LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Actions of Apolipoprotein A-IV on Insulin-Independent Glucose Control and Activation of Akt in Mouse Liver

Photo from wikipedia

Insulin resistance is a risk factor for type 2 diabetes, fatty liver and metabolic syndrome. We reported previously that apolipoprotein A-IV (ApoA4) increased insulin secretion, insulin sensitivity and improved glucose… Click to show full abstract

Insulin resistance is a risk factor for type 2 diabetes, fatty liver and metabolic syndrome. We reported previously that apolipoprotein A-IV (ApoA4) increased insulin secretion, insulin sensitivity and improved glucose uptake in adipocytes by PI3K-Akt pathways. Whether insulin sensitivity is improved by ApoA4 in mouse liver remains unclear. Here we used mice as well as hepatocytes to investigate the action of ApoA4 on glucose control and hepatic Akt activation. Liver tissues were from lean mice 2 h after a single ip injection of recombinant mouse ApoA4 (n = 5 per group) and tissue lysates were separated by Western blotting with anti-pAkt antibody. Primary mouse hepatocytes were cultured for glucose-uptake experiment and pAkt analysis after ApoA4 stimulation. Approach to block insulin secretion transiently in insulin-resistant DIO mice (6wk-HFD) and lean mice by propranolol and epinephrine was used by co-administration with glucose after a single ip injection of ApoA4 prior to being sacrificed for the liver. Treatment of the mice with ApoA4 for 2 h increased Akt phosphorylation from liver in dose-dependent in the basal state. In time and dose-dependent manner, direct action of ApoA4 on Akt activation in primary mouse hepatocytes too indicates this effect was insulin independent. ApoA4 treatment also increased [ 3 H]-2-deoxyglucose uptake by primary mouse hepatocytes. The contributions of ApoA4 on insulin-independent glucose disposal was verified with insulin blocking. ApoA4 to an equal extent of direct insulin-independent and insulin-dependent, enhanced blood glucose clearance in both insulin-resistant DIO mice and lean mice. With the glucose challenge, ApoA4 treatment resulted in an increase in Akt phosphorylation in liver, heart and brown adipose tissue in insulin-dependent in lean mice, but which was in insulin-independent only in liver in DIO mice. Data imply ApoA4 as a novel antidiabetic drug to treatments of diabetic diseases. Disclosure J. He: None. J. Zhao: None. Z. Yang: None. J. Zhang: None. S. Wei: None. S. Li: None. X. Li: None.

Keywords: insulin; insulin independent; apoa4; liver; mice; mouse

Journal Title: Diabetes
Year Published: 2018

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.