ORCID Profile
0000-0003-1962-5302
Current Organisations
Hvidovre Hospital
,
iThemba LABS
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Publisher: American Diabetes Association
Date: 09-2020
DOI: 10.2337/DB20-0062
Abstract: Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control (CON) women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle, improving glucose uptake and metabolism in both healthy in iduals and patients with type 2 diabetes. In the current study, lean hyperandrogenic women with PCOS (n = 9) and healthy CON women (n = 9) completed 14 weeks of controlled and supervised exercise training. In CON, the training intervention increased whole-body insulin action by 26% and insulin-stimulated leg glucose uptake by 53% together with increased insulin-stimulated leg blood flow and a more oxidative muscle fiber type distribution. In PCOS, no such changes were found, despite similar training intensity and improvements in VO2max. In skeletal muscle of CON but not PCOS, training increased GLUT4 and HKII mRNA and protein expressions. These data suggest that the impaired increase in whole-body insulin action in women with PCOS with training is caused by an impaired ability to upregulate key glucose-handling proteins for insulin-stimulated glucose uptake in skeletal muscle and insulin-stimulated leg blood flow. Still, other important benefits of exercise training appeared in women with PCOS, including an improvement of the hyperandrogenic state.
Publisher: American Physical Society (APS)
Date: 05-02-2016
Publisher: American Physiological Society
Date: 04-2019
DOI: 10.1152/AJPENDO.00010.2019
Abstract: Bariatric surgery results in marked body weight loss and improves type 2 diabetes in most patients with obesity. The growth differentiation factor 15 (GDF15) has recently emerged as a novel satiety factor. To begin to understand whether GDF15 is involved in mediating the effects of bariatric surgery on body weight and glycemia in humans, we measured plasma GDF15 in patients with obesity ( n = 25) and in patients with obesity and diabetes ( n = 22) before and after Roux-en-Y gastric bypass (RYGB) surgery. GDF15 was increased 1 wk after RYGB compared with before surgery (689 ± 45 vs. 487 ± 28 pg/ml, P 0.001) and GDF15 remained elevated at 3 mo (554 ± 37 pg/ml, P 0.05), at 1 yr (566 ± 37 pg/ml, P 0.05), and at 2.5–4 yr (630 ± 50 pg/ml, P 0.001) after RYGB surgery. Both age and insulin sensitivity correlated with GDF15 before the surgery ( r = 0.46, P 0.0001 and r = 0.34, P 0.001, respectively). These correlations disappeared at 2.5–4 yr following the surgery. Conversely, weight loss magnitude correlated with GDF15, measured 2.5–4 yr postsurgery ( r = 0.21, P 0.0055). In summary, circulating GDF15 increases and correlates with body weight loss following RYGB surgery.
Publisher: American Physical Society (APS)
Date: 19-05-2000
Publisher: Elsevier BV
Date: 12-2020
Publisher: IOP Publishing
Date: 10-1997
Publisher: Wiley
Date: 11-08-2019
DOI: 10.1002/JCSM.12474
Abstract: Skeletal muscle wasting is often associated with insulin resistance. A major regulator of muscle mass is the transforming growth factor β (TGF‐β) superfamily, including activin A, which causes atrophy. TGF‐β superfamily ligands also negatively regulate insulin‐sensitive proteins, but whether this pathway contributes to insulin action remains to be determined. To elucidate if TGF‐β superfamily ligands regulate insulin action, we used an adeno‐associated virus gene editing approach to overexpress an activin A inhibitor, follistatin (Fst288), in mouse muscle of lean and diet‐induced obese mice. We determined basal and insulin‐stimulated 2‐deoxy‐glucose uptake using isotopic tracers in vivo . Furthermore, to evaluate whether circulating Fst and activin A concentrations are associated with obesity, insulin resistance, and weight loss in humans, we analysed serum from morbidly obese subjects before, 1 week, and 1 year after Roux‐en‐Y gastric bypass (RYGB). Fst288 muscle overexpression markedly increased in vivo insulin‐stimulated (but not basal) glucose uptake (+75%, P 0.05) and increased protein expression and intracellular insulin signalling of AKT, TBC1D4, PAK1, pyruvate dehydrogenase‐E1α, and p70S6K, while decreasing TBC1D1 signaling ( P 0.05). Fst288 increased both basal and insulin‐stimulated protein synthesis, but no correlation was observed between the Fst288‐driven hypertrophy and the increase in insulin‐stimulated glucose uptake. Importantly, Fst288 completely normalized muscle glucose uptake in insulin‐resistant diet‐induced obese mice. RYGB surgery doubled circulating Fst and reduced activin A (−24%, P 0.05) concentration 1 week after surgery before any significant weight loss in morbidly obese normoglycemic patients, while major weight loss after 1 year did not further change the concentrations. We here present evidence that Fst is a potent regulator of insulin action in muscle, and in addition to AKT and p70S6K, we identify TBC1D1, TBC1D4, pyruvate dehydrogenase‐E1α, and PAK1 as Fst targets. Circulating Fst more than doubled post‐RYGB surgery, a treatment that markedly improved insulin sensitivity, suggesting a role for Fst in regulating glycaemic control. These findings demonstrate the therapeutic potential of inhibiting TGF‐β superfamily ligands to improve insulin action and Fst's relevance to muscle wasting‐associated insulin‐resistant conditions in mice and humans.
Publisher: American Physical Society (APS)
Date: 19-05-2000
Publisher: American Physical Society (APS)
Date: 17-08-2020
No related grants have been discovered for Kirstine Nyvold Bojsen-Møller.