scholarly journals miR-467 regulates inflammation and blood insulin and glucose

2019 ◽  
Author(s):  
Jasmine Gajeton ◽  
Irene Krukovets ◽  
Revanth Yendamuri ◽  
Dmitriy Verbovetskiy ◽  
Amit Vasanji ◽  
...  

AbstractObesity is associated with inflammation and insulin resistance (IR), but the regulation of insulin sensitivity (IS) and connections between IS and inflammation remain unclear. We investigated the role of miR-467a-5p, a miRNA induced by hyperglycemia, in regulating inflammation and blood glucose handling.We previously demonstrated that miR-467a-5p is induced by hyperglycemia and inhibits the production of thrombospondin-1 (TSP-1), a protein implicated in regulating inflammation. To investigate the role of miR-467 in blood glucose handling and tissue inflammation, WT C57/BL6 mice were fed chow or Western diet from 5 to 32 weeks of age and injected weekly with miR-467a-5p antagonist. Inhibiting miR-467a-5p resulted in 47% increase in macrophage infiltration and increased Il6 levels in adipose tissue, higher plasma insulin levels (98 vs 63 ng/mL), and 17% decrease in glucose clearance without increase in weight or HDL/LDL. The antagonist effect was lost in mice on Western diet. Mice lacking TSP-1 lost some but not all of the miR-467 effects, suggesting Thbs1−/− (and other unknown transcripts) are targeted by miR-467 to regulate inflammation.miR-467a-5p provides a physiological feedback when blood glucose is elevated to avoid inflammation and increased blood glucose and insulin levels, which may prevent IR.

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Varunkumar G Pandey ◽  
Lars Bellner ◽  
Victor Garcia ◽  
Joseph Schragenheim ◽  
Andrew Cohen ◽  
...  

20-HETE (20-Hydroxyeicosatetraenoic acid) is a cytochrome P450 ω-hydroxylase metabolite of arachidonic acid that promotes endothelial dysfunction, microvascular remodeling and hypertension. Previous studies have shown that urinary 20-HETE levels correlate with BMI and plasma insulin levels. However, there is no direct evidence for the role of 20-HETE in the regulation of glucose metabolism, obesity and type 2 diabetes mellitus. In this study we examined the effect of 20-SOLA (2,5,8,11,14,17-hexaoxanonadecan-19-yl-20-hydroxyeicosa-6(Z),15(Z)-dienoate), a water-soluble 20-HETE antagonist, on blood pressure, weight gain and blood glucose in Cyp4a14 knockout (Cyp4a14-/-) mice fed high-fat diet (HFD). The Cyp4a14-/- male mice exhibit high vascular 20-HETE levels and display 20-HETE-dependent hypertension. There was no difference in weight gain and fasting blood glucose between Cyp4a14-/- and wild type (WT) on regular chow. When subjected to HFD for 15 weeks, a significant increase in weight was observed in Cyp4a14-/- as compared to WT mice (56.5±3.45 vs. 30.2±0.7g, p<0.05). Administration of 20-SOLA (10mg/kg/day in drinking water) significantly attenuated the weight gain (28.7±1.47g, p<0.05) and normalized blood pressure in Cyp4a14-/- mice on HFD (116±0.3 vs. 172.7±4.6mmHg, p<0.05). HFD fed Cyp4a14-/- mice exhibited hyperglycemia as opposed to normal glucose levels in WT on a HFD (154±1.9 vs. 96.3±3.0 mg/dL, p<0.05). 20-SOLA prevented the HFD-induced hyperglycemia in Cyp4a14-/- mice (91±8mg/dL, p<0.05). Plasma insulin levels were markedly high in Cyp4a14-/- mice vs. WT on HFD (2.66±0.7 vs. 0.58±0.18ng/mL, p<0.05); corrected by the treatment with 20-SOLA (0.69±0.09 ng/mL, p<0.05). Importantly, glucose and insulin tolerance tests showed impaired glucose homeostasis and insulin resistance in Cyp4a14-/- mice on HFD; ameliorated by treatment with 20-SOLA. This novel finding that blockade of 20-HETE actions by 20-SOLA prevents HFD-induced obesity and restores glucose homeostasis in Cyp4a14-/- mice suggests that 20-HETE contributes to obesity, hyperglycemia and insulin resistance in HFD induced metabolic disorder. The molecular mechanisms underlying 20-HETE mediated metabolic dysfunction are being currently explored.


2012 ◽  
Vol 11 (1) ◽  
pp. 80 ◽  
Author(s):  
Toshitaka Muneyuki ◽  
Kei Nakajima ◽  
Atsushi Aoki ◽  
Masashi Yoshida ◽  
Hiroshi Fuchigami ◽  
...  

1981 ◽  
Vol 61 (1) ◽  
pp. 23-28 ◽  
Author(s):  
R. H. Sterns ◽  
J. Guzzo ◽  
P. U. Feig

1. Potassium infusion causes an increase in immunoreactive insulin levels in dogs, but either a small (30%) or no increase in humans. Since insulin stimulates the uptake of K+ by cells, a regulatory role for K+-induced insulin release has been postulated. To study the role of insulin in regulating cellular K+ uptake, six fasting normal volunteer subjects underwent two K+ infusions on separate days. Both infusions delivered 0.6 mmol h−1 kg−1 for 3 h. In one subject glucose was simultaneously infused at 0.67 mmol h−1 kg−1 (a rate known to increase peripheral insulin levels by 40–100%); the other infusion contained no glucose. 2. Plasma insulin levels did not increase during the glucose-free infusions. During glucose-containing infusions, insulin levels were 40% higher than those during glucose-free infusions. Despite this, neither urinary potassium excretion nor the increment in plasma K+ concentration or the calculated cellular K+ uptake differed significantly during the 3 h of glucose-free and glucose-containing infusions respectively. 3. These data do not support the view that potassium-induced insulin secretion regulates cellular potassium uptake within the physiological range of plasma K+ concentration.


1991 ◽  
Vol 66 (3) ◽  
pp. 363-379 ◽  
Author(s):  
Peter R. Ellis ◽  
Fathy M. Dawoud ◽  
Edwin R. Morris

The effectiveness of guar gum in reducing post-prandial blood glucose and plasma insulin levels in human subjects seems to depend mainly on its ability to increase the viscosity of digesta in the small intestine. However, the precise relationship between the rheological properties of guar gum (either in vitro or in vivo) and the changes in blood metabolites and hormones is unknown. The aim of the present study, therefore, was to investigate the effects of wheat breads containing guar gum samples varying in molecular weight (Mw) and particle size (characteristics that strongly influence the rheological properties of guar gum) on post-prandial blood glucose and plasma insulin levels in healthy subjects. The sensory qualities of breads containing guar-gum flours of different Mw were also evaluated using a hedonic scoring technique. No significant differences in the post-prandial blood glucose responses were found between the control and guar breads. However, all the guar breads elicited significant (P < 0.05) decreases in the post-prandial rise in plasma insulin, an effect that did not appear to be influenced by large variations in Mw or particle size of guar gum. Moreover, the sensory qualities of guar bread were markedly improved by using low Mw grades of guar gum.


Diabetologia ◽  
1974 ◽  
Vol 10 (6) ◽  
pp. 725-730 ◽  
Author(s):  
M. Hautecouverture ◽  
G. Slama ◽  
R. Assan ◽  
G. Tchobroutsky

Sign in / Sign up

Export Citation Format

Share Document