Biomedical subjects

G Boden

Publications and source records attributed to G Boden.

At least 55 records · Page 3Linked to original sources

PubMed1996

Increased human immunodeficiency virus type 1 replication in human peripheral blood mononuclear cells induced by ethanol: potential immunopathogenic mechanisms.

Previous studies have shown that alcohol ingestion significantly increases human immunodeficiency virus type 1 (HIV-1) replication in peripheral blood mononuclear cells (PBMC) isolated and infected with HIV-1 in vitro. Whether the increased replication of HIV-1 observed after alcohol ingestion was due to unknown factors released from the gastrointestinal tract during alcohol ingestion or to certain metabolites produced by intestinal flora that degraded alcohol was investigated. In addition, cellular mechanisms involved in the increased replication of HIV-1 after alcohol exposure were evaluated. Twelve healthy HIV-1-seronegative subjects abstained from alcoholic beverages for >10 days. Nine were infused with 500 mg/kg ethanol (7.5% at 20 ml/kg/h) in saline, whereas 3 were infused with saline alone. Compared with saline-infused subjects, ethanol-infused subjects' PBMC exhibited significantly increased replication of HIV-1 when infected in vitro, which was associated with increased inhibition of CD8+ T lymphocytes' function by alcohol.

Adolescent↗

PubMed1996

Effects of prolonged glucose infusion on insulin secretion, clearance, and action in normal subjects.

It was the aim of this study to determine whether prolonged hyperglycemia can produce "glucose toxicity" in normal human subjects. To this end, plasma glucose was clamped at approximately 5, approximately 8.8, and approximately 12.6 mM for 68 h in healthy volunteers. Rates of insulin secretion (by deconvolution of plasma C-peptide) and rates of insulin clearance [area under curve (AUC) 24 h insulin secretion/AUC 24 h insulin] were determined. Pre- and posthyperglycemia glucose turnover was measured (with [6,6-2H2]glucose) during euglycemic-hyperinsulinemic clamping to assess peripheral (muscle) and hepatic insulin action. Hyperglycemia (approximately 12.6 mM) for 68 h was associated with significant reductions in rates of insulin secretion (-35%, P < 0.05), insulin clearance (-57%, P < 0.05), glucose infusion rates needed to maintain hyperglycemia (-36%, P < 0.05), and insulin-stimulated glucose uptake (-55%, P < 0.01). No significant changes were seen during approximately 8.8 mM hyperglycemia or during euglycemia. These data showed that 12.6 mM hyperglycemia, but not 8.8 mM hyperglycemia or euglycemia, was associated with reduced insulin secretion, insulin clearance, and peripheral (muscle) insulin action. We concluded that 1) in normal subjects, desensitization to glucose involving beta-cells and muscle developed at plasma glucose concentrations between approximately 9 and approximately 12 mM, and 2) these effects were partially compensated for by a decrease in insulin clearance.

Adult↗

PubMed1996

Evidence for a circadian rhythm of insulin secretion.

Insulin secretion was studied in healthy volunteers at three different levels of glycemia. Plasma glucose was clamped at approximately 5, approximately 8.8 and approximately 12.6 mM for 68 h. Measured were serum insulin concentration and insulin secretion rates (ISR), the latter by deconvolution of plasma C-peptide concentration. Rhythmic patterns of ISR were identified (with a refined first-order Fourier transform) at all three glucose concentrations tested but were most clearly seen at 12.6 mM. ISR and serum insulin concentration changed in a circadian (approximately 24 h) rhythm, increasing from a nadir between midnight and 6 A.M. and reaching a peak between noon and 6 P.M. At 12.6 mM hyperglycemia, the amplitude of the insulin concentration cycles was greater than that of the ISR cycles (+/- 13.0 vs. +/- 8.7%) due to a decrease in insulin clearance (from 1.55 to 0.5 l/min, P < 0.01). Plasma melatonin levels (a marker of light-dark rhythmicity) changed in the opposite direction, i.e., they peaked when ISR bottomed and bottomed when ISR peaked. We concluded that normal human subjects have a circadian rhythm of insulin secretion, which becomes more apparent with rising ISR, and that circadian changes in ISR, rising during the day and falling during the night, may be one explanation for the well-established observation that glucose tolerance and insulin responses to glucose and meals are higher in the morning than at night.

Adult↗

PubMed1996

Kininogen changes in human plasma following a test meal or insulin administration.

The effect of food intake and of insulin on plasma bradykinin (BK) reserves [total (TK), high-molecular-weight (HK), and low-molecular-weight kininogen (LK)] was followed by determining (by enzyme-linked immunosorbent assay) the amount of BK released by trypsin from plasma collected before and after a test meal or hyperinsulinemic clamping. LK was kininogen remaining in plasma after in vitro kaolin treatment, which removes all HK. HK was the difference between TK and LK. Thirty minutes after a test meal, TK and HK decreased by 8.0 +/- 0.6 and 39.7 +/- 6.6%, respectively, in six of seven subjects. Return to prealimentary levels occurred after 90-120 min. Hyperinsulinemia, comparable to that arising after the test meal, partly reproduced such treatment's effect on TK and HK but did not affect blood or plasma kininogen in vitro. Observed postprandial hypotension and increased leg blood flow could be caused, in part, by BK released from plasma HK after cleavage at vascular, possibly endothelial, sites activated by insulin.

Adult↗

PubMed1996

Effect of fasting on serum leptin in normal human subjects.

We have studied the effect of fasting on serum leptin levels in normal volunteers. Five normal-weight (BMI < 28, 2 males/3 females) and five obese subjects (BMI > 28, 2 males/3 females) were fasted (0 Kcal) for 52 h. Mean plasma glucose decreased from 88 +/- 3 to 63 +/- 5 mg/dl, serum insulin from 16 +/- 1 to 10 +/- 1 microU/ml, plasma beta-hydroxybutyrate increased from 0.2 +/- 0.1 to 1.8 +/- 0.4 mumol/ml. Serum leptin levels were higher in the obese than in the normal-weight volunteers (31 +/- 12 vs 11 +/- 3 ng/ml, p < 0.01). In the obese, serum leptin decreased from 31 +/- 10 to 12 +/- 5 ng/ml aft552 h (-72%, p < 0.001); in the normal-weight it decreased from 11 +/- 3 to 4 +/- 0.5 ng/ml (-64%, p < 0.001). Serum leptin correlated positively with serum insulin (r = 0.51, p < 0.001) and with plasma glucose (r = 0.61, p < 0.001). To determine effects of fasting induced decreases in plasma glucose and insulin on serum leptin, four normal subjects (3 males/1 female) were fasted for 72 h while their plasma glucose was clamped at basal levels with a variable rate glucose infusion. In these volunteers, serum leptin and insulin concentrations remained unchanged. In summary, the rapid decrease in serum leptin levels during fasting indicated that leptin release was regulated by factors other than changes in body fat mass. The lack of leptin changes during fasting, when basal insulin and glucose levels were maintained at basal levels, suggested that insulin and/or glucose may play a role in the regulation of leptin release.

3-Hydroxybutyric Acid↗

PubMed1996

Acute and chronic effects of insulin on leptin production in humans: Studies in vivo and in vitro.

This study was undertaken to investigate the changes in obesity (OB) gene expression and production of leptin in response to insulin in vitro and in vivo under euglycemic and hyperglycemic conditions in humans. Three protocols were used: 1) euglycemic clamp with insulin infusion rates at 40, 120, 300, and 1,200 mU / m / min carried out for up to 5 h performed in 16 normal lean individuals, 30 obese individuals, and 31 patients with NIDDM; 2) 64-to 72-h hyperglycemic (glucose 12.6 mmol/l) clamp performed on 5 lean individuals; 3) long-term (96-h) primary culture of isolated abdominal adipocytes in the presence and absence of 100 nmol/l insulin. Short-term hyperinsulinemia in the range of 80 to > 10,000 microU/ml had no effect on circulating levels of leptin. During the prolonged hyperglycemic clamp, a rise in leptin was observed during the last 24 h of the study (P < 0.001). In the presence of insulin in vitro, OB gene expression increased at 72 h (P < 0.01), followed by an increase in leptin released to the medium (P < 0.001). In summary, insulin does not stimulate leptin production acutely; however, a long-term effect of insulin on leptin production could be demonstrated both in vivo and in vitro. These data suggest that insulin regulates OB gene expression and leptin production indirectly, probably through its trophic effect on adipocytes.

Adipocytes↗

PubMed1996

Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production.

Diurnal variation in insulin sensitivity in patients with NIDDM has long been suspected but has been difficult to document mainly because of the interdependence of changes in glucose and insulin. Stable serum insulin levels during hyperglycemic clamping in patients with NIDDM in the present study provided the opportunity to examine changes in insulin sensitivity unaffected by changes in blood glucose and insulin concentrations. Six patients with NIDDM (four men and two women, BMI 33.9 +/- 2.5) underwent hyperglycemic (11.1 mmol/l, approximately 200 mg/dl) clamping for 72 h. Measured were serum insulin, free fatty acid (FFA), cortisol, and growth hormone concentrations and rates of insulin secretion, insulin clearance, and glucose infusion rate (GIR) needed to maintain hyperglycemia. In addition, five patients (three men and two women, BMI 32.6 +/- 0.6) underwent hyperglycemic clamping for 24 h with hourly determinations of hepatic glucose production (HGP) and glucose disappearance rates (GRd). GIR, reflecting insulin sensitivity, changed rhythmically with a cycle duration of 22.9 +/- 1.4 h and an amplitude of 47.8 +/- 11.2%. GIR was lowest at 8:31 a.m. (+/- 52 min) and highest at 7:04 p.m. (+/- 58 min). Circadian changes in GIR were completely accounted for by changes in HGP, while GRd remained unchanged. Plasma levels of FFAs and cortisol also exhibited circadian fluctuations, and their blood levels correlated negatively with GIR (r = -0.72 and -0.64, respectively). We concluded that insulin sensitivity in patients with NIDDM changed with circadian (approximately 24 h) rhythmicity (decreasing during the night and increasing during the day). These changes were unrelated to blood levels of glucose and insulin, insulin clearance, exercise, food intake, and sleep. They were caused by circadian changes in HGP, which in turn were closely correlated with circadian changes in blood FFA and cortisol levels. We believe that recognition of these circadian changes has implications for the diagnosis and the treatment of patients with NIDDM.

Alanine↗

PubMed1996

Fatty acids and insulin resistance.

We have demonstrated that physiological elevations in plasma free fatty acid concentrations inhibit insulin-stimulated glucose uptake in a dose-dependent manner in normal control subjects and in patients with NIDDM. Two possible mechanisms were identified: 1) a fat-related inhibition of glucose transport or phosphorylation that appeared after 3-4 h of fat infusion and 2) a decrease in muscle glycogen synthase activity that appeared after 4-6 h of fat infusion. We conclude that elevations of plasma FFAs caused insulin resistance and hence may play a significant role in the pathogenesis of insulin resistance in obesity and NIDDM.

Animals↗

PubMed1995

Metabolic effects of darglitazone, an insulin sensitizer, in NIDDM subjects.

Insulin resistance is a significant pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM). A new class of drugs, the thiazolidinediones, have been shown to lower blood glucose levels without stimulating insulin secretion. We report the metabolic effect of the thiazolidinedione, darglitazone, in obese NIDDM subjects. Nineteen subjects were enrolled in a double-blind placebo-controlled study in which 25 mg of darglitazone was given once a day for 14 days. Nine subjects received the active drug and ten subjects received placebo. Darglitazone-treated subjects showed; 1) a decrease in 24-h plasma glucose area under the curve from 292.8 +/- 31.2 to 235.2 +/- 21.6 mmol.h-1.l-1 p = 0.002; 2) a decrease in 24-h serum insulin area under the curve from 1027.2 +/- 254.4 to 765.6 +/- 170.4 microU.h-1.l-1 p = 0.045; 3) a decrease in 24-h non-esterified fatty acid area under the curve from 1900 +/- 236 to 947 +/- 63 g.h-1.l-1 p = 0.002; 4) a decrease in mean 24-h serum triglyceride by 25.9 +/- 6.2% as compared to -3.9 +/- 4.8% for the placebo-treated group, p = 0.012. Placebo-treated subjects showed no change in their metabolic parameters after treatment. Thus, darglitazone is effective in increasing insulin effectiveness in obese NIDDM subjects. The potential for this and similar drugs to treat or prevent NIDDM as well as the insulin-resistance syndrome needs to be explored.

Blood Glucose↗

PubMed1995

Release, oxidation, and reesterification of fatty acids from infused triglycerides: effect of heparin.

We have investigated the effects of heparin on rates of fatty acid (FA) release, oxidation, and reesterification from intravenously (IV) infused triglycerides (TGs) during euglycemic (4.7 mmol.L-1) hyperinsulinemia (approximately 450 pmol.L-1). Four healthy men (aged 31 +/- 3 years; body mass index, 26.1 +/- 0.9 kg/m2) received i.v. TGs (1.02 mmol TG.kg-1.4 h-1), four other men (aged 24.3 +/- 2.8 years: body mass index, 24.7 +/- 1.7 kg/m2) received TGs plus heparin (200-U bolus followed by 0.4 U.kg-1.min-1), and nine men and one woman (aged 28.8 +/- 2.3 years; body mass index, 23.1 +/- 0.9 kg/m2) received saline (controls). Heparin increased lipolysis from infused TGs (to 1.0 +/- 0.1 from 0.3 +/- 0.1 mmol.kg-1.4 h-1, P < .01), increased plasma free fatty acids ([FFA] to 737 +/- 32 from 597 +/- 136 mumol.L-1, P < .05). and increased FA reesterification (to 0.84 +/- 0>14 from 0.18 +/- 0.12 mmol.kg-1.4 h-1, P < .02), but had no effect o n FA oxidation (0.13 +/- 0.02 v 0.12 +/- 0.04 mmol.kg-4 h-1) or net energy gain (167 +/- 42 v 243 +/- 79 kJ.4 h-1). In summary, addition of heparin (1) increased lipolysis (to approximately 98% from approximately 29%) and reesterification (to approximately 82% from approximately 17%) of infused TG, but had no significant effects on fat oxidation (approximately 12%) and net energy gain. We conclude that heparin accelerated removal of infused lipid from the blood and its deposition into endogenous fat depots. Since the doses of heparin and insulin used in this study were higher than those generally used in total parenteral nutrition protocols, our results may not be strictly applicable to the usual clinical situation.

Adult↗

PubMed1995

Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.

It was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (approximately 11mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat/heparin and two types of euglycemic (approximately 5mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin. During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation). Fat/heparin infusion did not affect basal glucose uptake, but inhibited total stimulated (insulin stimulated plus basal) glucose uptake by 40-50% in isoglycemic and in euglycemic patients at plasma FFA concentration of approximately 950 and approximately 550 microM, respectively. In isoglycemic patients, the 40-50% inhibition of total stimulated glucose uptake was due to near complete inhibition of the insulin-stimulated part of glucose uptake. Proportional inhibition of glucose uptake, glycogen synthesis, and glycolysis suggested a major FFA-mediated defect involving glucose transport and/or phosphorylation. In summary, fat produced proportional inhibitions of insulin-stimulated glucose uptake and of intracellular glucose utilization. We conclude, that physiologically elevated levels of FFa could potentially be responsible for a large part of the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus.

Aged↗

PubMed1995

Effects of a 48-h fat infusion on insulin secretion and glucose utilization.

To determine the effects of prolonged elevation of plasma free fatty acids (FFAs) on insulin secretion, we infused Liposyn II (4.3 mumol.kg-1.min-1) plus heparin (0.4 U.kg-1.min-1) intravenously into six healthy volunteers for 48 h. Another six volunteers received saline infusions and served as control subjects. In all 12 subjects (11 men and 1 woman), plasma glucose was clamped at approximately 8.6 mmol/l. Liposyn/heparin infusion resulted in a 9.4-fold increase in plasma FFA concentration (from 132 to 1,237 mumol/l), a 46% increase in insulin secretion rates (from 241 to 352 pmol/min, P < 0.05) (determined by deconvolution of plasma C-peptide concentration), and a 30% decrease, during the initial 24 h, in the rate of glucose infusion needed to maintain hyperglycemia (from 55.5 to 39.1 mumol.kg-1.min-1, P < 0.02). This decrease disappeared during the second 24 h. In summary, we found that physiologically elevated plasma FFAs 1) potentiated glucose-stimulated insulin secretion for 48 h and 2) initially caused peripheral insulin resistance that disappeared during the 2nd day, probably as a result of elevated circulating insulin levels. We conclude that in healthy volunteers under hyperglycemic conditions, fat infusion produced insulin resistance that was compensated for after approximately 24 h by persistent hypersecretion of insulin.

Adult↗

PubMed1994

Glucose transporter proteins in human insulinoma.

OBJECTIVE: To determine the reason patients with insulinoma are unable to cease insulin secretion during hypoglycemia. PATIENTS: Five patients with insulinoma. DESIGN: All patients fasted for up to 25 hours, during which blood was obtained serially for determination of glucose and insulin concentrations. Insulinomas were surgically removed from all patients and Glut 1 and Glut 2 transporter proteins were measured in solubilized tumor membranes by immune blotting. RESULTS: In all patients, serum insulin concentrations failed to decrease to less than 30.0 pmol/L (< 5.0 microU/mL) and C-peptide concentrations to less than 0.08 nmol/L during hypoglycemia (glucose concentration, < 2.2 mmol/L) that was induced by fasting. The islet cell tumors from all five patients contained Glut 1, a low-Km glucose transporter protein, which is not normally present in beta-cells. Glut 2, a high-Km glucose transporter protein, which is normally prevalent in beta-cells, was undetectable in one patient and was present in what appeared to be low concentrations in the remaining four patients. CONCLUSIONS: Our data are compatible with the concept that continued glucose transport, mediated by the low-Km Glut 1 glucose transporter, was responsible for continued insulin release during hypoglycemia in these patients.

Adult↗

PubMed1994

Epinephrine secretion, hypoglycemia unawareness, and diabetic autonomic neuropathy.

The failure of some type I diabetic patients to secrete epinephrine and glucagon in response to hypoglycemia has been documented by many investigators, and most studies have confirmed that an inability to secrete these counterregulatory hormones places patients at risk for developing clinical hypoglycemia. Inadequate acute glucose counterregulation can result from multiple mechanisms. Failure of central glucoreceptors to recognize hypoglycemia and to activate counterregulation may be the most common. Decreased central recognition of hypoglycemia results from either strict antecedent glucose control or from a recent hypoglycemic event. Controversy about the relation between autonomic neuropathy and counterregulatory hormone secretion has arisen because divergent criteria have been used in the published studies for the diagnosis of autonomic neuropathy. Advanced adrenergic neuropathy, as evidenced by orthostatic hypotension, generally leads to decreased epinephrine secretion after hypoglycemia. Subclinical neuropathy, however, as diagnosed from measurement of heart rate variability, may diminish the awareness of hypoglycemia but does not affect counterregulatory hormone secretion. Failure of counterregulatory hormone secretion in some patients with type I diabetes, however, may represent a selective autonomic neuropathy; the disease has limited the patient's ability to secrete epinephrine and pancreatic polypeptide in response to hypoglycemia even though it has spared the autonomic neurons responsible for cardiovascular reflexes. Finally, recent provocative reports indicate that decreased responsiveness to adrenergic stimuli may cause hypoglycemia unawareness in some patients. Further documentation of this mechanism is required, and its relative importance with respect to other mechanisms needs to be established. These questions are increasingly important clinically because the Diabetes Control and Complications Trial has confirmed that the prevalence of severe hypoglycemia remains a major obstacle to attempts to prevent diabetic complications with intensive insulin therapy. Until glucose counterregulation is more fully understood and methods for preventing hypoglycemia developed, patients with recurrent hypoglycemia unawareness or a history of hypoglycemia-related accidents should probably not be treated with intensive insulin therapy.

Autonomic Nervous System Diseases↗

PubMed1994

Glucose metabolism in the infant weighing less than 1100 grams.

We studied the rate of endogenous glucose production and disappearance in a group of 10 clinically stable < 1100 gm infants in the first week of life, using stable-isotope (6,6-2H-glucose) dilution analysis for a 2-hour study period. Plasma glucose and insulin concentrations at 2 hours were 5.4 +/- 2.5 mmol/L (97 +/- 15 mg/dl) and 71.4 +/- 2.9 pmol/L, respectively, and did not change during the study period. The rate of glucose disappearance was 37 +/- 10 mumol/kg (6.77 +/- 0.55 mg/kg) per minute. The rate of endogenous glucose production was 12.3 +/- 11 mumol/kg (2.22 +/- 0.61 mg/kg) per minute. The exogenous glucose infusion rate was 25.2 +/- 8.4 mumol/kg (4.54 +/- 0.47 mg/kg) per minute. Endogenous glucose production was correlated with plasma glucose concentration (r = 0.76; p < 0.05) and the rate of glucose disappearance (r = 0.75; p < 0.05); plasma glucose concentration was correlated with the rate of disappearance (r = 0.87; p = < 0.01) and insulin concentrations (p < 0.05). We conclude that infants who weight < 1100 gm utilize three to four times more glucose per kilogram of body weight than adults, reflecting their higher ratio of brain to body weight. Endogenous glucose production provided only approximately one third of the glucose needed--a mandate for the exogenous infusion of glucose to prevent the development of hypoglycemia.

Blood Glucose↗

PubMed1994

Mechanisms of fatty acid-induced inhibition of glucose uptake.

Increased plasma FFA reduce insulin-stimulated glucose uptake. The mechanisms responsible for this inhibition, however, remain uncertain. It was the aim of this study to determine whether the FFA effect was dose dependent and to investigate its mechanism. We have examined in healthy volunteers (13 male/1 female) the effects of three steady state plasma FFA levels (approximately 50, approximately 550, approximately 750 microM) on rates of glucose uptake, glycolysis (both with 3-3H-glucose), glycogen synthesis (determined with two independent methods), carbohydrate (CHO) oxidation (by indirect calorimetry), hepatic glucose output, and nonoxidative glycolysis (glycolysis minus CHO oxidation) during euglycemic-hyperinsulinemic clamping. Increasing FFA concentration (from approximately 50 to approximately 750 microM) decreased glucose uptake in a dose-dependent fashion (from approximately 9 to approximately 4 mg/kg per min). The decrease was caused mainly (approximately 2/3) by a reduction in glycogen synthesis and to a lesser extent (approximately 1/3) by a reduction in CHO oxidation. We have identified two independent defects in glycogen synthesis. The first consisted of an impairment of muscle glycogen synthase activity. It required high FFA concentration (approximately 750 microM), was associated with an increase in glucose-6-phosphate, and developed after 4-6 h of fat infusion. The second defect, which preceded the glycogen synthase defect, was seen at medium (approximately 550 microM) FFA concentration, was associated with a decrease in muscle glucose-6-phosphate concentration, and was probably due to a reduction in glucose transport/phosphorylation. In addition, FFA and/or glycerol increased insulin-suppressed hepatic glucose output by approximately 50%. We concluded that fatty acids caused a dose-dependent inhibition of insulin-stimulated glucose uptake (by decreasing glycogen synthesis and CHO oxidation) and that FFA and/or glycerol increased insulin-suppressed hepatic glucose output and thus caused insulin resistance at the peripheral and the hepatic level.

Adult↗

PubMed1994

Insulin receptor down-regulation and impaired antilipolytic action of insulin in diabetic patients after pancreas/kidney transplantation.

Patients with insulin-dependent diabetes who receive pancreas/kidney transplants lose their need for insulin injections, but they become hyperinsulinemic and insulin resistant, and sometimes develop noninsulin-dependent diabetes mellitus. The reason for the insulin resistance is not well understood. Specifically, it is not known whether they become resistant to the action of insulin on lipid metabolism. Euglycemic-hyperinsulinemic clamps were performed in six pancreas/kidney (P/K) recipients, six kidney (K) recipients (to control for immunosuppressive therapy), and eight healthy controls. Measured were leg blood flow (by plethysmography), rates of lipolysis (with [2H5] glycerol), fatty acid oxidation (by indirect calorimetry), fatty acid reesterification (with [2H5]glycerol and [1-13C]palmitate), monocyte membrane insulin binding (with [125I]Tyr-A14 insulin), and insulin receptor mass (by RIA). Fasting plasma insulin concentrations were 2 times higher in P/K and K recipients (108 pmol/L) than in controls (54 pmol/L). Insulin receptor mass in solubilized monocyte membranes from P/K and K recipients was reduced by 61% and 63%, respectively, whereas insulin binding was reduced by 73% and 70%, respectively. P/K and K recipients were resistant to the inhibitory action of insulin on lipolysis (P/K vs. controls, P < 0.01; K vs. controls, P < 0.02) and on fatty acid reesterification (P/K vs. controls, P < 0.02; K vs. controls, P < 0.03). P/K recipients appeared to be more resistant than K recipients, but the differences between the two groups were not statistically significant. We conclude that P/K recipients were hyperinsulinemic, had down-regulated the number of their monocyte insulin receptors, and were resistant to the antilipolytic action of insulin.

Adult↗

PubMed1994

Development of insulin resistance by astronauts during spaceflight.

Human spaceflight is associated with the loss of body protein. On Earth, insulin is an important factor in the regulation of muscle protein synthesis and breakdown. The objectives of this study were to determine whether insulin resistance occurs in spaceflight, and if the development of insulin resistance is related to the protein loss. The urinary C-peptide excretion rate was used as a marker for insulin secretion. The experiment was conducted before, during and after the 1991 9.5-d SLS-1 (Columbia) Space Shuttle mission. Dietary intake and urine output were monitored continuously for the four payload crewmembers from 11 d before launch to 7 d after landing for a total of 27 d. Data were obtained on the four payload crewmembers. Results were as follows: 1) the mean inflight C-peptide excretion rates were significantly lower than either the pre- or postflight rates (p < 0.05); and 2) the inflight nitrogen balance decreased as C-peptide excretion increased.

Adult↗