scholarly journals Insulin-mediated muscle microvascular perfusion and its phenotypic predictors in humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaitlin M. Love ◽  
Linda A. Jahn ◽  
Lee M. Hartline ◽  
James T. Patrie ◽  
Eugene J. Barrett ◽  
...  
Keyword(s):  
Body Mass ◽  
Hdl Cholesterol ◽  
Total Body Weight ◽  
Microvascular Perfusion ◽  
Whole Body ◽  
Glucose Disposal ◽  
Phenotypic Traits ◽  
Predictive Information ◽  
Class 1 ◽  
Insulin Responses

AbstractInsulin increases muscle microvascular perfusion and enhances tissue insulin and nutrient delivery. Our aim was to determine phenotypic traits that foretell human muscle microvascular insulin responses. Hyperinsulinemic euglycemic clamps were performed in 97 adult humans who were lean and healthy, had class 1 obesity without comorbidities, or controlled type 1 diabetes without complications. Insulin-mediated whole-body glucose disposal rates (M-value) and insulin-induced changes in muscle microvascular blood volume (ΔMBV) were determined. Univariate and multivariate analyses were conducted to examine bivariate and multivariate relationships between outcomes, ΔMBV and M-value, and predictor variables, body mass index (BMI), total body weight (WT), percent body fat (BF), lean body mass, blood pressure, maximum consumption of oxygen (VO2max), plasma LDL (LDL-C) and HDL cholesterol, triglycerides (TG), and fasting insulin (INS) levels. Among all factors, only M-value (r = 0.23, p = 0.02) and VO2max (r = 0.20, p = 0.047) correlated with ΔMBV. Conversely, INS (r = − 0.48, p ≤ 0.0001), BF (r = − 0.54, p ≤ 0.001), VO2max (r = 0.5, p ≤ 0.001), BMI (r = − 0.40, p < 0.001), WT (r = − 0.33, p = 0.001), LDL-C (r = − 0.26, p = 0.009), TG (r = − 0.25, p = 0.012) correlated with M-value. While both ΔMBV (p = 0.045) and TG (p = 0.03) provided significant predictive information about M-value in the multivariate regression model, only M-value was uniquely predictive of ΔMBV (p = 0.045). Thus, both M-value and VO2max correlated with ΔMBV but only M-value provided unique predictive information about ΔMBV. This suggests that metabolic and microvascular insulin responses are important predictors of one another, but most metabolic insulin resistance predictors do not predict microvascular insulin responses.

scholarly journals Effect of gender on lipid-induced insulin resistance in obese subjects

2008 ◽  
Vol 158 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Bodil Vistisen ◽  
Lars I Hellgren ◽  
Torill Vadset ◽  
Celena Scheede-Bergdahl ◽  
Jørn Wulff Helge ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Glucose Disposal ◽  
Muscle Lipid ◽  
Obese Subjects ◽  
Skeletal Muscle Insulin Sensitivity

ObjectiveIn obese subjects, chronically elevated plasma concentrations of non-esterified fatty acids (NEFAs) exert a marked risk to contract insulin resistance and subsequently type 2 diabetes. When NEFA is acutely increased due to i.v. infusion of lipid, glucose disposal during a hyperinsulinemic–euglycemic clamp is reduced. This effect has been explained by a NEFA-induced decrease in skeletal muscle insulin sensitivity caused by accumulation of the lipid intermediates such as ceramide and diacylglycerol in the myocytes. However, neither the lipid-induced reduction of glucose disposal nor the intramyocellular lipid deposition has been compared directly in obese females and males.DesignWe studied eight obese females and eight obese males (body mass index (BMI): 32.6±1.4 and 32.8±0.8 respectively, non significant (NS)) matched for cardiorespiratory fitness relative to lean body mass (43.7±1.6 and 47.6±1.3 ml/kg min respectively, NS).MethodsEach subject underwent two hyperinsulinemic–euglycemic clamps with infusion of lipid or saline respectively. Furthermore, the subjects exercised during the last half an hour of each clamp.ResultsThe lipid-induced reduction in glucose disposal during the clamp was similar in females and males (46±10 and 60±4% respectively, NS). However, whole-body insulin sensitivity as well as non-oxidative glucose disposal was higher in obese females compared with obese males both during lipid and saline infusion (P<0.001 andP=0.01 respectively). Muscle ceramide, triacylglycerol (TAG), diacylglycerol (DAG), and glycogen content were similar between sexes and remained unchanged during the clamp and when exercise was superimposed.ConclusionsThe lipid-induced inhibition of glucose disposal is similar in obese females and males. However, obese females are more insulin sensitive compared with obese males (both during saline and lipid infusion), which is not due to differences in the concentration of the muscle lipid intermediates such as ceramide and DAG.

scholarly journals Effects of a Single Exercise Bout on Insulin Sensitivity in Black and White Individuals

2010 ◽  
Vol 95 (10) ◽  
pp. E219-E223 ◽  
Author(s):  
Rebecca E. Hasson ◽  
Kirsten Granados ◽  
Stuart Chipkin ◽  
Patty S. Freedson ◽  
Barry Braun
Keyword(s):  
Body Mass Index ◽  
Insulin Sensitivity ◽  
Racial Differences ◽  
Body Mass ◽  
Glucose Oxidation ◽  
Exercise Bout ◽  
Whole Body ◽  
Glucose Disposal ◽  
Maximal Heart Rate ◽  
Glucose Storage

Background: Previous research suggests non-Hispanic blacks (blacks) are more insulin resistant than non-Hispanic whites (whites). Physical activity can play an important role in reducing insulin resistance. However, it is unknown whether racial differences exist in response to exercise. Therefore, the purpose of this study was to compare metabolic responses to a single bout of exercise in blacks and age-, sex-, and body mass index-matched whites. Methods: Whole-body insulin sensitivity, glucose storage, glucose oxidation, and respiratory exchange ratio (RER) were assessed during a hyperinsulinemic-euglycemic clamp in normoglycemic blacks (n = 11) and whites (n = 10). Outcome measures were evaluated in a sedentary control condition and 12 h after treadmill walking at 75% of maximal heart rate for 75 min. Results: In the control condition, there were no differences in insulin sensitivity between blacks and whites (P = 0.54). During the clamp, glucose oxidation and insulin-stimulated RER values were significantly higher in blacks compared with whites (P = 0.04 and P &lt; 0.01, respectively). Despite similar RER values during exercise, RER values at 60, 90, and 120 min after exercise in blacks were also significantly higher compared with whites (P &lt; 0.05). After exercise, there were no significant improvements in insulin sensitivity (P = 0.57) or glucose storage (P = 0.42) in blacks or whites; however, glucose oxidation was significantly lower in both racial groups (P &lt; 0.05). Conclusions: These data suggest that insulin sensitivity is similar in blacks and age-, sex-, and body mass index-matched whites, but the glucose disposal pathways (storage vs. oxidation) are somewhat different. Compared with whites, blacks appear to have a greater capacity to increase glucose oxidation immediately after exercise and during insulin stimulation.

scholarly journals Losartan increases muscle insulin delivery and rescues insulin's metabolic action during lipid infusion via microvascular recruitment

2013 ◽  
Vol 304 (5) ◽  
pp. E538-E545 ◽  
Author(s):  
Nasui Wang ◽  
Weidong Chai ◽  
Lina Zhao ◽  
Lijian Tao ◽  
Wenhong Cao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Angiotensin Ii ◽  
Insulin Delivery ◽  
Microvascular Perfusion ◽  
Whole Body ◽  
Glucose Disposal ◽  
Lipid Infusion ◽  
Metabolic Action ◽  
Microvascular Recruitment ◽  
Insulin Uptake

Insulin delivery and transendothelial insulin transport are two discrete steps that limit muscle insulin action. Angiotensin II type 1 receptor (AT1R) blockade recruits microvasculature and increases glucose use in muscle. Increased muscle microvascular perfusion is associated with increased muscle delivery and action of insulin. To examine the effect of acute AT1R blockade on muscle insulin uptake and action, rats were studied after an overnight fast to examine the effects of losartan on muscle insulin uptake ( protocol 1), microvascular perfusion ( protocol 2), and insulin's microvascular and metabolic actions in the state of insulin resistance ( protocol 3). Endothelial cell insulin uptake was assessed, using 125I-insulin as tracer. Systemic lipid infusion was used to induce insulin resistance. Losartan significantly increased muscle insulin uptake (∼60%, P < 0.03), which was associated with a two- to threefold increase in muscle microvascular blood volume (MBV; P = 0.002) and flow (MBF; P = 0.002). Losartan ± angiotensin II had no effect on insulin internalization in cultured endothelial cells. Lipid infusion abolished insulin-mediated increases in muscle MBV and MBF and lowered insulin-stimulated whole body glucose disposal ( P = 0.0001), which were reversed by losartan administration. Inhibition of nitric oxide synthase abolished losartan-induced muscle insulin uptake and reversal of lipid-induced metabolic insulin resistance. We conclude that AT1R blockade increases muscle insulin uptake mainly via microvascular recruitment and rescues insulin's metabolic action in the insulin-resistant state. This may contribute to the clinical findings of decreased cardiovascular events and new onset of diabetes in patients receiving AT1R blockers.

Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans

2007 ◽  
Vol 293 (5) ◽  
pp. E1393-E1398 ◽  
Author(s):  
Marietta Anderwald-Stadler ◽  
Michael Krebs ◽  
Miriam Promintzer ◽  
Martina Mandl ◽  
Martin G. Bischof ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Infusion ◽  
Plasma Concentrations ◽  
Hdl Cholesterol ◽  
Whole Body ◽  
Glucose Disposal ◽  
Insulin Resistant ◽  
Amino Acid Peptide ◽  
Fasting Plasma ◽  
Precursor Peptide

Obestatin, a recently discovered 23-amino acid peptide, is involved in the regulation of appetite and body weight in antagonistic fashion to ghrelin, both deriving from a common precursor peptide. Ghrelin was shown to be associated with insulin resistance, which may also affect obestatin. We investigated the association between insulin resistance and plasma concentrations of obestatin and ghrelin in nondiabetic individuals with high (IS; n = 18, 13 females and 5 males, age 47 ± 2 yr, BMI = 25.5 ± 0.9 kg/m2) and low (IR; n = 18, 12 females and 6 males, age 45 ± 2 yr, P = 0.49, BMI = 27.5 ± 1.1 kg/m2, P = 0.17) insulin-stimulated glucose disposal (M), measured by 2-h hyperinsulinemic (40 mU·min−1·m−2) isoglycemic clamp tests. M100–120 min was higher in IS (10.7 ± 0.7) than in IR (4.4 ± 0.2 mg·min−1·kg−1, P < 10−9), whereas insulin-dependent suppression of free fatty acids (FFA) in plasma was reduced in IR (71 ± 6% vs. IS: 82 ± 5%, P < 0.02). In both groups, plasma ghrelin concentrations were comparable at fasting and similarly reduced by 24–28% during insulin infusion. IR had lower fasting plasma obestatin levels (383 ± 26 pg/ml vs. IS: 469 ± 23 pg/ml, P < 0.02). Clamp insulin infusion reduced plasma obestatin to ∼81% of basal values in IS ( P < 0.00002), but not in IR. Fasting plasma obestatin was correlated positively with M ( r = 0.34, P = 0.04), HDL cholesterol ( r = 0.45, P = 0.01), and plasma ghrelin concentrations ( r = 0.80, P < 0.000001) and negatively with measures of adiposity, plasma FFA during clamp ( r = −0.42, P < 0.01), and systolic blood pressure ( r = −0.33, P < 0.05). In conclusion, fasting plasma concentrations of obestatin, but not of ghrelin, are reduced in insulin resistance and are positively associated with whole body insulin sensitivity in nondiabetic humans. Furthermore, plasma obestatin is reduced by insulin in insulin-sensitive but not in insulin-resistant persons.

Abstract 308: Losartan Increases Muscle Insulin Delivery via Microvascular Recruitment and Rescues Insulin’s Metabolic Action during Lipid Infusion

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Nasui Wang ◽  
Weidong Chai ◽  
Lina Zhao ◽  
Zhenqi Liu
Keyword(s):  
Insulin Resistance ◽  
Angiotensin Ii ◽  
Insulin Delivery ◽  
Microvascular Perfusion ◽  
Whole Body ◽  
Glucose Disposal ◽  
Lipid Infusion ◽  
Metabolic Action ◽  
Microvascular Recruitment ◽  
Insulin Uptake

Rationale: Insulin delivery and transendothelial insulin transport are two discrete steps that limit muscle insulin action. Angiotensin II type 1 receptor (AT 1 R) blockade recruits microvasculature and increases glucose use in muscle. Increased muscle microvascular perfusion is associated with increased muscle delivery and action of insulin. Objective: To examine the effect of acute AT 1 R blockade on muscle insulin uptake and action in rats. Methods and Results: Rats were studied after an overnight fast to examine the effects of losartan on muscle insulin uptake (protocol 1), microvascular perfusion (protocol 2), and insulin’s microvascular and metabolic actions in the state of insulin resistance (protocol 3). Endothelial cell insulin uptake was assessed using 125 I-insulin as tracer. Systemic lipid infusion was used to induce insulin resistance. Losartan significantly increased muscle insulin uptake (∼60%, p<0.03), which was associated with 2-3-fold increase in muscle microvascular blood volume (MBV, p=0.002) and flow (MBF, p=0.002). Losartan ± angiotensin II had no effect on insulin internalization in cultured endothelial cells. Lipid infusion abolished insulin-mediated increases in muscle MBV and MBF, and lowered insulin-stimulated whole body glucose disposal (p=0.0001) which were reversed by losartan administration. Inhibition of nitric oxide synthase abolished losartan-induced muscle insulin uptake and reversal of lipid-induced metabolic insulin resistance. Conclusion: AT 1 R blockade increases muscle insulin uptake mainly via microvascular recruitment and rescues insulin’s metabolic action in the insulin resistant state. This may contribute to the clinical findings of decreased cardiovascular events and new onset of diabetes in patients receiving AT 1 R blockers.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

scholarly journals Contributions of source population and incubation temperature to phenotypic variation of hatchling Chinese skinks

2020 ◽  
Author(s):  
Hong-Liang Lu ◽  
Yan-Fu Qu ◽  
Hong Li ◽  
Xiang Ji
Keyword(s):  
Body Mass ◽  
Phenotypic Variation ◽  
Incubation Temperature ◽  
Tail Length ◽  
Population Variation ◽  
Phenotypic Traits ◽  
Source Population ◽  
Relative Importance ◽  
The Difference ◽  
Hatchling Size

Abstract Phenotypic plasticity and local adaptation are viewed as the main factors that result in between-population variation in phenotypic traits, but contributions of these factors to phenotypic variation vary between traits and between species and have only been explored in a few species of reptiles. Here, we incubated eggs of the Chinese skink (Plestiodon chinensis) from 7 geographically separated populations in Southeast China at 3 constant temperatures (24, 28, and 32 °C) to evaluate the combined effects of clutch origin, source population, and incubation temperature on hatchling traits. The relative importance of these factors varied between traits. Nearly all examined hatchling traits, including body mass, snout–vent length (SVL), tail length, head size, limb length, tympanum diameter, and locomotor speed, varied among populations and were affected by incubation temperature. Measures for hatchling size (body mass and SVL) varied considerably among clutches. Source population explained much of the variation in hatchling body mass, whereas incubation temperature explained much of the variation in other examined traits. Our results indicate that between-population variation in hatchling traits of P. chinensis likely reflects the difference in natural incubation conditions and genetic divergence.

scholarly journals A method for evaluation of patient-specific lean body mass from limited-coverage CT images and its application in PERCIST: comparison with predictive equation

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jingjie Shang ◽  
Zhiqiang Tan ◽  
Yong Cheng ◽  
Yongjin Tang ◽  
Bin Guo ◽  
...  
Keyword(s):  
Lean Body Mass ◽  
Body Mass ◽  
Whole Body ◽  
Patient Specific ◽  
Predictive Equation ◽  
Reference Standard ◽  
Pet Ct ◽  
Before And After ◽  
Percist 1.0 ◽  
Limited Coverage

Abstract Background Standardized uptake value (SUV) normalized by lean body mass ([LBM] SUL) is recommended as metric by PERCIST 1.0. The James predictive equation (PE) is a frequently used formula for LBM estimation, but may cause substantial error for an individual. The purpose of this study was to introduce a novel and reliable method for estimating LBM by limited-coverage (LC) CT images from PET/CT examinations and test its validity, then to analyse whether SUV normalised by LC-based LBM could change the PERCIST 1.0 response classifications, based on LBM estimated by the James PE. Methods First, 199 patients who received whole-body PET/CT examinations were retrospectively retrieved. A patient-specific LBM equation was developed based on the relationship between LC fat volumes (FVLC) and whole-body fat mass (FMWB). This equation was cross-validated with an independent sample of 97 patients who also received whole-body PET/CT examinations. Its results were compared with the measurement of LBM from whole-body CT (reference standard) and the results of the James PE. Then, 241 patients with solid tumours who underwent PET/CT examinations before and after treatment were retrospectively retrieved. The treatment responses were evaluated according to the PE-based and LC-based PERCIST 1.0. Concordance between them was assessed using Cohen’s κ coefficient and Wilcoxon’s signed-ranks test. The impact of differing LBM algorithms on PERCIST 1.0 classification was evaluated. Results The FVLC were significantly correlated with the FMWB (r=0.977). Furthermore, the results of LBM measurement evaluated with LC images were much closer to the reference standard than those obtained by the James PE. The PE-based and LC-based PERCIST 1.0 classifications were discordant in 27 patients (11.2%; κ = 0.823, P=0.837). These discordant patients’ percentage changes of peak SUL (SULpeak) were all in the interval above or below 10% from the threshold (±30%), accounting for 43.5% (27/62) of total patients in this region. The degree of variability is related to changes in LBM before and after treatment. Conclusions LBM algorithm-dependent variability in PERCIST 1.0 classification is a notable issue. SUV normalised by LC-based LBM could change PERCIST 1.0 response classifications based on LBM estimated by the James PE, especially for patients with a percentage variation of SULpeak close to the threshold.

Influence of short-term dexfenfluramine therapy on glucose and lipid metabolism in obese non-diabetic patients

1993 ◽  
Vol 128 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Per H Andersen ◽  
Bjørn Richelsen ◽  
Jens Bak ◽  
Ole Schmitz ◽  
Niels S Sørensen ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Serum Insulin ◽  
Whole Body ◽  
Glucose Disposal ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Diabetic Patients ◽  
Obese Patients ◽  
Short Term ◽  
Glucose And Lipid Metabolism

In a short-term (eight days) double-blind crossover study involving 10 obese patients, the effects of dexfenfluramine on glucose and lipid metabolism were examined. The protocol comprised whole body in vivo measurements (hyperinsulinemic euglycemic clamp in combination with indirect calorimetry) and in vitro studies of isolated adipocytes (lipolysis and glucose transport). All study participants were weight stable during the study period (103.1±3.2, placebo vs 103.3±3.1 kg, dexfenfluramine, NS). The following parameters were significantly reduced after dexfenfluramine treatment: fasting levels of plasma glucose (6.2±0.2 vs 5.7±0.2 mmol/l, p<0.01), serum insulin (168.0±14.5 vs 138.9±7.9 pmol/l, p<0.05), serum C-peptide (0.68±0.03 vs 0.58±0.02 nmol/l, p<0.05) and total serum cholesterol (6.07±0.41 vs 5.48±0.38 mmol/l, p< 0.01). In the basal state glucose oxidation rate was significantly reduced by 36% (p<0.001), whereas non-oxidative glucose disposal was significantly increased by 41% (p<0.01), following dexfenfluramine treatment. Insulin-stimulated (2 mU·kg−1·min−1) glucose disposal rate tended to be increased (18%, p=0.10) after dexfenfluramine. In conclusion, dexfenfluramine possesses beneficial regulatory effects on glucose and lipid metabolism in non-diabetic obese patients, independently of weight loss.

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