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Acute lysine supplementation does not improve hepatic or peripheral insulin sensitivity in older, overweight individuals.

ABSTRACT: CONTEXT:Lysine supplementation may have a positive influence on the regulation of glucose metabolism but it has not been tested in the geriatric population. OBJECTIVE:We evaluated the impact of acute lysine supplementation using three randomized experimental scenarios: 1) oral glucose alone (control), 2) oral glucose and low-dose lysine (2 grams), and oral glucose and high dose lysine (5 grams) lysine in 7 older (66?±?1 years/age), overweight/obese (BMI?=?28?±?2 kg/m(2)) individuals. METHODS:We utilized a dual tracer technique (i.e., [6,6-(2)H2] glucose primed constant infusion and 1-[(13)C] glucose oral ingestion) during an oral glucose tolerance test (OGTT) to examine differences in hepatic and peripheral insulin sensitivity under all three scenarios. RESULTS:Post-absorptive plasma glucose and insulin concentrations were not different between the three trials. Similarly, the response of glucose and insulin concentrations during the oral glucose tolerance tests (OGTT) was similar in the three trials. The results of the Matsuda index (ISI/M) were also not different between the three trials. As an index of hepatic insulin sensitivity, there were no significant differences in the endogenous glucose rate of appearance (glucose Ra) for control, 2 g lysine and 5 g lysine (1.2?±?0.1, 1.1?±?0.1, 1.3?±?0.1 mg•kg(-1)•min(-1)), respectively. With respect to peripheral insulin sensitivity, there were no significant differences in the glucose rate of disappearance (glucose Rd) for control, 2 g lysine and 5 g lysine (4.2?±?0.1, 4.3?±?0.2, and 4.5?±?0.4 mg•kg(-1)•min(-1)), respectively. CONCLUSIONS:Previous studies in younger participants have suggested that lysine may have a beneficial effect on glucose metabolism. However, acute lysine supplementation in the older population does not facilitate beneficial changes in glucose Ra or glucose Rd.

SUBMITTER: Kim IY

PROVIDER: S-EPMC4198625 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Acute lysine supplementation does not improve hepatic or peripheral insulin sensitivity in older, overweight individuals.

Kim Il-Young IY Williams Rick H RH Schutzler Scott E SE Lasley Cosby J CJ Bodenner Donald L DL Wolfe Robert R RR Coker Robert H RH

Nutrition & metabolism 20141008 1

<h4>Context</h4>Lysine supplementation may have a positive influence on the regulation of glucose metabolism but it has not been tested in the geriatric population.<h4>Objective</h4>We evaluated the impact of acute lysine supplementation using three randomized experimental scenarios: 1) oral glucose alone (control), 2) oral glucose and low-dose lysine (2 grams), and oral glucose and high dose lysine (5 grams) lysine in 7 older (66 ± 1 years/age), overweight/obese (BMI = 28 ± 2 kg/m(2)) individua ...[more]

PMID: 25324894

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Project description:Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BRA) or devoid of (BRP) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O2) and reported as the slope of the relationship between O2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BRA (from -0.14 ± 0.04 to -0.05 ± 0.02 l·min-1·%[Formula: see text]-1, P = 0.01) versus BRP (from -0.10 ± 0.05 to -0.11 ± 0.05 l·min-1·%[Formula: see text]-1, P = 0.80), with no differences in heart rate responsiveness (BRA: from -0.47 ± 0.06 to -0.33 ± 0.04 beats·min-1·%[Formula: see text]-1, BRP: from -0.48 ± 0.07 to -0.42 ± 0.06 beats·min-1·%[Formula: see text]-1) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BRA and BRP (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BRA) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.

Project description:CONTEXT:Animal studies indicate that osteocalcin (OC), particularly the undercarboxylated isoform (unOC), affects insulin sensitivity and secretion, but definitive data from humans are lacking. OBJECTIVE:The objectives of the study were to determine whether total OC and unOC are independently associated with insulin sensitivity and ?-cell response in overweight/obese adults; whether glucose tolerance status affects these associations; and whether the associations are independent of bone formation, as reflected in procollagen type 1 amino propeptide (P1NP). DESIGN, SETTING, AND PARTICIPANTS:This was a cross-sectional study conducted at a university research center involving 63 overweight/obese adults with normal (n = 39) or impaired fasting glucose (IFG; n = 24). MAIN OUTCOME MEASURES:Serum concentrations of total/undercarboxylated OC and P1NP were assessed by RIA; insulin sensitivity was determined by iv glucose tolerance test (S(I)-IVGTT), liquid meal test (S(I) meal), and homeostasis model assessment of insulin resistance; ?-cell response to glucose [basal ?-cell response to glucose; dynamic ?-cell response to glucose; static ?-cell response to glucose; and total ?-cell response to glucose] was derived using C-peptide modeling of meal test data; and intraabdominal adipose tissue was measured using computed tomography scanning. RESULTS:Multiple linear regression, adjusting for intraabdominal adipose tissue and P1NP, revealed that total OC was positively associated with S(I)-iv glucose tolerance test (P < .01) in the total sample. OC was not associated with S(I) meal or homeostasis model assessment of insulin resistance. In participants with IFG, unOC was positively associated with static ?-cell response to glucose and total ?-cell response to glucose (P < .05), independent of insulin sensitivity. CONCLUSIONS:In overweight/obese individuals, total OC may be associated with skeletal muscle but not hepatic insulin sensitivity. unOC is uniquely associated with ?-cell function only in individuals with IFG. Further research is needed to probe the causal inference of these relationships and to determine whether indirect nutrient sensing pathways underlie these associations.

Project description:Aims/hypothesisInsulin resistance in skeletal muscle and liver plays a major role in the pathophysiology of type 2 diabetes. The hyperinsulinaemic-euglycaemic clamp is considered the gold standard for assessing peripheral and hepatic insulin sensitivity, yet it is a costly and labour-intensive procedure. Therefore, easy-to-measure, cost-effective approaches to determine insulin sensitivity are needed to enable organ-specific interventions. Recently, evidence emerged that plasma cathepsin D (CTSD) is associated with insulin sensitivity and hepatic inflammation. Here, we aimed to investigate whether plasma CTSD is associated with hepatic and/or peripheral insulin sensitivity in humans.MethodsAs part of two large clinical trials (one designed to investigate the effects of antibiotics, and the other to investigate polyphenol supplementation, on insulin sensitivity), 94 overweight and obese adults (BMI 25-35 kg/m2) previously underwent a two-step hyperinsulinaemic-euglycaemic clamp (using [6,6-2H2]glucose) to assess hepatic and peripheral insulin sensitivity (per cent suppression of endogenous glucose output during the low-insulin-infusion step, and the rate of glucose disappearance during high-insulin infusion [40 mU/(m2 × min)], respectively). In this secondary analysis, plasma CTSD levels, CTSD activity and plasma inflammatory cytokines were measured.ResultsPlasma CTSD levels were positively associated with the proinflammatory cytokines IL-8 and TNF-α (IL-8: standardised β = 0.495, p < 0.001; TNF-α: standardised β = 0.264, p = 0.012). Plasma CTSD activity was negatively associated with hepatic insulin sensitivity (standardised β = -0.206, p = 0.043), independent of age, sex, BMI and waist circumference, but it was not associated with peripheral insulin sensitivity. However, plasma IL-8 and TNF-α were not significantly correlated with hepatic insulin sensitivity.Conclusions/interpretationWe demonstrate that plasma CTSD activity, but not systemic inflammation, is inversely related to hepatic insulin sensitivity, suggesting that plasma CTSD activity may be used as a non-invasive marker for hepatic insulin sensitivity in humans.

Project description:BACKGROUND:Effects of resveratrol on metabolic health have been studied in several short-term human clinical trials, with conflicting results. Next to dose, the duration of the clinical trials may explain the lack of effect in some studies, but long-term studies are still limited. OBJECTIVES:The objective of this study was to investigate the effects of 6-mo resveratrol supplementation on metabolic health outcome parameters. METHODS:Forty-one overweight men and women (BMI: 27-35 kg/m2; aged 40-70 y) completed the study. In this parallel-group, double-blind clinical trial, participants were randomized to receive either 150 mg/d of resveratrol (n = 20) or placebo (n = 21) for 6 mo. The primary outcome of the study was insulin sensitivity, using the Matsuda index. Secondary outcome measures were intrahepatic lipid (IHL) content, body composition, resting energy metabolism, blood pressure, plasma markers, physical performance, quality of life, and quality of sleep. Postintervention differences between the resveratrol and placebo arms were evaluated by ANCOVA adjusting for corresponding preintervention variables. RESULTS:Preintervention, no differences were observed between the 2 treatment arms. Insulin sensitivity was not affected after 6 mo of resveratrol treatment (adjusted mean Matsuda index: 5.18 ± 0.35 in the resveratrol arm compared with 5.50 ± 0.34 in the placebo arm), although there was a significant difference in postintervention glycated hemoglobin (HbA1c) between the arms (P = 0.007). The adjusted means showed that postintervention HbA1c was lower on resveratrol (35.8 ± 0.43 mmol/mol) compared with placebo (37.6 ± 0.44 mmol/mol). No postintervention differences were found in IHL, body composition, blood pressure, energy metabolism, physical performance, or quality of life and sleep between treatment arms. CONCLUSIONS:After 6 mo of resveratrol supplementation, insulin sensitivity was unaffected in the resveratrol arm compared with the placebo arm. Nonetheless, HbA1c was lower in overweight men and women in the resveratrol arm. This trial was registered at Clinicaltrials.gov as NCT02565979.

Dataset Information

Acute lysine supplementation does not improve hepatic or peripheral insulin sensitivity in older, overweight individuals.

Publications

Acute lysine supplementation does not improve hepatic or peripheral insulin sensitivity in older, overweight individuals.

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