Type 2 diabetes(T2D)is a complex and multifaceted condition clinically characterized by high blood glucose.The management of T2D requires a holistic approach,typically involving a combination of pharmacological interv...Type 2 diabetes(T2D)is a complex and multifaceted condition clinically characterized by high blood glucose.The management of T2D requires a holistic approach,typically involving a combination of pharmacological interventions as well as lifestyle changes,such as incorporating regular exercise,within an overall patient-centred approach.However,several condition-specific and contextual factors can modulate the glucoregulatory response to acute or chronic exercise.In an era of precision medicine,optimizing exercise prescription in an effort to maximize glucose lowering effects holds promise for reducing the risk of T2D complications and improving the overall quality of life of individuals living with this condition.Reflecting on the main pathophysiological features of T2D,we review the evidence to highlight how factors related to exercise prescription can be modulated to target improved glucose control in T2D,including the frequency,intensity,total volume,and timing(e.g.,pre-vs.post-prandial)of exercise,as well as exercise modality(e.g.,aerobic vs.resistance training).We also propose a step-by-step,general framework for clinicians and practitioners on how to personalize exercise prescription to optimize glycemic control in individuals living with T2D.展开更多
Objectives To determine how the anti-inflammatory actions of interleukin-10(IL-10)and IL-6 differ across age and physical activity levels.Methods Using a cross-sectional design,fasted blood samples were obtained from ...Objectives To determine how the anti-inflammatory actions of interleukin-10(IL-10)and IL-6 differ across age and physical activity levels.Methods Using a cross-sectional design,fasted blood samples were obtained from younger physically inactive(YI:n=10,age:22.7±3.7 years,BMI:24.8±4.8 kg/m^(2),<150 min of weekly moderate-to-vigorous physical activity[MVPA]),younger highly active(YA:n=11 varsity cross country running athletes,20.7±2.7 years,21.1±1.8 kg/m^(2),>300 min of weekly MVPA),and older highly active(OA:12,56.0±10.3 years,22.8±3.2 kg/m^(2),>300 min of weekly MVPA)individuals and analyzed for leukocyte counts,IL-10 and IL-6-related signaling,and cytokine secretion ex vivo.Results Total white blood cells and monocytes were similar between groups(p=0.8)but YA and OA had lower lymphocyte counts than YI(p<0.01).The ability of IL-10(1 ng/mL)to phosphorylate signal transducer and activator of transcription 3(STAT3)in CD14 monocytes was greater in YA vs.YI(p<0.03)despite YA having lower IL-10 receptor expression(p<0.01).IL-6(10 ng/mL)mediated STAT3 phosphorylation in CD4 lymphocytes was higher in OA compared YI(p<0.01),with a similar tendency observed for YA vs.YI(p=0.08).Despite enhanced responsiveness of STAT3 to IL-10/6 in active individuals,the ability of IL-10/6 to inhibit tumor necrosis factor-alpha(TNF-⍺)secretion from lipopolysaccharide-stimulated whole-blood was similar between groups.Conclusions Highly active younger and older individuals demonstrate enhanced IL-10-and IL-6-mediated activation of immune cell STAT3.Although the ability of IL-10/6 to inhibit TNF-⍺secretion appeared unimpacted by activity level,anti-inflammatory cytokine actions were preserved in older active individuals.展开更多
Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a ...Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training(HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6(IL-6), and recently identified myokines fibronectin type III domain-containing protein 5(FNDC5)(irisin) and meteorin-like protein(METRNL).Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males(20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise(HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples(vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.Results: Before training, a single bout of HIIE increased IL-6(p < 0.05) and METRNL(p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest(both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training(p < 0.05), and there was an overall increase in FNDC5 mRNA post-training(main effect of training, p < 0.05).Conclusion: In human skeletal muscle(1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT;(2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and(3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.展开更多
Accumulating evidence from epidemiological and experi- mental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive ...Accumulating evidence from epidemiological and experi- mental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive decline （Yates et al., 2012）. The etiology of neurodegeneration in obesity is undoubtedly complex, with vascular, metabolic, inflammatory, and structural changes all likely to play a role （Yates et al., 2012）. The discovery of leptin in 1994 and the subsequent advancement in our understanding that adipose tissue is an endocrine organ that can communicate with the brain to regulate appetite （Zhang et al., 1994） brings about the in- triguing possibility that adipose-brain crosstalk can regulate aspects of neuronal physiology and pathology （Aguilar-Valles et al., 2015）. Indeed neurons have been shown to express receptors for various adipokines, indicating that factors released from adipose tissue have the potential to communi- cate directly with the brain. Research in this area is relatively new, and while epidemiological data points towards the negative consequences of adipose-brain crosstalk （Whitmer et al., 2005）, some intriguing new studies highlight that the secretory profile of adipose tissue might be involved in reduction in neurodegeneration via maintenance of neuronal viability （Tezapsidis et al., 2009; Wan et al., 2015）.展开更多
Aim:Submicron fragments termed microparticles(MPs),derived from all major central nervous system cell types including neurons and glia(microglia,astrocytes,oligodendrocytes),have emerged as novel intercellular signali...Aim:Submicron fragments termed microparticles(MPs),derived from all major central nervous system cell types including neurons and glia(microglia,astrocytes,oligodendrocytes),have emerged as novel intercellular signaling agents.This study tested the hypothesis that MPs derived from activated microglia,which represent the mononuclear phagocyte system in the brain,could induce pro-inflammatory and cytotoxic responses of microglia in an autocrine or paracrine manner.Methods:Human THP-1 monocytic cells were used to model human microglia.MPs derived from these cells were reapplied to THP-1 cells and their secretion of neurotoxins and cytokines was measured.Results:When exposed to lipopolysaccharide(LPS)or mitochondrial transcription factor A in combination with interferon(IFN)-γ,THP-1 cells released MPs.When reapplied to THP-1 cells,MPs induced the release of secretions that were toxic to human SH-SY5Y neuroblastoma cells,as well as monocyte chemoattractant protein-1.The cytotoxicity of THP-1 cells induced by MPs derived from IFN-γplus LPS-treated THP-1 donor cells was enhanced in the presence of IFN-γ.The MPs released by THP-1 cells were not directly toxic towards SH-SY5Y cells.Conclusion:Our data support the hypothesis that activated microglia-derived MPs could act as signaling agents that are recognized by microglia to cause pro-inflammatory and cytotoxic responses.展开更多
文摘Type 2 diabetes(T2D)is a complex and multifaceted condition clinically characterized by high blood glucose.The management of T2D requires a holistic approach,typically involving a combination of pharmacological interventions as well as lifestyle changes,such as incorporating regular exercise,within an overall patient-centred approach.However,several condition-specific and contextual factors can modulate the glucoregulatory response to acute or chronic exercise.In an era of precision medicine,optimizing exercise prescription in an effort to maximize glucose lowering effects holds promise for reducing the risk of T2D complications and improving the overall quality of life of individuals living with this condition.Reflecting on the main pathophysiological features of T2D,we review the evidence to highlight how factors related to exercise prescription can be modulated to target improved glucose control in T2D,including the frequency,intensity,total volume,and timing(e.g.,pre-vs.post-prandial)of exercise,as well as exercise modality(e.g.,aerobic vs.resistance training).We also propose a step-by-step,general framework for clinicians and practitioners on how to personalize exercise prescription to optimize glycemic control in individuals living with T2D.
基金H.I.was supported by a Natural Sciences and Engineering Council(NSERC)postdoctoral fellowship and a Michael Smith Health Research BC Research Trainee AwardJ.B.was supported by and NSERC Undergraduate Student Research Award+2 种基金G.S.J.was supported by an Indigenous Scholar’s AwardJ.P.L is supported by an NSERC Discovery Grant(RGPIN-2019-05204)Killam Accelerator Research Fellowship(AWD-018101).
文摘Objectives To determine how the anti-inflammatory actions of interleukin-10(IL-10)and IL-6 differ across age and physical activity levels.Methods Using a cross-sectional design,fasted blood samples were obtained from younger physically inactive(YI:n=10,age:22.7±3.7 years,BMI:24.8±4.8 kg/m^(2),<150 min of weekly moderate-to-vigorous physical activity[MVPA]),younger highly active(YA:n=11 varsity cross country running athletes,20.7±2.7 years,21.1±1.8 kg/m^(2),>300 min of weekly MVPA),and older highly active(OA:12,56.0±10.3 years,22.8±3.2 kg/m^(2),>300 min of weekly MVPA)individuals and analyzed for leukocyte counts,IL-10 and IL-6-related signaling,and cytokine secretion ex vivo.Results Total white blood cells and monocytes were similar between groups(p=0.8)but YA and OA had lower lymphocyte counts than YI(p<0.01).The ability of IL-10(1 ng/mL)to phosphorylate signal transducer and activator of transcription 3(STAT3)in CD14 monocytes was greater in YA vs.YI(p<0.03)despite YA having lower IL-10 receptor expression(p<0.01).IL-6(10 ng/mL)mediated STAT3 phosphorylation in CD4 lymphocytes was higher in OA compared YI(p<0.01),with a similar tendency observed for YA vs.YI(p=0.08).Despite enhanced responsiveness of STAT3 to IL-10/6 in active individuals,the ability of IL-10/6 to inhibit tumor necrosis factor-alpha(TNF-⍺)secretion from lipopolysaccharide-stimulated whole-blood was similar between groups.Conclusions Highly active younger and older individuals demonstrate enhanced IL-10-and IL-6-mediated activation of immune cell STAT3.Although the ability of IL-10/6 to inhibit TNF-⍺secretion appeared unimpacted by activity level,anti-inflammatory cytokine actions were preserved in older active individuals.
基金supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (No. RGPIN 435807-13) to JPLthe ANZ-MASON foundation (to DB)supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award (No. MSH-141980)
文摘Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training(HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6(IL-6), and recently identified myokines fibronectin type III domain-containing protein 5(FNDC5)(irisin) and meteorin-like protein(METRNL).Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males(20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise(HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples(vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.Results: Before training, a single bout of HIIE increased IL-6(p < 0.05) and METRNL(p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest(both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training(p < 0.05), and there was an overall increase in FNDC5 mRNA post-training(main effect of training, p < 0.05).Conclusion: In human skeletal muscle(1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT;(2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and(3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.
文摘Accumulating evidence from epidemiological and experi- mental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive decline （Yates et al., 2012）. The etiology of neurodegeneration in obesity is undoubtedly complex, with vascular, metabolic, inflammatory, and structural changes all likely to play a role （Yates et al., 2012）. The discovery of leptin in 1994 and the subsequent advancement in our understanding that adipose tissue is an endocrine organ that can communicate with the brain to regulate appetite （Zhang et al., 1994） brings about the in- triguing possibility that adipose-brain crosstalk can regulate aspects of neuronal physiology and pathology （Aguilar-Valles et al., 2015）. Indeed neurons have been shown to express receptors for various adipokines, indicating that factors released from adipose tissue have the potential to communi- cate directly with the brain. Research in this area is relatively new, and while epidemiological data points towards the negative consequences of adipose-brain crosstalk （Whitmer et al., 2005）, some intriguing new studies highlight that the secretory profile of adipose tissue might be involved in reduction in neurodegeneration via maintenance of neuronal viability （Tezapsidis et al., 2009; Wan et al., 2015）.
基金supported by grants from the Jack Brown and Family Alzheimer’s Disease Research Foundation,the Natural Sciences and Engineering Research Council of Canada,and the University of British Columbia Okanagan Campus.
文摘Aim:Submicron fragments termed microparticles(MPs),derived from all major central nervous system cell types including neurons and glia(microglia,astrocytes,oligodendrocytes),have emerged as novel intercellular signaling agents.This study tested the hypothesis that MPs derived from activated microglia,which represent the mononuclear phagocyte system in the brain,could induce pro-inflammatory and cytotoxic responses of microglia in an autocrine or paracrine manner.Methods:Human THP-1 monocytic cells were used to model human microglia.MPs derived from these cells were reapplied to THP-1 cells and their secretion of neurotoxins and cytokines was measured.Results:When exposed to lipopolysaccharide(LPS)or mitochondrial transcription factor A in combination with interferon(IFN)-γ,THP-1 cells released MPs.When reapplied to THP-1 cells,MPs induced the release of secretions that were toxic to human SH-SY5Y neuroblastoma cells,as well as monocyte chemoattractant protein-1.The cytotoxicity of THP-1 cells induced by MPs derived from IFN-γplus LPS-treated THP-1 donor cells was enhanced in the presence of IFN-γ.The MPs released by THP-1 cells were not directly toxic towards SH-SY5Y cells.Conclusion:Our data support the hypothesis that activated microglia-derived MPs could act as signaling agents that are recognized by microglia to cause pro-inflammatory and cytotoxic responses.
