Premium
Enhanced Hepatic Insulin Sensitivity With Inhibited Gluconegenesis In Native High Altitude Rats
Author(s) -
ALHashem Fahaid Hassan,
AlMusa Hassan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb701
Subject(s) - medicine , endocrinology , gluconeogenesis , phosphoenolpyruvate carboxykinase , insulin , glucose transporter , glucokinase , insulin resistance , ampk , basal (medicine) , glucose uptake , biology , carbohydrate metabolism , chemistry , protein kinase a , metabolism , kinase , biochemistry , enzyme
Background high‐altitude (HA) populations had lower basal glucose levels as compared to low altitude (LA) natives and the mechanism(s) behind this is lacking. Interestingly, insulin, 5′ adenosine monophosphate‐activated protein kinase (AMPK) are able to restrain hepatic gluconeogenesis by inhibiting expression of Glucose 6‐phosphatase (G6Pase) and Phosphoenolpyruvate carboxykinase (PEPCK). Aim To test the hypothesis that HA have lower rate of hepatic gluconeogenesis due to enhanced insulin signaling and/or activation of hepatic AMPK under both basal and glucose stimulation. Methods Male rats of match aged, diet, genetic background and native to LA and HA areas were used. Fating plasma glucose and insulin levels were determined after which i.p glucose, pyruvate and insulin tolerance tests (IPGTT, IPPTT and IPITT, respectively) were carried out. Under basal or after insulin stimulation, liver samples were collected and real‐time reverse transcription‐PCR (qRT‐PCR) and western blotting were carried out. Results HA rats had stable basal insulin levels with significant lower basal glucose levels and Insulin resistance index (HOMA‐IR) with enhanced glucose clearance and insulin tolerance. Gluconeogenesis was significantly inhibited in HA rat as evident by decreased glucose production after IPPTT. HA rats had inhibited lower protein levels of Glucose transporter 2 (GLUT‐2) and G6Pase and PEPCK under basal and insulin stimulation. Concomitantly, HA rats had had higher levels of the following antibodies p‐IRS(tyr 612), p‐Akt and p‐FOX01 and lower levels of p‐mTOR/p‐70S6K/P‐IRS(ser307) suggesting enhanced hepatic insulin signaling. however, levels of AMPK, p‐AMPK and AS160 were not significantly different between LA and HA rats. In conclusion, our novel data is the first to show that HA native rats exhibit lower glucose levels and HOMA‐IR, at least, due to inhibited gluconeogenesis which is mediated through enhanced hepatic insulin but not AMPK signaling.