Exercise-Induced Improvements to Whole Body Glucose Metabolism in Type 2 Diabetes: The Essential Role of the Liver

Background: Exercise therapy plays an important role in the prevention and treatment of type 2 diabetes (T2DM). The mechanism of exercise therapy in the improvement of glycolipid metabolism of T2DM is very complex and not completely clear. Summary: Exercise training improves the whole body metabolic health in patients with T2DM, leading to an increase in glycolipid uptake and utilization, improved insulin sensitivity, optimized body mass index, and modulated DNA methylation, etc. Recent findings support that some cytokines such as irisin, osteocalcin, and adiponectin are closely related to exercise and metabolic diseases. This study briefly reviews the physiological mechanisms of exercise therapy in diabetes and the potential role of these cytokines in exercise. Key Messages: More high-quality, targeted, randomized controlled studies are needed urgently, from mechanism study to treatment direction, to provide a more theoretical basis for exercise therapy and to explore new therapeutic targets for diabetes.

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EndoBarrier® in Grade I Obese Patients with Long-Standing Type 2 Diabetes: Role of Gastrointestinal Hormones in Glucose Metabolism

Obesity Surgery ◽

10.1007/s11695-016-2405-8 ◽

2016 ◽

Vol 27 (1) ◽

pp. 194-195 ◽

Cited By ~ 1

Author(s):

Nuria Vilarrasa

Keyword(s):

Type 2 Diabetes ◽

Glucose Metabolism ◽

Gastrointestinal Hormones ◽

Obese Patients

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Role of the renal sympathetic nerve in renal glucose metabolism during the development of type 2 diabetes in rats

Diabetologia ◽

10.1007/s00125-015-3771-9 ◽

2015 ◽

Vol 58 (12) ◽

pp. 2885-2898 ◽

Cited By ~ 28

Author(s):

Kazi Rafiq ◽

Yoshihide Fujisawa ◽

Shamshad J. Sherajee ◽

Asadur Rahman ◽

Abu Sufiun ◽

...

Keyword(s):

Type 2 Diabetes ◽

Glucose Metabolism ◽

Sympathetic Nerve ◽

Renal Sympathetic Nerve ◽

Renal Sympathetic

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Role of Nutrient and Energy Sensors in the Development of Type 2 Diabetes

10.5772/intechopen.95454 ◽

2021 ◽

Author(s):

Verónica Hurtado-Carneiro ◽

Ana Pérez-García ◽

Elvira Álvarez ◽

Carmen Sanz

Keyword(s):

Type 2 Diabetes ◽

Nutrient Availability ◽

Energy Demand ◽

Metabolic Response ◽

Whole Body ◽

Key Factor ◽

Control Food ◽

Control Food Intake

Cell survival depends on the constant challenge to match energy demands with nutrient availability. This process is mediated through a highly conserved network of metabolic fuel sensors that orchestrate both a cellular and whole-body energy balance. A mismatch between cellular energy demand and nutrient availability is a key factor in the development of type 2 diabetes, obesity, metabolic syndrome, and other associated pathologies; thus, understanding the fundamental mechanisms by which cells detect nutrient availability and energy demand may lead to the development of new treatments. This chapter reviews the role of the sensor PASK (protein kinase with PAS domain), analyzing its role in the mechanisms of adaptation to nutrient availability and the metabolic response in different organs (liver, hypothalamus) actively cooperating to control food intake, maintain glycaemia homeostasis, and prevent insulin resistance and weight gain.

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Metabolic Adaptations to Aerobic Exercise in Aged Mice

Innovation in Aging ◽

10.1093/geroni/igab046.2041 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 533-533

Author(s):

Tyler Marx ◽

Anastasiia Vasileva ◽

Stephen Hutchison ◽

Jennifer Stern

Keyword(s):

Type 2 Diabetes ◽

Exercise Training ◽

Aerobic Exercise ◽

Aerobic Exercise Training ◽

Metabolic Function ◽

Glucagon Receptor ◽

Age Related ◽

Exercise Induced

Abstract Aerobic exercise training is a potent intervention for the treatment and prevention of age-related disease, such as heart disease, obesity, and Type 2 Diabetes. Insulin resistance, a hallmark of Type 2 Diabetes, is reversed in response to aerobic exercise training. However, the effect of aerobic exercise training on glucagon sensitivity is unclear. Glucagon signaling at the liver promotes fatty acid oxidation, inhibits De novo lipogenesis, and activates AMP Kinase, a key mediator of healthy aging. Like humans, aging in mice age leads to a decline in physical and metabolic function. To understand the role of glucagon signaling in exercise-induced improvements in physical and metabolic function in the mouse, we implemented a 16-week aerobic exercise training protocol in young and aged mice. 16 weeks of exercise training initiated at 6 months of age increased markers of physical function (P<0.01) and attenuated age-related weight gain (P<0.05) and fat mass (P<0.0001). Additionally, exercise training improved glucose clearance (P<0.01), enhanced glucose-stimulated insulin secretion (P<0.01) and decreased hepatic lipid accumulation (P<0.05). Importantly, exercise training decreased hypoglycemia stimulated glucagon secretion (P<0.01), with no effect on hepatic glucagon receptor mRNA expression or serum glucagon. Thus, we propose that aerobic exercise training enhances glucagon sensitivity at the liver, implicating glucagon as a potential mediator of exercise-induced improvements in aging. Studies initiating the same aerobic exercise training intervention at 18 months of age in the mouse are currently underway to establish the role of glucagon receptor signaling in exercise-induced improvements in aging.

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Attenuation of exercise-induced heat shock protein 72 expression blunts improvements in whole-body insulin resistance in rats with type 2 diabetes

Cell Stress and Chaperones ◽

10.1007/s12192-017-0767-z ◽

2017 ◽

Vol 22 (2) ◽

pp. 263-269 ◽

Cited By ~ 9

Author(s):

Takamasa Tsuzuki ◽

Hiroyuki Kobayashi ◽

Toshinori Yoshihara ◽

Ryo Kakigi ◽

Noriko Ichinoseki-Sekine ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Heat Shock ◽

Heat Shock Protein ◽

Whole Body ◽

Heat Shock Protein 72 ◽

Exercise Induced

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Essential Role of IL-12 in Angiogenesis in Type 2 Diabetes

American Journal Of Pathology ◽

10.1016/j.ajpath.2017.07.021 ◽

2017 ◽

Vol 187 (11) ◽

pp. 2590-2601 ◽

Cited By ~ 12

Author(s):

Maha Ali ◽

Vishal Mali ◽

Samuel Haddox ◽

Soad M. AbdelGhany ◽

Sahar E.M. El-deek ◽

...

Keyword(s):

Type 2 Diabetes ◽

Essential Role

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Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00571.2013 ◽

2014 ◽

Vol 306 (7) ◽

pp. E769-E778 ◽

Cited By ~ 25

Author(s):

N. M. Harder-Lauridsen ◽

R. Krogh-Madsen ◽

J. J. Holst ◽

P. Plomgaard ◽

L. Leick ◽

...

Keyword(s):

Type 2 Diabetes ◽

Glucose Metabolism ◽

Glucose Uptake ◽

Whole Body ◽

Cytokine Signaling ◽

Contributing Factors ◽

Stat3 Phosphorylation ◽

Socs3 Expression ◽

Body Energy

Elevated interleukin-6 (IL-6) levels are associated with type 2 diabetes, but its role in glucose metabolism is controversial. We investigated the effect of IL-6 on insulin-stimulated glucose metabolism in type 2 diabetes patients and hypothesized that an acute, moderate IL-6 elevation would increase the insulin-mediated glucose uptake. Men with type 2 diabetes not treated with insulin [ n = 9, age 54.9 ± 9.7 (mean ± SD) yr, body mass index 34.8 ± 6.1 kg/m2, HbA1c7.0 ± 1.0%] received continuous intravenous infusion with either recombinant human IL-6 (rhIL-6) or placebo. After 1 h with placebo or rhIL-6, a 3-h hyperinsulinemic-isoglycemic clamp was initiated. Whole body glucose metabolism was measured using stable isotope-labeled tracers. Signal transducer and activator of transcription 3 (STAT3) phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression were measured in muscle biopsies. Whole body energy expenditure was measured using indirect calorimetry. In response to the infusion of rhIL-6, circulating levels of IL-6 ( P < 0.001), neutrophils ( P < 0.001), and cortisol ( P < 0.001) increased while lymphocytes decreased ( P < 0.01). However, IL-6 infusion did not change glucose infusion rate, rate of appearance, or rate of disappearance during the clamp. While IL-6 enhanced phosphorylation of STAT3 in skeletal muscle ( P = 0.041), the expression of SOCS3 remained unchanged. Whole body oxygen uptake ( P < 0.01) and expired carbon dioxide ( P < 0.01) increased during rhIL-6 infusion. In summary, although IL-6 induced local and systemic responses, the insulin-stimulated glucose uptake was not affected. While different contributing factors may be involved, our results are in contrast to our hypothesis and previous findings in young, healthy men.

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Astrocyte Clocks and Glucose Homeostasis

Frontiers in Endocrinology ◽

10.3389/fendo.2021.662017 ◽

2021 ◽

Vol 12 ◽

Author(s):

Olga Barca-Mayo ◽

Miguel López

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Glucose Metabolism ◽

Circadian Clock ◽

Glucose Homeostasis ◽

Metabolic Diseases ◽

Current Knowledge ◽

Genetic Alterations ◽

Whole Body

The endogenous timekeeping system evolved to anticipate the time of the day through the 24 hours cycle of the Earth’s rotation. In mammals, the circadian clock governs rhythmic physiological and behavioral processes, including the daily oscillation in glucose metabolism, food intake, energy expenditure, and whole-body insulin sensitivity. The results from a series of studies have demonstrated that environmental or genetic alterations of the circadian cycle in humans and rodents are strongly associated with metabolic diseases such as obesity and type 2 diabetes. Emerging evidence suggests that astrocyte clocks have a crucial role in regulating molecular, physiological, and behavioral circadian rhythms such as glucose metabolism and insulin sensitivity. Given the concurrent high prevalence of type 2 diabetes and circadian disruption, understanding the mechanisms underlying glucose homeostasis regulation by the circadian clock and its dysregulation may improve glycemic control. In this review, we summarize the current knowledge on the tight interconnection between the timekeeping system, glucose homeostasis, and insulin sensitivity. We focus specifically on the involvement of astrocyte clocks, at the organism, cellular, and molecular levels, in the regulation of glucose metabolism.

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