Exercise restores brain insulin sensitivity in sedentary adults who are overweight and obese

Kullmann, Stephanie; Goj, Thomas; Veit, Ralf; Fritsche, Louise; Wagner, Lore; Schneeweiss, Patrick; Hoene, Miriam; Hoffmann, Christoph; Machann, Jürgen; Nieß, Andreas M.; Preißl, Hubert; Birkenfeld, Andreas L.; Häring, Hans‐Ulrich; Fritsche, Andreas; Moller, Anja; Weigert, Cora; Heni, Martin

doi:10.1172/jci.insight.161498

Cited by 32 publications

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References 71 publications

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“…A 24‐week intervention with intranasal insulin led to increased gait speed in elderly participants with and without T2D 61 . Furthermore, we were able to show improved central insulin responsiveness in the striatum after an 8‐week exercise intervention, which was linked to improved cognitive and metabolic functions in middle‐aged adults at high risk of developing T2D 33 . In elderly dieters, weight loss success was identified to be directly related to improved central insulin action in the striatum 34 .…”

Section: Discussionmentioning

confidence: 69%

“…Our current findings show that brain insulin action is region‐specific both in the responsiveness as well as in associations with peripheral insulin sensitivity or ageing. Furthermore, brain insulin sensitivity can potentially be restored through pharmacological, 32 exercise 33 and weight loss interventions 34 . These interventions may potentially be tailored to improve peripheral metabolism or age‐dependent alterations by targeting regional‐specific brain insulin action.…”

Section: Discussionmentioning

confidence: 99%

“…This regional CBF responsiveness is affected by abdominal obesity, T2D and ageing, indicating alteration in brain insulin sensitivity 6,30 . Furthermore, recent studies show that brain insulin responsiveness can potentially be normalized in persons with obesity and a high risk to develop T2D through pharmacological, 32 exercise 33 and weight loss interventions 34 …”

Section: Introductionmentioning

confidence: 99%

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Brain insulin responsiveness is linked to age and peripheral insulin sensitivity

Wagner

Veit

Kübler

et al. 2023

Diabetes Obesity Metabolism

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Aims: Insulin action in the brain influences cognitive processes, peripheral metabolism and eating behaviour. However, the influence of age and peripheral insulin sensitivity on brain insulin action remains unclear. Materials and Methods:We used intranasal administration of insulin and functional magnetic resonance imaging in a randomized, placebo-controlled within-subject design in 110 participants (54 women, body mass index 18-49 kg/m 2 , age 21-74 years). Cerebral blood flow was measured before and after nasal spray application to assess brain insulin action. Peripheral insulin sensitivity was assessed by a five-point oral glucose tolerance test. Linear regressions were used to investigate associations between age and peripheral insulin sensitivity with brain insulin action in predefined region of interests (i.e. insulin-sensitive brain regions).Results: We found significant negative associations between age and insulin action in the hippocampus (β = -0.215; p = .017) and caudate nucleus (β = -0.184; p = .047); and between peripheral insulin sensitivity and insulin action in the amygdala (β = -0.190, p = .023). Insulin action in the insular cortex showed an interaction effect between age and peripheral insulin sensitivity (β = -0.219 p = .005). Furthermore, women showed the strongest negative association between age and hippocampal insulin action, while men showed the strongest associations with peripheral insulin sensitivity and age in reward-related brain regions. Conclusion:We could show a region-specific relationship between brain insulin responsiveness, age and peripheral insulin sensitivity. Our findings underline the need to study brain insulin action in both men and women and further substantiate that brain insulin sensitivity is a possible link between systemic metabolism and neurocognitive functions.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Brain insulin responsiveness is linked to age and peripheral insulin sensitivity

Wagner

Veit

Kübler

et al. 2023

Diabetes Obesity Metabolism

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“…Ein wichtiger Bestandteil der Kur ist ein moderates aerobes Ausdauertraining zur Verbesserung der Mitochondrienfunktion und Insulinsensitivität im Hirn 15 . Es geht auch hier um die richtige Dosierung, weil hochintensive Belastungen die Verdauungsleistung, die Darmdurchblutung und Mukosabarriere negativ beeinflussen.…”

Section: Effekte Der Mayr-therapieunclassified

“…Die Interaktionen bestehen immer in beiden Richtungen, und die verlängerte Lichtexposition spielt dabei ebenso eine Rolle[11]. Insulinsensitivität im Hirn[15]. Es geht auch hier um die richtige Dosierung, weil hochintensive Belastungen die Verdauungsleistung, die Darmdurchblutung und Mukosabarriere negativ beeinflussen.…”

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„Ein voller Bauch schläft nicht gut“ – Salutogener Therapieansatz durch Integration der Mayr-Medizin bei Schlafstörungen

Fegerl¹

2023

Erfahrungsheilkunde

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ZusammenfassungDer gesunde Schlaf ist vielfältigen Störeinflüssen ausgesetzt. Der Verdauungstrakt spielt dabei eine große Rolle. Werden Patientinnen und Patienten mit dem ganzen Spektrum an Schlafstörungen nach den Diagnosekriterien nach Mayr zur Darmgesundheit untersucht, liegt in den meisten Fällen ein überforderter Darm bzw. Verdauungstrakt vor, die den ganzen Organismus belasten. Noch bevor ein medizinischer Krankheitswert erkennbar wird, kann eine Mayr-Therapie präventiv oder kurativ eingesetzt und dadurch können Stoffwechselvorgänge günstig beeinflusst werden: Gewicht, ektopes und viszerales Fett, zirkadianer Rhythmus, Darmgesundheit, Entzündungs-, Hormon- und Immunmodulation, besonders aber auch die Lebensstilfaktoren Ernährung, Bewegung und vegetative Balance.

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Imaging the brain to assess brain insulin action

Kullmann

2023

Alzheimer's & Dementia

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BackgroundEver since the brain was identified as an insulin‐sensitive organ, it was quickly appreciated that insulin action in the brain affects cognitive and metabolic processes [1]. Epidemiological evidence suggests a strong link between reduced peripheral insulin sensitivity and age‐related neurodegenerative processes, including Alzheimer’s disease (AD) [2].MethodCharacterization of brain insulin resistance in humans is challenging and relies on different neuroimaging methods in combination with insulin stimulation techniques. In my talk, I will focus on the administration of intranasal insulin, which has been established over the last decades to disentangle peripheral from brain insulin effects [1]. In combination with functional neuroimaging, I will show recent data on the quantification of brain insulin sensitivity non‐invasively in humans of different age and weight groups [3].ResultWe could show that intranasal insulin can affect region‐specific activity and functional connectivity of the human brain. These diverse central insulin responses largely depend on its action in the hypothalamus, amygdala, hippocampus, striatum and parts of the insula and prefrontal cortex and influences a variety of metabolic and cognitive processes [3]. Specifically, I will show that disrupted brain insulin action can result in increased accumulation of visceral fat and altered reward learning in persons at high risk to develop T2D [4], but also in healthy individuals after overconsumption of high caloric foods (unpublished). Moreover, I will show that the effect of intranasal insulin in the hippocampus decreases with age in women but not men and that brain insulin responsivity is affected by the menstrual cycle (unpublished). Moreover, just recently, we could link enhanced brain insulin action in the mesocorticolimbic circuitry with improved cognitive and metabolic functions [5].ConclusionAs brain insulin acts on striatal dopamine function and hippocampal plasticity, enhancing brain insulin action could lead to new treatment options in diabetes and aging‐associated diseases.References1. Hallschmid, M. J Neuroendocrinol, 2021. 33(4): p. e12934.2. Frazier, H.N., et al. Exp Neurol, 2019. 313: p. 79‐87.3. Kullmann, S., et al. Lancet Diabetes Endocrinol, 2020. 8(6): p. 524‐534.4. Kullmann, S., et al. Nat Commun, 2020. 11(1): p. 1841.5. Kullmann, S., et al. JCI Insight, 2022. 7(18).

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Exercise restores brain insulin sensitivity in sedentary adults who are overweight and obese

Cited by 32 publications

References 71 publications

Brain insulin responsiveness is linked to age and peripheral insulin sensitivity

Brain insulin responsiveness is linked to age and peripheral insulin sensitivity

„Ein voller Bauch schläft nicht gut“ – Salutogener Therapieansatz durch Integration der Mayr-Medizin bei Schlafstörungen

Imaging the brain to assess brain insulin action

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