Endoplasmic reticulum stress increases glucose production in vivo via effects on liver glycogenolysis and glucose-6-phosphatase activity
Date
2006
Authors
Gonzales, Jon C., author
Wang, Dong, author
Wei, Yuren, author
Pagliassotti, Michael J., author
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Abstract
Recent evidence suggests that endoplasmic reticulum (ER) stress can induce impairments in both insulin secretion and insulin action. The aim of the present study was to examine the effects of ER stress on glucose production in vivo. Fasted rats were anesthetized and catheters were placed in the carotid artery, jugular vein, and jejunal vein. A pancreatic clamp was performed in which somatostatin was infused to inhibit pancreatic insulin and glucagon secretion. These hormones were then replaced at basal levels. To examine the effects of ER stress on glucose production, 6,6-2H2 Glucose was infused in the absence (CON, n =4) or presence of jejunal vein tunicamycin delivery (TUN, n =6). TUN induces ER stress through inhibition of protein glycosylation. Arterial insulin, glucagon, corticosterone, and free fatty acid concentrations were constant throughout experiments and were not different between groups. Glucose concentration and production increased by 76.2+-24.2 mg/dl and 2.6+-1.2 mg/kg/min (mean+-SDEV), respectively, in TUN, but did not change in CON. Liver glucose-6-phosphatase (G6Pase) and phosphoenopyruvate carboxykinase mRNA were not different between groups. Liver, but not kidney, G6Pase activity (nmoles/mg protein/30min) was increased in TUN (7.2+-2.1) vs. CON (0.2+-0.3). Liver glycogen concentration was reduced by 62% in TUN vs. CON. These data suggest that experimental induction of ER stress can increase the production of glucose in vivo, in part, via activation of hepatic glycogenolysis and G6Pase.
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Subject
Endoplasmic reticulum
Glucose -- Synthesis
Glucose-6-phosphatase