Liver, but Not Muscle, Has an Entrainable Metabolic Memory

Abstract

Hyperglycemia in the hospitalized setting is common, especially in patients that receive nutritional support either continuously or intermittently. As the liver and muscle are the major sites of glucose disposal, we hypothesized their metabolic adaptations are sensitive to the pattern of nutrient delivery. Chronically catheterized, well-controlled depancreatized dogs were placed on one of three isocaloric diets: regular chow diet once daily (Chow) or a simple nutrient diet (ND) that was given either once daily (ND-4) or infused continuously (ND-C). Intraportal insulin was infused to maintain euglycemia. After 5 days net hepatic (NHGU) and muscle (MGU) glucose uptake and oxidation were assessed at euglycemia (120 mg/dl) and hyperglycemia (200 mg/dl) in the presence of basal insulin. While hyperglycemia increased both NHGU and MGU in Chow, NHGU was amplified in both groups receiving ND. The increase was associated with enhanced activation of glycogen synthase, glucose oxidation and suppression of pyruvate dehydrogenase kinase-4 (PDK-4). Accelerated glucose-dependent muscle glucose uptake was only evident with ND-C. This was associated with a decrease in PDK-4 expression and an increase in AMP-activated protein kinase (AMPK) phosphorylation. Interestingly, ND-C markedly increased hepatic FGF-21 expression. Thus, augmentation of carbohydrate disposal in the liver, as opposed to the muscle, is not dependent on the pattern of nutrient delivery.

Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle

“…The prevention or treatment of hyperglycemia requires strategies to promote tissue‐specific metabolic adaptations, in the liver and muscle for example, to increase the capacity of glucose storage and oxidation. After an overload of glucose after a meal, the glucose uptake by skeletal muscle is increased, thereby suggesting both increased glycogen synthesis and pyruvate oxidation [Chen et al, ]. Relative to tissue mass, the skeletal muscle is responsible for the majority of insulin‐stimulated whole‐body glucose disposal.…”

Haploinsufficiency of the Myc regulator Mtbp extends survival and delays tumor development in aging mice

“…Mice were sacrificed by cervical dislocation. Liver and gastrocnemius muscle were frozen with a Wallenburg clamp pre-cooled in liquid nitrogen as previously described [42]. Brown fat pads were collected and frozen.…”