Beta-aminoisobutyric acid is released by contracting human skeletal muscle and lowers insulin release from INS-1 832/3 cells by mediating mitochondrial energy metabolism
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Beta-aminoisobutyric acid is released by contracting human skeletal muscle and lowers insulin release from INS-1 832/3 cells by mediating mitochondrial energy metabolism. / Barlow, Jonathan P; Karstoft, Kristian; Vigelsø, Andreas; Gram, Martin; Helge, Jørn W; Dela, Flemming; Pappan, Kirk; O'Neil, Donna; Dunn, Warwick; Solomon, Thomas P J.
In: Metabolism open, Vol. 7, 2020, p. 100053.Research output: Contribution to journal › Journal article › peer-review
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T1 - Beta-aminoisobutyric acid is released by contracting human skeletal muscle and lowers insulin release from INS-1 832/3 cells by mediating mitochondrial energy metabolism
AU - Barlow, Jonathan P
AU - Karstoft, Kristian
AU - Vigelsø, Andreas
AU - Gram, Martin
AU - Helge, Jørn W
AU - Dela, Flemming
AU - Pappan, Kirk
AU - O'Neil, Donna
AU - Dunn, Warwick
AU - Solomon, Thomas P J
N1 - © 2020 The Author(s).
PY - 2020
Y1 - 2020
N2 - Aims/hypothesis: This study aimed to examine if beta-aminoisobutyric acid (BAIBA) is (i) secreted by skeletal muscle in humans during exercise, (ii) associated with insulin secretory function in vivo, and (iii) directly linked with acute glucose-mediated insulin release by pancreatic beta cells in vitro.Methods: Following 2-weeks of single-leg immobilization, plasma BAIBA concentrations were measured in the brachial artery and the femoral veins of each leg in healthy male subjects, at rest and during two-legged dynamic knee-extensor exercise. During a 2-h hyperglycamic clamp, insulin secretory function and levels of plasma BAIBA were assessed in non-diabetic individuals, non-diabetic individuals following 24-h hyperglycemia and patients with type 2 diabetes. Direct effects of BAIBA on acute glucose-mediated insulin release were probed in INS-1832/3 cells under normal and 'diabetes-like' conditions. Finally, the effect of BAIBA on mitochondrial function was assessed in INS-1832/3 cells using extracellular flux analysis.Results: (i) BAIBA is released from skeletal muscle at rest and during exercise under healthy conditions but is suppressed during exercise following leg immobilization, (ii) plasma BAIBA concentrations inversely associate with insulin secretory function in humans, (iii) BAIBA lowers mitochondrial energy metabolism in INS-1 832/3 cells in parallel with decreased insulin secretionConclusion/interpretation: BAIBA is a myokine released by skeletal muscle during exercise and indepedantly alters the triggering pathway of insulin secretion in cultured INS-1832/3 cells.
AB - Aims/hypothesis: This study aimed to examine if beta-aminoisobutyric acid (BAIBA) is (i) secreted by skeletal muscle in humans during exercise, (ii) associated with insulin secretory function in vivo, and (iii) directly linked with acute glucose-mediated insulin release by pancreatic beta cells in vitro.Methods: Following 2-weeks of single-leg immobilization, plasma BAIBA concentrations were measured in the brachial artery and the femoral veins of each leg in healthy male subjects, at rest and during two-legged dynamic knee-extensor exercise. During a 2-h hyperglycamic clamp, insulin secretory function and levels of plasma BAIBA were assessed in non-diabetic individuals, non-diabetic individuals following 24-h hyperglycemia and patients with type 2 diabetes. Direct effects of BAIBA on acute glucose-mediated insulin release were probed in INS-1832/3 cells under normal and 'diabetes-like' conditions. Finally, the effect of BAIBA on mitochondrial function was assessed in INS-1832/3 cells using extracellular flux analysis.Results: (i) BAIBA is released from skeletal muscle at rest and during exercise under healthy conditions but is suppressed during exercise following leg immobilization, (ii) plasma BAIBA concentrations inversely associate with insulin secretory function in humans, (iii) BAIBA lowers mitochondrial energy metabolism in INS-1 832/3 cells in parallel with decreased insulin secretionConclusion/interpretation: BAIBA is a myokine released by skeletal muscle during exercise and indepedantly alters the triggering pathway of insulin secretion in cultured INS-1832/3 cells.
U2 - 10.1016/j.metop.2020.100053
DO - 10.1016/j.metop.2020.100053
M3 - Journal article
C2 - 32924003
VL - 7
SP - 100053
JO - Metabolism open
JF - Metabolism open
SN - 2589-9368
ER -
ID: 260692423