Epinephrine responsiveness is reduced in livers from trained mice

Abstract

The liver is the primary metabolic organ involved in the endogenous production of glucose through glycogenolysis and gluconeogenesis. Hepatic glucose production (HGP) is increased via neural‐hormonal mechanisms such as increases in catecholamines. To date, the effects of prior exercise training on the hepatic response to epinephrine have not been fully elucidated. To examine the role of epinephrine signaling on indices of HGP in trained mice, male C57BL/6 mice were either subjected to 12 days of voluntary wheel running or remained sedentary. Epinephrine, or vehicle control, was injected intraperitoneally on day 12 prior to sacrifice with blood glucose being measured 15 min postinjection. Epinephrine caused a larger glucose response in sedentary mice and this was paralleled by a greater reduction in liver glycogen in sedentary compared to trained mice. There was a main effect of epinephrine to increase the phosphorylation of protein kinase‐A (p‐PKA) substrates in the liver, which was driven by increases in the sedentary, but not trained, mice. Similarly, epinephrine‐induced increases in the mRNA expression of hepatic adrenergic receptors (Adra1/2a, Adrb1), and glucose‐6‐phosphatase (G6pc) were greater in sedentary compared to trained mice. The mRNA expression of cAMP‐degrading enzymes phosphodiesterase 3B and 4B (Pde3b, Pde4b) was greater in trained compared to sedentary mice. Taken together, our data suggest that prior exercise training reduces the liver's response to epinephrine. This could be beneficial in the context of training‐induced glycogen sparing during exercise.

Tang-Ping-San Decoction Remodel Intestinal Flora and Barrier to Ameliorate Type 2 Diabetes Mellitus in Rodent Model

“…Approximately 90% of endogenous glucose is produced by the liver system, which can maintain blood glucose balance by regulating gluconeogenesis, glycogenolysis, and other pathways. 61 , 62 Previous studies have shown that the inhibition of hepatic gluconeogenesis can improve blood glucose levels in patients with T2DM. 63 The liver is not only an important organ that is involved not only in the synthesis, decomposition, and metabolism of carbohydrates in the body to maintain blood glucose stability but also in the degradation, clearance, and glucose metabolism of INS.…”

High-intensity interval resistance training (HIIRT) improves liver gluconeogenesis from lactate in Swiss mice

“…Therefore, the increased glucose output during perfusion with adrenaline, especially in group T8, is probably explained by substrate increase (glycogen). The sensitivity of the catecholaminergic pathway does not seem to be altered by HIIRT, because the content of PKA, the intracellular agent of the glycogenolytic action of catecholamines (Dibe et al, 2020;Petersen et al, 2017), was unchanged.…”

“…Liver glucose release comes from glycogenolysis (glycogen degradation) and gluconeogenesis -glucose synthesis from non-carbohydrate substrates, such as glycerol, several amino acids, pyruvate and lactate (Dibe et al, 2020;Hawley et al, 2014;Jensen & Richter, 2012;Mul et al, 2015;Rui, 2014;Spriet, 2014;Stark & Kibbey, 2014;Thyfault & Bergouignan, 2020;Trefts et al, 2015). Quantitatively, lactate is the major gluconeogenic precursor in any physiological circumstance (Stark & Kibbey, 2014).…”

Exercise as an Aging Mimetic: A New Perspective on the Mechanisms Behind Exercise as Preventive Medicine Against Age-Related Chronic Disease

“…Acute exercise stimulates adipose tissue lipolysis, with low/moderate exercise eliciting a 2 to 5-fold increase in circulating free fatty acids for use in substrate metabolism ( Havel et al, 1963 ; Ahlborg et al, 1974 ; Wolfe et al, 1990 ; Romijn et al, 1993 ; Ranallo and Rhodes, 1998 ; Burguera et al, 2000 ). Moreover, acute exercise also increases liver gluconeogenesis and hepatic glucose output via catecholamine release and sympathetic activity ( Dibe et al, 2020 ) which aligns with changes in glucose production with aging.…”