Hyperglycemia and type 2 diabetes : impact on neural cardiovascular control

2015 ◽  
Author(s):  
◽  
Seth H. Holwerda
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Muscle Sympathetic Nerve Activity ◽  
Muscle Afferents ◽  
Chronic Hypertension ◽  
University Of Missouri ◽  
Arterial Blood

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Type 2 diabetes (T2D) is often characterized by chronic hypertension and exaggerated increases in arterial blood pressure (BP) during exercise. However, investigations of the neural mechanisms that are known to be critically involved in BP regulation at rest and during exercise in T2D have been lacking. Also, hyperglycemia decreases arterial baroreflex (ABR) control of heart rate (HR) in conditions of reduced insulin sensitivity, but whether hyperglycemia reduces ABR control of HR in healthy subjects has not been investigated. In study #1, findings demonstrated that ABR control of HR is reduced following acute hyperglycemia in healthy subjects independent of insulin sensitivity, and also during hyperinsulinemia. Study #2 focused on ABR control of HR and muscle sympathetic nerve activity (MSNA) in T2D patients, which are chronically hyperglycemic and hyperinsulinemic. No differences in ABR control of MSNA were observed; however, ABR control of HR was significantly reduced in T2D patients compared to lean controls, but not weight-matched (i.e., obese) controls. These findings suggest a potential selective impairment in ABR control of HR in T2D that may be a consequence of obesity. Finally, given the exaggerated BP responses to exercise in T2D patients, and the vital contribution of skeletal muscle neural feedback to the BP responses to exercise, study #3 focused on BP and MSNA responses to activation of skeletal muscle neural afferents in T2D patients. The findings demonstrated that BP and MSNA responses to activation of skeletal muscle afferents sensitive to muscle metabolites was augmented in T2D patients.

Insulin sensitivity and big ET-1 conversion to ET-1 after ETA- or ETB-receptor blockade in humans

2002 ◽  
Vol 93 (6) ◽  
pp. 2112-2121 ◽  
Author(s):  
Gunvor Ahlborg ◽  
Jonas Lindström
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Receptor Blockade ◽  
Receptor Stimulation ◽  
Renal Vasoconstriction ◽  
Arterial Blood ◽  
Etb Receptor

Cardiovascular diseases are characterized by insulin resistance and elevated endothelin (ET)-1 levels. Furthermore, ET-1 induces insulin resistance. To elucidate this mechanism, six healthy subjects were studied during a hyperinsulinemic euglycemic clamp during infusion of (the ET-1 precursor) big ET-1 alone or after ETA- or ETB-receptor blockade. Insulin levels rose after big ET-1 with or without the ETB antagonist BQ-788 ( P < 0.05) but were unchanged after the ETA antagonist BQ-123 + big ET-1. Infused glucose divided by insulin fell after big ET-1 with or without BQ-788 ( P < 0.05). Insulin and infused glucose divided by insulin values were normalized by ETA blockade. Mean arterial blood pressure rose during big ET-1 with or without BQ-788 ( P < 0.001) but was unchanged after BQ-123. Skeletal muscle, splanchnic, and renal blood flow responses to big ET-1 were abolished by BQ-123. ET-1 levels rose after big ET-1 ( P< 0.01) in a similar way after BQ-123 or BQ-788, despite higher elimination capacity after ETA blockade. In conclusion, ET-1-induced reduction in insulin sensitivity and clearance as well as splanchnic and renal vasoconstriction are ETA mediated. ETA-receptor stimulation seems to inhibit the conversion of big ET-1 to ET-1.

scholarly journals Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity

Diabetologia ◽  
2020 ◽  
Author(s):  
Alexandre Houzelle ◽  
Johanna A. Jörgensen ◽  
Gert Schaart ◽  
Sabine Daemen ◽  
Nynke van Polanen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Quality Control ◽  
Insulin Sensitivity ◽  
Aerobic Capacity ◽  
Mitochondrial Dynamics ◽  
Oxidative Capacity ◽  
Protein Balance ◽  
Diabetes Patients

Abstract Aims/hypothesis Mitochondria operate in networks, adapting to external stresses and changes in cellular metabolic demand and are subject to various quality control mechanisms. On the basis of these traits, we here hypothesise that the regulation of mitochondrial networks in skeletal muscle is hampered in humans with compromised oxidative capacity and insulin sensitivity. Methods In a cross-sectional design, we compared four groups of participants (selected from previous studies) ranging in aerobic capacity and insulin sensitivity, i.e. participants with type 2 diabetes (n = 11), obese participants without diabetes (n = 12), lean individuals (n = 10) and endurance-trained athletes (n = 12); basal, overnight fasted muscle biopsies were newly analysed for the current study and we compared the levels of essential mitochondrial dynamics and quality control regulatory proteins in skeletal muscle tissue. Results Type 2 diabetes patients and obese participants were older than lean participants and athletes (58.6 ± 4.0 and 56.7 ± 7.2 vs 21.8 ± 2.5 and 25.1 ± 4.3 years, p < 0.001, respectively) and displayed a higher BMI (32.4 ± 3.7 and 31.0 ± 3.7 vs 22.1 ± 1.8 and 21.0 ± 1.5 kg/m2, p < 0.001, respectively) than lean individuals and endurance-trained athletes. Fission protein 1 (FIS1) and optic atrophy protein 1 (OPA1) protein content was highest in muscle from athletes and lowest in participants with type 2 diabetes and obesity, respectively (FIS1: 1.86 ± 0.79 vs 0.79 ± 0.51 AU, p = 0.002; and OPA1: 1.55 ± 0.64 vs 0.76 ± 0.52 AU, p = 0.014), which coincided with mitochondrial network fragmentation in individuals with type 2 diabetes, as assessed by confocal microscopy in a subset of type 2 diabetes patients vs endurance-trained athletes (n = 6). Furthermore, lean individuals and athletes displayed a mitonuclear protein balance that was different from obese participants and those with type 2 diabetes. Mitonuclear protein balance also associated with heat shock protein 60 (HSP60) protein levels, which were higher in athletes when compared with participants with obesity (p = 0.048) and type 2 diabetes (p = 0.002), indicative for activation of the mitochondrial unfolded protein response. Finally, OPA1, FIS1 and HSP60 correlated positively with aerobic capacity (r = 0.48, p = 0.0001; r = 0.55, p < 0.001 and r = 0.61, p < 0.0001, respectively) and insulin sensitivity (r = 0.40, p = 0.008; r = 0.44, p = 0.003 and r = 0.48, p = 0.001, respectively). Conclusions/interpretation Collectively, our data suggest that mitochondrial dynamics and quality control in skeletal muscle are linked to oxidative capacity in humans, which may play a role in the maintenance of muscle insulin sensitivity. Clinical Trial registry numbers NCT00943059, NCT01298375 and NL1888

scholarly journals Exercise Response Variations in Skeletal Muscle PCr Recovery Rate and Insulin Sensitivity Relate to Muscle Epigenomic Profiles in Individuals With Type 2 Diabetes

Diabetes Care ◽  
2018 ◽  
Vol 41 (10) ◽  
pp. 2245-2254 ◽  
Author(s):  
Natalie A. Stephens ◽  
Bram Brouwers ◽  
Alexey M. Eroshkin ◽  
Fanchao Yi ◽  
Heather H. Cornnell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Recovery Rate ◽  
Exercise Response

scholarly journals Plasma FGF-21 and Sclerostin Levels, Glycemia, Adiposity and Insulin Sensitivity in Normoglycemic Black and White Adults

2021 ◽  
Author(s):  
Nkiru Umekwe ◽  
Ibiye Owei ◽  
Frankie Stentz ◽  
Sam Dagogo-Jack
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Fibroblast Growth ◽  
Black And White ◽  
Fasting Plasma ◽  
White Adults

Abstract Increased circulating fibroblast growth factor (FGF)-21 and sclerostin levels have been reported in patients with type 2 diabetes (T2D). We assessed the association of FGF-21 and sclerostin with adiposity, glycemia and glucoregulatory measures in healthy subjects. We studied 20 normoglycemic Black and White offspring of parents with T2D. Assessments included OGTT, insulin sensitivity (Si-clamp), insulin secretion (HOMA-B), and body fat (DXA). Fasting plasma FGF-21 and sclerostin levels were measured with ELISAs. The participants' mean (+SD) age was 50.4 ± 5.97 yr; BMI 32.5 ± 5.86 kg/m2; fasting plasma glucose (FPG) 96.1 ± 5.21 mg/dl, and 2-hr post-load glucose (2hPG) 116 ± 5.45 mg/dl. FGF-21 levels were similar in Blacks vs. Whites (0.36 ± 0.15 ng/ml vs. 0.39 ± 0.25 ng/ml), men vs. women (0.45 ± 0.14 vs. 0.44 ± 0.07ng/ml), correlated positively with body mass index (BMI) (r=0.23, P=0.05) and waist circumference (r=0.27, P=0.04), and inversely with FPG (r= -0.26, P=0.05). Sclerostin levels also were similar in Blacks (33.5 ± 17.1 pmol/l) vs. Whites (34.2 ± 6.41 pmol/l), men vs. women (35.3 ± 9.01 pmol/l vs. 32.3 ± 15.8 pmol/l), and correlated inversely with FPG (r= - 0.11-0.44) but not adiposity measures. The correlation coefficient between Si-clamp values and FGF-21 levels was -0.31 (P=0.09) compared with 0.04 (P=0.89) for sclerostin levels. FGF-21 and sclerostin levels were not correlated with each other or HOMA-B. Among healthy Black and White subjects, plasma FGF-21 and sclerostin showed differential associations with adiposity but concordant association with FPG levels.

Hypoglycaemic effect of catalpol in a mouse model of high-fat diet-induced prediabetes

2020 ◽  
Vol 45 (10) ◽  
pp. 1127-1137 ◽  
Author(s):  
Dengqiu Xu ◽  
Xiaofei Huang ◽  
Hozeifa M. Hassan ◽  
Lu Wang ◽  
Sijia Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Fasting Glucose ◽  
Hypoglycaemic Effect

Type 2 diabetes mellitus is a major health problem and a societal burden. Individuals with prediabetes are at increased risk of type 2 diabetes mellitus. Catalpol, an iridoid glycoside, has been reported to exert a hypoglycaemic effect in db/db mice, but its effect on the progression of prediabetes is unclear. In this study, we established a mouse model of prediabetes and examined the hypoglycaemic effect, and the mechanism of any such effect, of catalpol. Catalpol (200 mg/(kg·day)) had no effect on glucose tolerance or the serum lipid level in a mouse model of impaired glucose tolerance-stage prediabetes. However, catalpol (200 mg/(kg·day)) increased insulin sensitivity and decreased the fasting glucose level in a mouse model of impaired fasting glucose/impaired glucose tolerance-stage prediabetes. Moreover, catalpol increased the mitochondrial membrane potential (1.52-fold) and adenosine triphosphate content (1.87-fold) in skeletal muscle and improved skeletal muscle function. These effects were mediated by activation of the insulin receptor-1/glucose transporter type 4 (IRS-1/GLUT4) signalling pathway in skeletal muscle. Our findings will facilitate the development of a novel approach to suppressing the progression of diabetes at an early stage. Novelty Catalpol prevents the progression of prediabetes in a mouse model of prediabetes. Catalpol improves insulin sensitivity in skeletal muscle. The effects of catalpol are mediated by activation of the IRS-1/GLUT4 signalling pathway.

Sympathetic Activation due to Limb Venous Distension Is Preserved during Muscle Metaboreceptor Stimulation

2021 ◽  
Author(s):  
Jian Cui ◽  
Cheryl Blaha ◽  
Urs A. Leuenberger ◽  
Lawrence I. Sinoway
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Healthy Subjects ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Muscle Afferents ◽  
Sympathetic Activation ◽  
Nerve Activity ◽  
Post Exercise ◽  
Muscle Metaboreflex

Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in humans (venous distension reflex). It is unclear if the inputs from metabolically sensitive skeletal muscle afferents (i.e. muscle metaboreflex) would modify venous distension reflex. We hypothesized that muscle metaboreceptor stimulation might augment the venous distension reflex. BP (Finapres), heart rate (ECG), and MSNA (microneurography) were assessed in 18 young healthy subjects. In trial A, saline (5% forearm volume) was infused into the veins of an arterially occluded arm (non-handgrip trial). In trial B, subjects performed 2 min static handgrip followed by post exercise circulatory occlusion (PECO) of the arm. During PECO, saline was infused into veins of the arm (handgrip trial). In trial A, the infusion increased MSNA and BP as expected (both P < 0.001). In trial B, handgrip significantly raised MSNA, BP and venous lactic acid concentrations. Venous saline infusion during PECO further raised MSNA and BP (both P < 0.001). The changes in MSNA (D8.6 ± 1.5 to D10.6 ± 1.8 bursts/min, P = 0.258) and mean arterial pressure (P = 0.844) evoked by the infusion during PECO were not significantly different from those in the non-handgrip trial. These observations indicate that venous distension reflex responses are preserved during sympathetic activation mediated by the muscle metaboreflex.

scholarly journals Leptin Enhances Insulin Sensitivity by Direct and Sympathetic Nervous System Regulation of Muscle IGFBP-2 Expression: Evidence From Nonrodent Models

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2133-2143 ◽  
Author(s):  
Steven W. Yau ◽  
Belinda A. Henry ◽  
Vincenzo C. Russo ◽  
Glenn K. McConell ◽  
Iain J. Clarke ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Nervous System ◽  
Insulin Sensitivity ◽  
Sympathetic Nervous System ◽  
Insulin Signaling ◽  
In Vivo Experiments ◽  
Sympathetic Nervous

Leptin is produced from white adipose tissue and acts primarily to regulate energy balance. Obesity is associated with leptin resistance and increased circulating levels of leptin. Leptin has recently been shown to influence levels of IGF binding protein-2 (IGFBP-2), a protein that is reduced in obesity and type 2 diabetes. Overexpression of IGFBP-2 protects against obesity and type 2 diabetes. As such, IGFBP-2 signaling may represent a novel pathway by which leptin regulates insulin sensitivity. We sought to investigate how leptin regulates skeletal muscle IGFBP-2 levels and to assess the impact of this on insulin signaling and glucose uptake. In vitro experiments were undertaken in cultured human skeletal myotubes, whereas in vivo experiments assessed the effect of intracerebroventricular leptin on peripheral skeletal muscle IGFBP-2 expression and insulin sensitivity in sheep. Leptin directly increased IGFBP-2 mRNA and protein in human skeletal muscle through both signal transducer and activator of transcription-3 and phosphatidylinositol 3-kinase signaling, in parallel with enhanced insulin signaling. Silencing IGFBP-2 lowered leptin- and insulin-stimulated protein kinase B phosphorylation and glucose uptake. In in vivo experiments, intracerebroventricular leptin significantly increased hind-limb skeletal muscle IGFBP-2, an effect completely blocked by concurrent peripheral infusion of a β-adrenergic blocking agent. Sheep receiving central leptin showed improvements in glucose tolerance and circulating insulin levels after an iv glucose load. In summary, leptin regulates skeletal muscle IGFBP-2 by both direct peripheral and central (via the sympathetic nervous system) mechanisms, and these likely impact on peripheral insulin sensitivity and glucose metabolism.

scholarly journals Impact of Endurance and Resistance Training on Skeletal Muscle Glucose Metabolism in Older Adults

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2636 ◽  
Author(s):  
Leslie A. Consitt ◽  
Courtney Dudley ◽  
Gunjan Saxena
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Older Adults ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Resistance Training ◽  
Glucose Metabolism ◽  
Age Related ◽  
Age Related Changes

Aging is associated with insulin resistance and the development of type 2 diabetes. While this process is multifaceted, age-related changes to skeletal muscle are expected to contribute to impaired glucose metabolism. Some of these changes include sarcopenia, impaired insulin signaling, and imbalances in glucose utilization. Endurance and resistance exercise training have been endorsed as interventions to improve glucose tolerance and whole-body insulin sensitivity in the elderly. While both types of exercise generally increase insulin sensitivity in older adults, the metabolic pathways through which this occurs can differ and can be dependent on preexisting conditions including obesity and type 2 diabetes. In this review, we will first highlight age-related changes to skeletal muscle which can contribute to insulin resistance, followed by a comparison of endurance and resistance training adaptations to insulin-stimulated glucose metabolism in older adults.

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