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Biomedical subjects

M D Jensen

Publications and source records attributed to M D Jensen.

At least 19 recordsLinked to original sources
PubMed2006

Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: effects of acute insulin withdrawal.

AIMS/HYPOTHESIS: The aim of this study was to test the hypothesis that type 1 diabetes alters renal amino acid, glucose and fatty acid metabolism. MATERIALS AND METHODS: We studied five C-peptide-negative, type 1 diabetic subjects during insulin replacement (glucose 5.6 mmol/l) and insulin deprivation (glucose 15.5 mmol/l) and compared them with six non-diabetic subjects. Leucine, phenylalanine, tyrosine, glucose and palmitate tracers were infused after an overnight fast and samples were obtained from the renal vein, femoral vein and femoral artery. RESULTS: Insulin deprivation significantly increased whole-body fluxes (20-25%) of phenylalanine, tyrosine and leucine, and leucine oxidation (50%). Kidney contributed 5-10% to the whole-body leucine and phenylalanine flux. A net uptake of phenylalanine, conversion of phenylalanine to tyrosine (5 micromol/min) and net release of tyrosine (approximately 5 micromol/min) occurred across the kidney. Whole-body (three-fold) and leg (two-fold) leucine transamination increased but amino acid metabolism in the kidney did not alter with diabetes or insulin deprivation. Insulin deprivation doubled endogenous glucose production, renal glucose production was unaltered by insulin deprivation and diabetes (ranging between 100 and 140 micromol/min). Renal palmitate exchange was unaltered by insulin deprivation. CONCLUSIONS/INTERPRETATION: In conclusion, kidney post-absorptively accounts for 5-10% of whole-body protein turnover, 15-20% of leucine transamination and 10-15% of endogenous glucose production, and actively converts phenylalanine to tyrosine. During insulin deprivation, leg becomes a major site for leucine transamination but insulin deprivation does not affect renal phenylalanine, leucine, palmitate or glucose metabolism. Despite its key metabolic role, insulin deprivation in type 1 diabetic patients does not alter many of these metabolic functions.

Amino Acids↗
PubMed2006

Computational fluid dynamics modelling of hydraulics and sedimentation in process reactors during aeration tank settling.

Aeration tank settling is a control method allowing settling in the process tank during high hydraulic load. The control method is patented. Aeration tank settling has been applied in several waste water treatment plants using the present design of the process tanks. Some process tank designs have shown to be more effective than others. To improve the design of less effective plants, computational fluid dynamics (CFD) modelling of hydraulics and sedimentation has been applied. This paper discusses the results at one particular plant experiencing problems with partly short-circuiting of the inlet and outlet causing a disruption of the sludge blanket at the outlet and thereby reducing the retention of sludge in the process tank. The model has allowed us to establish a clear picture of the problems arising at the plant during aeration tank settling. Secondly, several process tank design changes have been suggested and tested by means of computational fluid dynamics modelling. The most promising design changes have been found and reported.

Aerobiosis↗
PubMed2005

Pioglitazone increases non-esterified fatty acid clearance in upper body obesity.

AIMS/HYPOTHESIS: Plasma NEFA concentrations are largely determined by adipose tissue lipolysis. Insulin suppression of lipolysis is commonly impaired with insulin resistance and improves with thiazolidinedione treatment of type 2 diabetes. The present studies were designed to assess the effects of thiazolidinedione on NEFA (oleate) metabolism that are independent of improved glycaemic control. MATERIALS AND METHODS: We measured plasma oleate concentration and flux ([(3)H]oleate), glucose kinetics ([6-(2)H(2)]glucose) and substrate oxidation (indirect calorimetry) before and after pioglitazone (30 mg/day for approximately 20 weeks) in 20 non-diabetic adults with upper body obesity. To assess the effects of improved insulin sensitivity per se we performed the same measurements in a matched group of volunteers treated with diet/exercise. Half of the two groups underwent these measurements during a hyperinsulinaemic-euglycaemic clamp, and the other half had their measurements taken during a (control) saline infusion before and after the intervention. RESULTS: Both interventions increased insulin-stimulated glucose disposal and reduced plasma oleate concentrations during the insulin clamp. After diet/exercise, oleate flux decreased (p=0.03) during the insulin clamp and oleate clearance remained unchanged (p=0.55), whereas in the pioglitazone group, oleate flux during the clamp was unchanged (p=0.97) and oleate clearance increased (p=0.003). Oleate clearance in the saline control condition was increased in the pioglitazone group compared with the diet/exercise group (p=0.02). CONCLUSIONS/INTERPRETATION: In insulin-resistant, non-diabetic adults, pioglitazone increases NEFA clearance during physiological hyperinsulinaemia, whereas improved insulin sensitivity achieved by diet/exercise does not alter NEFA clearance but enhances insulin suppression of NEFA release. This action of pioglitazone may contribute to improved glucose metabolism in type 2 diabetes.

Adult↗
PubMed2003

Strength training for obesity prevention in midlife women.

OBJECTIVE: The primary goal of this study was to assess whether increases in fat-free mass (FFM) and decreases in total and percentage fat mass from 15 weeks of twice weekly supervised strength training would be maintained over 6 months of unsupervised exercise in a randomized controlled trial. DESIGN: In all, 60 women aged 30-50 y, body mass index between 20 and 35 kg/m(2), were randomized to control or treatment groups. The treatment group performed twice-weekly supervised strength training followed by 6 months of unsupervised training. Measurements at baseline, 15, and 39 weeks included body weight and body composition by dual-energy X-ray absorptiometry. Repeated measures regression was used to assess between-group differences for changes over time. RESULTS: Almost 90% of prescribed exercise sessions were completed. The body composition treatment effects over 15 weeks were largely maintained over 6 months of unsupervised exercise. Over the total 39 weeks of strength training, the treatment group gained +0.89 kg more in FFM, lost -0.98 kg more in fat mass, and lost -1.63% more in percent body fat when compared to the control group. P-values for these between-group differences in 39-week changes were 0.009, 0.06, and 0.006, respectively. Strength training did not result in any significant weight loss or waist circumference attenuation. Adjustment for changes in energy intake and physical activity did not alter these results. CONCLUSIONS: Twice-weekly strength training is behaviorally feasible for busy midlife women and the favorable body composition changes resulting from supervised strength training can be maintained over time. These findings lay the groundwork for determining the long-term health benefits of this behaviorally feasible exercise prescription, potentially including prevention of age-associated fat gains.

Absorptiometry, Photon↗
PubMed2003

Accelerated intramyocellular triglyceride synthesis in skeletal muscle of high-fat-induced obese rats.

OBJECTIVE: To test the hypothesis that the synthesis of intramyocellular triglycerides (imcTG) in skeletal muscle is increased in obese rats in which the content of imcTG is known to be abnormally high. ANIMALS: Sprague-Dawley male lean and high-fat-induced obese rats were studied at the age of 4, 8 and 12 months after an overnight fast, awake. MEASUREMENTS: [U-(14)C]glycerol was continuously infused intravenously for 2 h followed by muscle biopsies, and intracellular glycerol incorporation into imcTG was determined. imcTG content, intramyocellular free glycerol concentration and specific activity, systemic glycerol flux and plasma glycerol, free fatty acid (FFA) and glucose concentrations were also determined. RESULTS: The rates of incorporation of intramyocellular glycerol into imcTG (nmol/g wet muscle/h) were markedly accelerated in obese rats compared to their lean littermates at all ages: 66+/-12 vs 12+/-2 (P=0.02) for gastrocnemius and 74+/-29 vs 31+/-7 (P=0.09) for soleus when 4 months old; 223+/-29 vs 58+/-27 (P=0.001) for gastrocnemius, 224+/-28 vs 70+/-21 (P=0.001) for soleus and 294+/-78 vs 49+/-22 (P=0.02) for tibialis anterior when 8 months old; and 25+/-4 vs 11+/-2 (P=0.01) for gastrocnemius and 22+/-8 vs 8.4+/-3 (P=0.04) for soleus when 12 months old. As expected, this was accompanied by a higher imcTG content in virtually all muscles at all ages tested. CONCLUSION: The synthesis of imcTG in skeletal muscle is grossly increased in obese rats, which likely contributes to abnormal imcTG accumulation.

Adipose Tissue↗
PubMed2003

Fate of fatty acids at rest and during exercise: regulatory mechanisms.

Fatty acids are a major fuel source for humans both at rest and during exercise. Plasma free fatty acids (FFA), although present only in micromolar concentrations, are the major circulating lipid fuel. FFA availability can increase two- to four-fold with moderate intensity exercise. Other potential sources of fatty acids include circulating very low-density lipoprotein (VLDL) triglycerides (TGs) ( approximately 1/5 the fuel availability of FFA) and intramyocellular TGs ( approximately 2 mmol kg-1 muscle). At rest approximately 40% of systemic FFA uptake occurs in the splanchnic bed and uptake in legs is approximately 15-20%. During leg exercise the uptake of FFA in leg tissue increases to 30-60% of systemic uptake and splanchnic uptake decreases to 15%. The fate of VLDL TG fatty acids has not been adequately studied. Intramyocellular TG hydrolysis increases during exercise, but the factors that regulate this response are not clear. The fact that contraction of isolated muscles can stimulate the hydrolysis and oxidation of intramyocellular TGs (in the absence of hormonal or neural input) suggests an intracellular regulation of this process. Additional regulation from changes in catecholamines and insulin may also occur. During moderate intensity exercise circulating FFA and intramyocellular TG provide roughly equal portions of fatty acids for oxidation. In addition to endurance training, dietary factors have been shown to modulate the fatty acid oxidation response to exercise. Much remains to be learned about fatty acid trafficking during exercise. What role do VLDL TG play? How is the oxidation of intramyocellular TGs regulated? Techniques to address these questions in humans are only now becoming available.

Calorimetry↗
PubMed2001

Systemic and regional free fatty acid metabolism in type 2 diabetes.

To determine whether type 2 diabetes mellitus alters systemic and regional free fatty acid ([3H]palmitate) metabolism, 14 nondiabetic (ND) and 14 type 2 diabetic (D) subjects underwent hyperinsulinemic-hyperglycemic (approximately 9.3 mM) clamps. The subjects were matched for age, body mass index, percent body fat, and fat-free mass. D subjects had more (P < 0.05) visceral fat than ND. During somatostatin, replacement growth hormone, and glucagon infusions, insulin was infused to achieve moderate (approximately 75 pmol/l) and high (approximately 150 pmol/l) physiological insulin levels. D subjects had greater (P < 0.02) systemic and regional (splanchnic and leg) palmitate release than ND subjects during both insulin infusion intervals. The relative contributions of splanchnic, leg, and nonsplanchnic upper body regions to systemic palmitate release did not differ between groups, although the last contributed the most (approximately 75%) to systemic palmitate release. Visceral fat area correlated with systemic palmitate flux (r = 0.45, P < 0.03) during both insulin infusions. We conclude that type 2 diabetes is associated with a generalized impairment in insulin suppression of lipolysis compared with equally obese ND individuals.

Abdomen↗
PubMed2001

Lipid metabolism during fasting.

These studies were conducted to understand the relationship between measures of systemic free fatty acid (FFA) reesterification and regional FFA, glycerol, and triglyceride metabolism during fasting. Indirect calorimetry was used to measure fatty acid oxidation in six men after a 60-h fast. Systemic and regional (splanchnic, renal, and leg) FFA ([(3)H]palmitate) and glycerol ([(3)H]glycerol) kinetics, as well as splanchnic triglyceride release, were measured. The rate of systemic FFA reesterification was 366 +/- 93 micromol/min, which was greater (P < 0.05) than splanchnic triglyceride fatty acid output (64 +/- 6 micromol/min), a measure of VLDL triglyceride fatty acid export. The majority of glycerol uptake occurred in the splanchnic and renal beds, although some leg glycerol uptake was detected. Systemic FFA release was approximately double that usually present in overnight postabsorptive men, yet the regional FFA release rates were of the same proportions previously observed in overnight postabsorptive men. In conclusion, FFA reesterification at rest during fasting far exceeds splanchnic triglyceride fatty acid output. This indicates that nonhepatic sites of FFA reesterification are important, and that peripheral reesterification of FFA exceeds the rate of simultaneous intracellular triglyceride fatty acid oxidation.

3-Hydroxybutyric Acid↗
PubMed2001

Sources of blood glycerol during fasting.

To determine the source(s) of blood and very low density lipoprotein (VLDL)-triglyceride glycerol during fasting, four men ingested (2)H(2)O from 14 to 20 h into a 60-h fast to achieve ~0.5% body water enrichment. At 60 h of fasting, glycerol flux was measured using [2-(14)C]glycerol. Blood was taken for measurement of (2)H enrichment at carbon 6 of glucose and at carbon 3 of free glycerol and VLDL-triglyceride glycerol. (2)H enrichment of the 2 hydrogens bound to carbon 3 of VLDL-triglyceride glycerol was 105 +/- 2% of the (2)H enrichment of the 2 hydrogens bound to carbon 6 of glucose, indicating isotopic equilibrium between hepatic glyceraldehyde 3-P and glycerol 3-P. The (2)H enrichment of the 2 hydrogens bound to carbon 3 of free glycerol was 17 +/- 3% of VLDL-triglyceride glycerol, indicating that a significant percentage of free glycerol in blood originated from the hydrolysis of circulating VLDL-triglyceride or a pool of glycerol with similar (2)H enrichment. Glycerol flux was 6.3 +/- 1.1 micromol. kg(-1). min(-1). Glycerol appearing from nonadipose tissue sources was then approximately 1.1 micromol. kg(-1). min(-1). Seven other subjects were fasted for 12, 42, and 60 h. A small percentage of glycerol in the circulation after 12 h of fasting was enriched with (2)H. The enrichment of the 2 hydrogens bound to carbon 3 of free glycerol in the longer periods of fasting was approximately 16% of the enrichment of the 2 hydrogens bound to carbon 6 of glucose. Therefore, as much as 15-20% of systemic glycerol turnover during fasting is not from lipolysis of adipose tissue triglyceride.

Adult↗
PubMed2001

Physiological levels of glucagon do not influence lipolysis in abdominal adipose tissue as assessed by microdialysis.

To determine whether glucagon stimulates lipolysis in adipose tissue, seven healthy young male volunteers were studied, with indwelling microdialysis catheters placed sc in abdominal adipose tissue. Subjects were studied three times: 1) during euglucagonemia (EG; glucagon infusion rate, 0.5 ng/kg.min); 2) during hyperglucagonemia (HG; (glucagon infusion rate, 1.5 ng/kg.min); and 3) during EG and a concomitant glucose infusion mimicking the glucose profile from the day of HG (EG+G). Somatostatin (450 microg/h) was infused to suppress hormonal secretion, and replacement doses of insulin and GH were administered. Sampling was done every 30 min for 420 min. Baseline circulating values of insulin, C-peptide, glucagon, GH, glycerol, and free fatty acids were comparable in all three conditions. During EG and EG+G, plasma glucagon was maintained at fasting level (20-40 ng/L); whereas, during HG, it increased (110-130 ng/L). Interstitial concentrations of glycerol were similar in the three conditions [30,870 +/- 5,946 (EG) vs. 31,074 +/- 7,092 (HG) vs. 29,451 +/- 6,217 (EG+G) micromol/L.120 min, P = 0.98]. Plasma glycerol (ANOVA, P = 0.5) and free fatty acids (ANOVA, P = 0.3) were comparable during the different glucagon challenges. We conclude that HG per se does not increase interstitial glycerol (and thus lipolysis) in abdominal sc adipose tissue; nor does modest hyperglycemia, during basal insulinemia and glucagonemia, influence indices of abdominal sc lipolysis.

Abdomen↗
PubMed2001

Adipose tissue metabolism in benign symmetric lipomatosis.

Type 2 benign symmetric lipomatosis (BSL) is characterized by abnormal growth of adipose tissue in the upper back, deltoid region, upper arms, hips, and upper thigh region. Studies of lipomatous tissue in vitro have suggested that defective lipolysis may account for excess fat accumulation; however, in vivo adipose tissue metabolism has not been evaluated. We measured systemic adipose tissue lipolysis and regional adipose tissue fatty acid uptake in a patient with type 2 BSL scheduled for elective brachioplasty. We found increased, rather than decreased, rates of systemic free fatty acid release coupled with normal fatty acid oxidation. The uptake of fatty acids was 19% greater in deltoid region lipomatous tissue than in abdominal sc fat, whereas in control studies the relative uptake of fatty acids in deltoid fat averaged 29% less than that in abdominal fat. Adipocyte size was smaller than expected in lipomatous tissue. These results suggest that type 2 BSL is a hyperplastic adipose tissue abnormality that does not impair systemic lipolysis. The pathophysiology appears similar to what has been termed hyperplastic obesity. A better understanding of this condition could lead to insights into the mechanisms of hyperplastic obesity.

Adipose Tissue↗
PubMed2000

Metabolic complications of obesity. Pathophysiologic considerations.

Given a specific research interest in human fatty acid metabolism, this article focuses primarily on the evidence surrounding the hypothesis that dysregulation of the fuel release function of fat cells (lipolysis) is an important contributing factor to the health hazards of obesity.

Adipose Tissue↗
PubMed2000

Body composition and resting energy expenditure in humans: role of fat, fat-free mass and extracellular fluid.

OBJECTIVE: The objective of this study was to determine whether there are independent effects of extracellular fluid volume (ECF) and fat mass (FM) on resting energy expenditure (REE) relative to fat-free mass (FFM) in adult men and women. METHODS: Multiple linear regression analysis was used to relate REE, as determined by indirect calorimetry, to FFM and FM (measured using dual energy X-ray absorptiometry) and ECF (measured using bromide space and/or the radiosulfate washout space) in 153 women and 100 men with varying amounts of body fat. RESULTS: REE correlated significantly with FFM and FM in women (r=0.65 and r=0.63, both P<0.001) and men (r=0.62 and r=0.48, both P<0.001, FFM and FM, respectively). In a multiple linear regression analysis FFM, FM and age significantly contributed to the ability to predict REE in both genders. The models that were derived were not significantly different between women and men. In women the contribution to REE from FM was easier to detect when FM was greater. Adjustment of FFM for ECF did not improve the relationship between FFM and REE. CONCLUSIONS: FFM, FM and age are significant, independent predictors of REE in both men and women. Adjustment of FFM for ECF does not improve the ability of FFM to predict REE, which suggests that ECF is a highly integrated component of FFM in healthy adults. Expressing REE relative to FFM alone will introduce errors when lean and obese populations are compared.

Absorptiometry, Photon↗
PubMed2000

Energy expenditure of nonexercise activity.

BACKGROUND: We found recently that changes in nonexercise activity thermogenesis (NEAT) mediate resistance to weight gain with overfeeding in sedentary adults. A potentially important, yet seldom investigated, component of NEAT is the energy expenditure of fidgeting-like activities. OBJECTIVE: Our goal was to measure changes in energy expenditure with fidgeting-like activities. DESIGN: Energy expenditure was measured in 24 subjects (17 women and 7 men x+/- SD body weight: 76 +/- 21 kg) while recumbent at rest, sitting motionless, standing motionless, partaking of self-selected fidgeting-like movements while seated and while standing, and walking on a treadmill at 1.6, 3.2, and 4.8 km/h (1, 2, and 3 mph). Measurements were performed by using a high-precision, indirect calorimeter connected to the subject via a transparent, lightweight facemask that enabled almost unrestricted movement. RESULTS: Compared with metabolic rate in the supine position (5.4 +/- 1.5 kJ/min), energy expenditure increased while sitting motionless by 4 +/- 6%, while fidgeting while seated by 54 +/- 29% (P: < 0.0001), while standing motionless by 13 +/- 8% (P: < 0.0001), while fidgeting while standing by 94 +/- 38% (P: < 0.0001), while walking at 1.6 km/h by 154 +/- 38% (P: < 0.0001), while walking at 3.2 km/h by 202 +/- 45% (P: < 0.0001), and while walking at 4.8 km/h by 292 +/- 81% (P: < 0.0001). There was a significant, positive correlation between changes in energy expenditure and body weight for fidgeting-like activities while standing (r = 0.43, P: = 0.02) but not while seated. CONCLUSIONS: There is marked variance between subjects in the energy expenditure associated with self-selected fidgeting-like activities. The thermogenic potential of fidgeting-like and low-grade activities is sufficiently great to substantively contribute to energy balance.

Adult↗
PubMed2000

Leg free fatty acid kinetics during exercise in men and women.

We previously reported that epinephrine stimulates leg free fatty acid (FFA) release in men but not in women. The present studies were conducted to determine whether the same is true during exercise. Six men and six women bicycled for 90 min at 45% of peak O(2) consumption, during which time systemic and leg FFA kinetics ([9, 10-(3)H]palmitate) were measured. The catecholamine and hormonal responses to exercise were not different in men and women. The baseline systemic and leg palmitate release was 94 +/- 15 vs. 114 +/- 5 micromol/min and 16 +/- 2 and 20 +/- 3 micromol/min, respectively, in men and women [P = nonsignificant (NS)]. Systemic and leg palmitate release increased (both P < 0.001) to 251 +/- 18 vs. 212 +/- 16 micromol/min and 73 +/- 19 vs. 80 +/- 12 micromol/min in men and women, respectively, during the last 30 min of exercise (P = NS, men vs. women). We conclude that the systemic and leg adipose tissue lipolytic response to exercise is not different in nonobese men and women.

Adult↗
PubMed2000

Meal fatty acid uptake in human adipose tissue: technical and experimental design issues.

The adipose tissue uptake of dietary fat has been studied using fatty acid radiotracers incorporated into a meal, followed by adipose tissue biopsies. A number of experimental design issues, including the use of isotopic tracers to measure meal fatty acid oxidation and plasma appearance of tracer, as well as the heterogeneity of adipose tissue fatty acid uptake, have been addressed. We examined these questions in a study of 24 volunteers (12 men and 12 women) who consumed a meal containing [(3)H]triolein and [(14)C]triolein. Slight differences in the purity of [(3)H]triolein vs. [(14)C]triolein were found, which could affect the apparent adipose tissue uptake of meal fatty acids. The adipose tissue triglyceride specific activity from bilateral biopsy sites agreed well, implying that a unilateral biopsy is satisfactory for measuring tracer uptake. Meal fatty acid oxidation measured using [(3)H]triolein and [(14)C]triolein was well correlated (r = 0.79, P < 0.0001). The peak tracer appearance in plasma chylomicrons occurred 1 h after the ingestion of a second, unlabeled meal. Our findings have implications for the experimental design of future meal fatty acid tracer/adipose tissue biopsy studies.

Adipose Tissue↗
PubMed2000

Meal fatty acid uptake in adipose tissue: gender effects in nonobese humans.

We tested for gender differences in dietary fatty acid metabolism in 12 nonobese men and 12 nonobese women using the meal fatty acid tracer/adipose tissue biopsy study design. In addition to determining body composition, measurements of regional adipose tissue lipoprotein lipase activity, blood flow, and fat cell size were performed to place the meal fatty acid kinetic studies in perspective. Twenty-four hours after ingesting the test meal, the concentration of meal fatty acids was greater (P < 0.05) in abdominal subcutaneous than in thigh adipose tissue in both men (0. 61 +/- 0.12 vs. 0.45 +/- 0.09 mg/g) and women (0.59 +/- 0.10 vs. 0. 43 +/- 0.05) but was not different between men and women. A greater percentage of dietary fat was stored in subcutaneous adipose tissue in women than in men (38 +/- 3 vs. 24 +/- 3%, respectively, P < 0. 05), and a greater portion of meal fatty acid disposal was unaccounted for in men. Significant gender differences in regional adipose tissue blood flow after meal ingestion were noted; the differences were in the direction that could support greater nutrient storage in lower body fat in women.

Absorptiometry, Photon↗