c-peptide and Hypoxia

Recent research in nutritional control of aging suggests that cytosolic increases in the reduced form of nicotinamide adenine dinucleotide and decreasing nicotinamide adenine dinucleotide metabolism plays a central role in controlling the longevity gene products sirtuin 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). High nutrition conditions, such as the diabetic milieu, increase the ratio of reduced to oxidized forms of cytosolic nicotinamide adenine dinucleotide through cascades including the polyol pathway. This redox change is associated with insulin resistance and the development of diabetic complications, and might be counteracted by insulin C-peptide. My research and others' suggest that the SIRT1-liver kinase B1-AMPK cascade creates positive feedback through nicotinamide adenine dinucleotide synthesis to help cells cope with metabolic stress. SIRT1 and AMPK can upregulate liver kinase B1 and FOXO3, key factors that help residential stem cells cope with oxidative stress. FOXO3 directly changes epigenetics around transcription start sites, maintaining the health of stem cells. 'Diabetic memory' is likely a result of epigenetic changes caused by high nutritional conditions, which disturb the quiescent state of residential stem cells and impair tissue repair. This could be prevented by restoring SIRT1-AMPK positive feedback through activating FOXO3.

Topics: Aging; AMP-Activated Protein Kinases; Animals; C-Peptide; Diabetes Complications; Diabetic Angiopathies; Disease Models, Animal; Epigenesis, Genetic; Feedback, Physiological; Forkhead Box Protein O3; Humans; Hypoxia; Insulin Resistance; NAD; Oxidation-Reduction; Oxidative Stress; Signal Transduction; Sirtuin 1

PlanHab is a planetary habitat simulation study. The atmosphere within future space habitats is anticipated to have reduced Po2, but information is scarce as to how physiological systems may respond to combined exposure to moderate hypoxia and reduced gravity. This study investigated, using a randomized-crossover design, how insulin sensitivity, glucose tolerance, and circulating lipids were affected by 16 days of horizontal bed rest in normobaric normoxia [NBR: FiO2 = 0.209; PiO2 = 133.1 (0.3) mmHg], horizontal bed rest in normobaric hypoxia [HBR: FiO2 = 0.141 (0.004); PiO2 = 90.0 (0.4) mmHg], and confinement in normobaric hypoxia combined with daily moderate intensity exercise (HAMB). A mixed-meal tolerance test, with arterialized-venous blood sampling, was performed in 11 healthy, nonobese men (25-45 yr) before (V1) and on the morning ofday 17of each intervention (V2). Postprandial glucose and c-peptide response were increased at V2 of both bed rest interventions (P< 0.05 in each case), with c-peptide:insulin ratio higher at V2 in HAMB and HBR, both in the fed and fasted state (P< 0.005 in each case). Fasting total cholesterol was reduced at V2 in HAMB [-0.47 (0.36) mmol/l;P< 0.005] and HBR [-0.55 (0.41) mmol/l;P< 0.005]. Fasting HDL was lower at V2 in all interventions, with the reduction observed in HBR [-0.30 (0.21) mmol/l] greater than that measured in HAMB [-0.13 (0.14) mmol/l;P< 0.005] and NBR [-0.17 (0.15) mmol/l;P< 0.05]. Hypoxia did not alter the adverse effects of bed rest on insulin sensitivity and glucose tolerance but appeared to increase insulin clearance. The negative effect of bed rest on HDL was compounded in hypoxia, which may have implications for long-term health of those living in future space habitats.

Topics: Adult; Bed Rest; C-Peptide; Cholesterol; Cross-Over Studies; Fasting; Glucose; Glucose Tolerance Test; Humans; Hypogravity; Hypoxia; Insulin; Insulin Resistance; Lipids; Male

To examine the effects of acute altitude-induced hypoxia on the hormonal and metabolic response to ingested glucose, 8 young, healthy subjects (5 men and 3 women; age, 26 +/- 2 years; body mass index, 23.1 +/- 1.0 kg/m(2)) performed 2 randomized trials in a hypobaric chamber where a 75-g glucose solution was ingested under simulated altitude (ALT, 4300 m) or ambient (AMB, 362 m) conditions. Plasma glucose, insulin, C-peptide, epinephrine, leptin, and lactate concentrations were measured at baseline and 30, 60, 90, and 120 minutes after glucose ingestion during both trials. Compared with AMB, the plasma glucose response to glucose ingestion was reduced during the ALT trial (P = .04). There were no differences in the insulin and C-peptide responses between trials or in insulin sensitivity based on the homeostasis model assessment of insulin resistance. Epinephrine and lactate were both elevated during the ALT trial (P < .05), whereas the plasma leptin response was reduced compared with AMB (P < .05). The data suggest that the plasma glucose response is suppressed at ALT, but this is not due to insulin per se because insulin and C-peptide levels were similar for both trials. Elevated plasma epinephrine and lactate during ALT are indicative of increased glycogenolysis, which may have masked the magnitude of the reduced glucose response. We conclude that, during acute altitude exposure, there is a rapid metabolic response that is accompanied by a shift in the hormonal milieu that appears to favor increased glucose utilization.

Topics: Adult; Altitude; Blood Glucose; C-Peptide; Epinephrine; Female; Glucose; Humans; Hypoxia; Insulin; Insulin Resistance; Lactic Acid; Leptin; Male; Solutions

Hypoxia was shown to reduce insulin concentrations at rest and during exercise. However, some studies have also demonstrated increases in the hormone associated with arterial desaturation. This study was conducted in order to decide [1] whether acute alveolar hypoxia increased or decreased the circulating insulin levels, and [2] to elucidate whether interactions of insulin with other hormones were of relevance in this respect. Glucose (GLU), insulin (INS), c-peptide (CP), adrenaline and noradrenaline (CATs), atrial natriuretic peptide (ANP) and cortisol (CORT) as well as the capillary blood gases were determined in 15 healthy fasting male volunteers (age: 26.2 +/- 2.8 years, body mass index: 22.4 +/- 2.7 kg.m-2). On two separate test days the subjects breathed, in random order, either normal air (N) or a gas mixture with reduced oxygen content (H; FIO2: 0.14). Measurements were made at rest as well as during an incremental cycle exercise in a supine position (increments of 6 min and 50 W) at 100 W and 150 W, at volitional exhaustion (N: 227 +/- 36 W; H: 200 +/- 32 W) as well as in the 5th min of recovery. Arterial desaturation was seen throughout on H-day. At rest all hormones and GLU were normal and showed no influence of H. During exercise INS remained constant on N-day, increased on H-day and was significantly higher with H than with N, most pronounced at 150 W and at volitional exhaustion with 20%, respectively. For CP and GLU no significant exercise-induced changes were seen on either test day and no influence of H was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; C-Peptide; Exercise; Humans; Hypoxia; Insulin; Male

Topics: Acclimatization; Adaptation, Physiological; Animals; Asthma; Biological Evolution; Blood Vessels; C-Peptide; Calcium; Diabetic Angiopathies; Ecosystem; Hibernation; Humans; Hypoxia; Kidney Tubules; Lung; Receptors, Calcium-Sensing; Respiration

High-fructose intake induces metabolic syndrome and cardiac dysfunction. Chronic intermittent hypobaric hypoxia (CIHH) preserves cardiac function during ischemia. We hypothesized that CIHH restores the impaired cardiac function in fructose-fed rats. Sprague-Dawley rats were randomly subject to treatment with fructose (10% fructose in drinking water for 6 weeks), CIHH (simulated 5000 m altitude, 6 h/day for 6 weeks in a hypobaric chamber), and CIHH plus fructose groups. In addition to an increase in blood pressure, fructose feeding caused elevated serum levels of glucose, fasting insulin and insulin C peptide, triglyceride, cholesterol, and mass ratio of heart to body. CIHH treatment decreased the arterial blood pressure, serum levels of biochemical markers, and cardiac hypertrophy in fructose-fed rats. Furthermore, CIHH treatment improved the recovery of left ventricular function after ischemia-reperfusion procedure (30 min global no-flow ischemia followed by 60 min of reperfusion) in rats with or without fructose feeding. In addition, CIHH treatment caused a significant increase in superoxide dismutase (SOD) activity and decrease in malondialdehyde level in cardiac myocardium experiencing ischemia-reperfusion in control and fructose-fed rats. Collectively, these data suggest that CIHH improve impaired cardiac function in fructose-fed rats through enhancing antioxidation in the myocardium.

Topics: Animal Feed; Animals; Antioxidants; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Fructose; Heart; Hypoxia; Insulin; Male; Malondialdehyde; Myocardium; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Superoxide Dismutase; Triglycerides; Ventricular Function, Left

One of the biggest challenges of premature birth is acute hypoxia. Hypothermia during acute hypoxic periods may be beneficial. We hypothesized that prevention of hypothermia during neonatal hypoxia disrupts glucose homeostasis and places additional metabolic challenges on the neonate. Pups at PD2 and PD8 were exposed to 8% O2 for 3 h, during which they were allowed to either spontaneously cool or were kept isothermic. There was also a time control group that was subjected to normoxia and kept isothermic. Plasma glucose, insulin, C-peptide, corticosterone, and catecholamines were measured from samples collected at baseline, 1 h, 2 h, and 3 h. In postnatal day 2 (PD2) rats, hypoxia alone resulted in no change in plasma glucose by 1 h, an increase by 2 h, and a subsequent decrease below baseline values by 3 h. Hypoxia with isothermia in PD2 rats elicited a large increase in plasma insulin at 1 h. In PD8 rats, hypoxia with isothermia resulted in an initial increase in plasma glucose, but by 3 h, glucose had decreased significantly to below baseline levels. Hypoxia with and without isothermia elicited an increase in plasma corticosterone at both ages and an increase in plasma epinephrine in PD8 rats. We conclude that the insulin response to hypoxia in PD8 rats is associated with an increase in glucose similar to an adult; however, insulin responses to hypoxia in PD2 rats were driven by something other than glucose. Prevention of hypothermia during hypoxia further disrupts glucose homeostasis and increases metabolic challenges.

Topics: Animals; Animals, Newborn; Blood Glucose; Body Temperature; Body Temperature Regulation; C-Peptide; Catecholamines; Corticosterone; Female; Homeostasis; Hypothermia; Hypoxia; Insulin; Models, Animal; Pregnancy; Rats; Rats, Sprague-Dawley

To clarify which endocrine modifications can be observed in acute hypoxaemic respiratory failure, 15 severely ill male patients [PAT; median age: 61 (range: 48 years); median height: 173 (range: 12) cm; median mass: 73 (range 31) kg] were investigated immediately upon admission to an intensive care unit (ICU) for this clinical disorder. Before starting treatment, the blood gases were measured and a number of selected hormones with special relevance for an ICU setting were determined. These are known to be modified by acute hypoxaemia in healthy subjects and to possess glucoregulatory properties, or an influence upon cardiocirculation or the vascular volume regulation: insulin, cortisol, adrenaline, noradrenaline, atrial natriuretic peptide, renin, aldosterone, angiotensin converting enzyme, and endothelin-I (ET). To elucidate whether potential endocrine changes resulted from acute hypoxaemia alone, the underlying disease, or unspecific influences connected with the ICU setting, all measurements were compared to those of a completely healthy reference group (REF) with comparable acute experimental hypoxaemia. The latter state was achieved by having the REF breathe a gas mixture with the oxygen content reduced to 14% (H). In the REF, neither the medians nor the distribution of endocrinologic measurements were modified significantly by acute hypoxaemia. In the PAT, the medians were increased considerably, yet with a slight diminution of ET. The distribution of individual values was considerably broader than in the REF with H. In conclusion, considerable increases in the means of the above hormones, with the exception of ET, can be registered in severely ill patients admitted to ICUs with acute hypoxaemic failure. However, such modifications cannot be considered attributable exclusively to acute arterial hypoxaemia. The underlying clinical disorders, such as septicaemia or an unspecific endocrine epiphenomenon, including severe and not only hypoxaemic stress, seem to be predominant.

Topics: Acute Disease; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; C-Peptide; Critical Care; Endocrine Glands; Endothelins; Epinephrine; Humans; Hydrocortisone; Hypoxia; Insulin; Male; Middle Aged; Norepinephrine; Peptidyl-Dipeptidase A; Pneumonia; Renin; Respiratory Insufficiency

Nocturnal secretion of growth hormone is impaired in patients with obstructive sleep apnea (OSA), but the metabolic consequences have not been reported. We measured blood levels of the hormones insulin, C-peptide, growth hormone, cortisol and glucagon together with the intermediary metabolites of carbohydrate (glucose, pyruvate, lactate, alanine) and lipid metabolism [glycerol, nonesterified fatty acids (NEFA), 3-hydroxybutyrate] in six obese nondiabetic men with OSA on two nights. In the first study, the untreated subjects showed frequent apneas and consequent hypoxemia. The hormone and metabolite concentrations were compared with those obtained on the following night when the subjects were treated effectively with nasal continuous positive airway pressure (CPAP). There were no significant differences in the concentrations of insulin, C-peptide, cortisol or glucagon. We confirmed a marked reduction in growth hormone concentrations in OSA, with a significant increase on the CPAP night. The nocturnal profiles of glucose, pyruvate, lactate, alanine and glycerol showed no differences between the two nights, but concentrations of NEFA and 3-hydroxybutyrate, both products of lipolysis, were significantly greater on the treatment night. Because growth hormone has a lipolytic action, the results suggest that suppression of secretion of growth hormone in untreated OSA results in impaired lipolysis, which is rapidly reversed by nasal CPAP.

Topics: Adult; Aged; C-Peptide; Carbohydrate Metabolism; Circadian Rhythm; Glucagon; Growth Hormone; Humans; Hydrocortisone; Hypoxia; Insulin; Lipid Metabolism; Male; Middle Aged; Polysomnography; Positive-Pressure Respiration; Sleep Apnea Syndromes

Radioimmunoassays of plasma C-peptide, and plasma and erythrocyte insulin were made in mixed venous-arterial blood specimens of normal children and those with congenital heart diseases. In all cases, insulin level was higher in erythrocytes, as compared to plasma specimens, obviously due to active insulin deposition by erythrocytes. Venous-arterial difference in insulin may be indicative of tissue insulin uptake. Respiratory and circulatory hypoxia is associated with decreased erythrocyte capacity for insulin deposition and tissue insulin uptake. It is suggested that plasma C-peptide content may be an indicator of pancreatic function.

Topics: Biological Transport; C-Peptide; Child; Child, Preschool; Erythrocytes; Heart Defects, Congenital; Humans; Hydrocortisone; Hypoxia; Insulin; Insulin Secretion; Pancreas; Tissue Distribution

Increased cord blood C-peptide levels in neonates born to mothers with gestational diabetes (GD) were directly correlated with the increased relative birth weight ratio (BWR) of these neonates. In addition, the percentage oxygen saturation of the cord blood was inversely correlated with cord blood C-peptide levels and with the relative BWR. These correlations were absent in neonates delivered to normal mothers. The results indicate the presence of both hyperinsulinaemia and mild hypoxaemia in neonates of mothers with GD. In poorly controlled diabetic pregnancy this hypoxaemia may constitute an important fetal risk factor.

Topics: Birth Weight; C-Peptide; Female; Fetal Blood; Humans; Hyperinsulinism; Hypoxia; Infant, Newborn; Oxygen; Partial Pressure; Pregnancy; Pregnancy in Diabetics