Glucagonoma

Author(s):  
G.M.K. Nijher ◽  
S.R. Bloom

Glucagonomas are neuroendocrine tumours arising from the α‎ cells of the islets of Langerhans, which result in excessive secretion of glucagon and peptides derived from preproglucagon. Post-translational modification of proglucagon is tissue specific and results in various glucagon peptides (1). It is the ratio of insulin to glucagon that controls the balance of gluconeogenesis and glycogenolysis in the liver. Glucagon stimulates hepatic gluconeogenesis and inhibits both glycolysis and glycogen synthesis. It increases production of free fatty acids from triglyceride breakdown by activating hormone-sensitive lipase; these undergo fatty oxidation in the liver via acetyl CoA, forming ketone bodies. The increase in free fatty acids from lipolysis inhibits hepatic lipogenesis. Glucagon also increases muscle proteolysis, resulting in an increase in amino acid supply to the liver.

1976 ◽  
Vol 230 (2) ◽  
pp. 385-388 ◽  
Author(s):  
JA McGarr ◽  
LB Oscai ◽  
J Borensztajn

Hormone-sensitive lipase activity was measured in adipocytes of rats subjected to a 12-wk program of treadmill running. Enzyme activity in the runners sacrificed immediately after exercise increased 2.5-fold (P less than 0.001) in tissue exposed to epinephrine and threefold (P less than 0.001) in tissue not exposed to epinephrine, when the results were expressed per gram of adipose tissue. Increases of almost the same magnitude were observed in runners sacrificed 24 h after their last bout of work. These significant increases in enzyme activity, however, were the result of a significant reduction in the size of cells in the epididymal fat pads of the exercisers compared with those of the freely eating sedentary animals (68.7 +/- 2.7 mum vs. 82.0 +/- 2.7 mum; P less than 0.01). When the results were expressed on a per-cell basis, therefore, hormone-sensitive lipase activity, assayed in the presence or absence of epinephrine, was unaffected by the exercise program. These results provide evidence that the lipolytic capacity of adipocytes of normal, untrained rats is sufficiently large to meet the increased demand for free fatty acids imposed by the exercise program without the need for an adaptive increase in enzyme activity.


2018 ◽  
Vol 108 (4) ◽  
pp. 857-867 ◽  
Author(s):  
Henrik H Thomsen ◽  
Nikolaj Rittig ◽  
Mogens Johannsen ◽  
Andreas B Møller ◽  
Jens Otto Jørgensen ◽  
...  

Abstract Background Acute inflammation, and subsequent release of bacterial products (e.g. LPS), inflammatory cytokines, and stress hormones, is catabolic, and the loss of lean body mass predicts morbidity and mortality. Lipid intermediates may reduce protein loss, but the roles of free fatty acids (FFAs) and ketone bodies during acute inflammation are unclear. Objective We aimed to test whether infusions of 3-hydroxybutyrate (3OHB), FFAs, and saline reduce protein catabolism during exposure to LPS and Acipimox (to restrict and control endogenous lipolysis). Design A total of 10 healthy male subjects were randomly tested 3 times, with: 1) LPS, Acipimox (Olbetam) and saline, 2) LPS, Acipimox, and nonesterified fatty acids (Intralipid), and 3) LPS, Acipimox, and 3OHB, during a 5-h basal period and a 2-h hyperinsulinemic, euglycemic clamp. Labeled phenylalanine, tyrosine, and urea tracers were used to estimate protein kinetics, and muscle biopsies were taken for Western blot analysis of protein metabolic signaling. Results 3OHB infusion increased 3OHB concentrations (P < 0.0005) to 3.5 mM and decreased whole-body phenylalanine-to-tyrosine degradation. Basal and insulin-stimulated net forearm phenylalanine release decreased by >70% (P < 0.005), with both appearance and phenylalanine disappearance being profoundly decreased. Phosphorylation of eukaryotic initiation factor 2α at Ser51 was increased in skeletal muscle, and S6 kinase phosphorylation at Ser235/236 tended (P = 0.074) to be decreased with 3OHB infusion (suggesting inhibition of protein synthesis), whereas no detectable effects were seen on markers of protein breakdown. Lipid infusion did not affect phenylalanine kinetics, and insulin sensitivity was unaffected by interventions. Conclusion During acute inflammation, 3OHB has potent anticatabolic actions in muscle and at the whole-body level; in muscle, reduction of protein breakdown overrides inhibition of synthesis. This trial was registered at clinicaltrials.gov as NCT01752348.


1982 ◽  
Vol 38 (5) ◽  
pp. 1255-1260 ◽  
Author(s):  
D. E. Rhoads ◽  
M. A. Kaplan ◽  
N. A. Peterson ◽  
E. Raghupathy

1993 ◽  
Vol 74 (6) ◽  
pp. 2711-2717 ◽  
Author(s):  
D. A. MacLean ◽  
T. E. Graham

This study examined the effects of branched-chain amino acid (BCAA) supplementation on amino acid and ammonia (NH3) responses during prolonged exercise in humans. Seven men cycled for 60 min at 75% of maximal O2 uptake after 45 min of either placebo (dextrose, 77 mg/kg) or BCAA (leucine + isoleucine + valine, 77 mg/kg) supplementation. Plasma samples (antecubital vein) were collected at rest and during exercise and analyzed for plasma NH3 and amino acids, whole blood glucose and lactate, and serum free fatty acids and glycerol. After BCAA administration, plasma BCAA levels increased from 375 +/- 22 to 760 +/- 80 microM (P < 0.05) by the onset of exercise and remained elevated throughout the experiment. Plasma NH3 concentrations increased continually during exercise for both trials and were higher (P < 0.05) after BCAA supplementation than after placebo administration. The mean plasma NH3 increase from rest to 60 min was 79 +/- 10 and 53 +/- 4 microM for BCAA and placebo trials, respectively. Plasma alanine and glutamine concentrations were elevated (P < 0.05) during exercise for both treatments. However, only glutamine concentrations were greater (P < 0.05) for BCAA trial than for placebo trial during exercise. There were no significant differences between treatments for glucose, lactate, free fatty acids, and glycerol or any other plasma amino acid. These data suggest that increased BCAA availability before exercise, when initial muscle glycogen is normal, results in significantly greater plasma NH3 responses during exercise than does placebo administration.


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