 (FOXO1) plays an important role in glucose metabolism at the gene transcription level. Increased FOXO1 activity results in hyperglycemia by promoting the expression of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and inhibiting glucokinase (GK). This study evaluates the effect of Zhenqing Recipe (ZQR), a Chinese herbal medicine, on hyperglycemia and its molecular mechanisms. Type 2 diabetic rats, developed by high-fat diet combined with low-dose STZ injections, were randomly divided into untreated diabetic, ZQR and metformin group. Normal rats served as control. After an eight-week treatment, fasting blood glucose was significantly decreased and insulin sensitivity index was obviously increased in the ZQR group. ZQR also improved the oral glucose tolerance. Compared with the control group, the mRNA levels of PEPCK and G6Pase were significantly elevated, while GK mRNA expression was decreased in the liver of untreated diabetic rats. ZQR significantly reduced the mRNA levels of PEPCK and G6Pase, and increased GK mRNA expression. The hepatic mRNA and protein expression of FOXO1 in the untreated diabetic group was markedly increased compared to controls. The administration of ZQR significantly decreased the mRNA and protein levels of hepatic FOXO1. The data suggest that ZQR improves glucose metabolism and insulin sensitivity, which is accompanied with regulating mRNA expression of GK and gluconeogenic genes. This anti-diabetic effect of ZQR is due to its ability to repress hepatic FOXO1 at the mRNA and protein level.


2014 ◽  
Vol 223 (3) ◽  
pp. 217-225 ◽  
Author(s):  
Lili Guo ◽  
Penghua Fang ◽  
Mei Yu ◽  
Mingyi Shi ◽  
Ping Bo ◽  
...  

Alarin, a regulatory peptide, belongs to the galanin family and plays the same regulatory roles as galanin in orexigenic activity and energy metabolism. Our previous studies had found that galanin might facilitate insulin sensitivity via activation of its central receptors. To date, little is known about whether central alarin may exert similar effects on insulin sensitivity. In order to investigate this, alarin and its specific antagonist, alarin 6–25Cys, were administered into the cerebral ventricles of type 2 diabetic rats (T2DR) to evaluate the changes in insulin resistance. The results indicated that central treatment with alarin significantly increased the body weight of animals, the 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake, the plasma adiponectin levels, the glucose infusion rates in hyperinsulinemic–euglycemic clamp tests, the vesicle-associated membrane protein 2 as well as glucose transporter 4 (GLUT4 (SLC2A4)) protein and mRNA levels, and the ratios of GLUT4 contents in plasma membranes to total cell membranes in adipocytes, but reduced blood glucose and plasma retinol-binding protein 4 levels. These effects of alarin may be inhibited by pretreatment with alarin 6–25Cys. The above-mentioned results suggest that the central alarin projective system may facilitate insulin sensitivity and glucose uptake via the increase in GLUT4 content and GLUT4 translocation from intracellular pools to plasma membranes in T2DR.


2014 ◽  
Author(s):  
Gonzalo Piedrola ◽  
Daniel Cepero ◽  
Concepcion Gil ◽  
Jessica Ramirez ◽  
Ricardo Roa

Diabetes Care ◽  
2001 ◽  
Vol 24 (5) ◽  
pp. 875-880 ◽  
Author(s):  
P. Piatti ◽  
L. D. Monti ◽  
G. Valsecchi ◽  
F. Magni ◽  
E. Setola ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Peiran Lu ◽  
Lei Wu ◽  
Xin Guo ◽  
Siau Yen Wong ◽  
Stephen Clarke ◽  
...  

Abstract Objectives Chicken eggs have a high nutrient density. Some country guidelines recommend that people with type 2 diabetes (T2D) limit their consumption of eggs due to its high cholesterol content. However, several clinical studies showed that egg intake is associated with a lower risk of type 2 diabetes. In the current study, we sought to explore whether egg consumption improves insulin sensitivity and subsequent blood glucose management in type 2 diabetic db/db mice. Methods Six-week-old male db/db mice were fed a low-fat diet (LFD, 10 kCal % from fat) or LFD supplemented with 1% whole eggs (Egg) for 8 weeks. At the termination of the study, mice were fasted for 3 hrs prior to euthanization. Blood and other tissues were collected for laboratory assessments. Plasma metabolic parameters and pro-inflammatory cytokines were monitored by a clinical analyzer and ELISA, respectively. Hepatic and skeletal muscle mitochondrial respiratory activity was assessed by a Seahorse XFe Analyzer. Hepatic gene expression was analyzed by transcriptomics and confirmed by real-time PCR and/or Western blot. Results Egg consumption significantly increased body weight gain, lowered fasting blood glucose, insulin, and IL-6 levels, and elevated total cholesterol, HDL, LDL, and GLP-1 levels. Only the basal mitochondrial respiratory activity was decreased, and the complex II respiratory activity was increased in gastrocnemius muscles in mice fed Egg. Hepatic mitochondrial activity was not altered by diet. Mechanistically, transcriptomics results revealed that hepatic genes involved in enhanced insulin sensitivity were highly expressed, but genes in endogenous cholesterol synthesis were significantly suppressed after egg consumption. Conclusions The results suggest that egg consumption is beneficial to blood glucose control in type 2 diabetic mice. Type 2 diabetic animal could manage the cholesterol level through suppression of de novo cholesterol synthesis when consuming a high cholesterol diet, e.g., egg diet. Funding Sources National egg nutrition center grant USDA NIFA grant


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