Search PubMed⌕ Search

Biomedical subjects

M D Jensen

Publications and source records attributed to M D Jensen.

At least 109 records · Page 6Linked to original sources
PubMed1991

Effects of glucagon on free fatty acid metabolism in humans.

To determine whether physiological changes in plasma glucagon concentrations are important in regulating basal adipose tissue lipolysis, FFA flux ([1-14C]palmitate) was measured in response to increases and decreases in plasma glucagon. Eight volunteers with insulin-dependent diabetes mellitus (IDDM) and nine healthy nondiabetic volunteers were studied using the pancreatic clamp technique to control plasma insulin, GH, and glucagon concentrations at desired levels. Palmitate flux at the chosen euglucagonemic hormone infusion rates was similar to baseline values (1.73 +/- 0.12 vs. 1.75 +/- 0.23 and 1.35 +/- 0.18 vs. 1.35 +/- 0.16 mumol/kg.min, respectively, in IDDM and nondiabetic subjects). No significant changes in palmitate flux occurred in response to glucagon withdrawal or mild (nondiabetic volunteers) or high physiological (IDDM volunteers) hyperglucagonemia. Thus, under conditions of normal FFA availability, changes in plasma glucagon concentrations within the physiological range have little or no effect on adipose tissue lipolysis.

Adipose Tissue↗
PubMed1991

Stimulation of lipolysis in humans by physiological hypercortisolemia.

The effect of glucocorticoids on adipose tissue lipolysis in animals and humans is controversial. To determine whether a physiological increase in plasma cortisol, similar to that observed in diabetic ketoacidosis and other stress conditions, stimulates lipolysis, palmitate kinetics were measured in seven nondiabetic volunteers on two occasions with [1-14C]palmitate as a tracer. Subjects received a 6-h infusion of either 2 micrograms.kg-1.min-1 hydrocortisone or saline in random order. On both occasions, a pancreatic clamp (0.12 micrograms.kg-1.min-1 somatostatin, 0.05 mU.kg-1.min-1 insulin, and 3 ng.kg-1.min-1 growth hormone) was used to maintain plasma hormone concentrations at desired levels. Plasma cortisol concentrations increased to approximately 970 nM during cortisol infusion. Palmitate rate of appearance (Ra) and concentration increased by approximately 60% during cortisol infusion but did not change during saline infusion. Increments in palmitate Ra and concentration over the 6-h study were significantly greater during cortisol than saline infusion when compared by area-under-the-curve analysis (152 +/- 52 vs. -48 +/- 23 mumol.kg-1 and 12.2 +/- 4.1 vs. -4.9 +/- 4.1 mmol.min-1.L-1, respectively; P less than 0.02). Plasma glucose concentrations did not change significantly during cortisol (5.0 +/- 0.3 vs. 6.1 +/- 0.6 mM, NS) or saline (4.9 +/- 0.2 vs. 4.9 +/- 0.1 mM, NS) infusion. In nondiabetic volunteers, a 6-h cortisol infusion was associated with a 60% increase in palmitate Ra that did not occur with saline infusion. Thus, physiological hypercortisolemia may contribute to the increased rates of lipolysis observed in humans during stress.

Adult↗
PubMed1990

Measurement of non-steady-state free fatty acid turnover.

The accuracy of non-steady-state equations for measuring changes in free fatty acid rate of appearance (Ra) is unknown. In the present study, endogenous lipolysis (traced with [14C]-linoleate) was pharmacologically suppressed in six conscious mongrel dogs. A computer-responsive infusion pump was then used to deliver an intravenous oleic acid emulsion in both constant and linear gradient infusion modes. Both non-steady-state equations with various effective volumes of distribution (V) and steady-state equations were used to measure oleate Ra [( 14C]oleate). Endogenous lipolysis did not change during the experiment. When oleate Ra increased in a linear gradient fashion, only non-steady-state equations with a large (150 ml/kg) V resulted in erroneous values (9% overestimate, P less than 0.05). In contrast, when oleate Ra decreased in a similar fashion, steady-state and standard non-steady-state equations (V = plasma volume = 50 ml/kg) overestimated total oleate Ra (18 and 7%, P less than 0.001 and P less than 0.05, respectively). Overall, non-steady-state equations with an effective V of 90 ml/kg (1.8 x plasma volume) allowed the most accurate estimates of oleate Ra.

Animals↗
PubMed1990

Lack of effect of hyperglycemia on lipolysis in humans.

Controversy exists regarding whether plasma glucose concentrations are independently involved in the regulation of adipose tissue lipolysis. In the present study, six subjects with insulin-dependent diabetes and six nondiabetic volunteers were studied during infusion of somatostatin, growth hormone, and insulin at rates designed to maintain basal rates of lipolysis, which was traced using a constant infusion of [1-14C]palmitate. A euglycemic (approximately 5 mmol/l) clamp was performed for 3 h, followed by 3 h of hyperglycemia (approximately 9 and approximately 11 mmol/l in nondiabetic and diabetic subjects, respectively). Ten nondiabetic subjects were studied during 6 h of euglycemia to exclude time-dependent changes in lipolysis. The results showed that palmitate concentrations did not change between euglycemia and hyperglycemia in either group [118 +/- 10 vs. 132 +/- 14 mumol/l and 145 +/- 21 vs. 134 +/- 15 mumol/l in nondiabetic and diabetic subjects, respectively; both P = not significant (NS)]. Similarly, palmitate rate of appearance (Ra) did not change during hyperglycemia (1.0 +/- 0.1 and 1.7 +/- 0.4 mumol.kg-1.min-1 in nondiabetic and diabetic subjects, respectively) compared with euglycemia (1.0 +/- 0.1 and 1.6 +/- 0.4 mumol.kg-1.min-1 in nondiabetic and diabetic subjects, respectively; P = NS). Palmitate concentrations and Ra did not change during 6 h of euglycemia in nondiabetic volunteers. Thus hyperglycemia per se has no effect on free fatty acid turnover. Changes in lipolysis that occur coincident with hyperglycemia are probably due to changes in other circulating substrates or hormones known to affect lipolysis.

Adult↗
PubMed1989

Influence of body fat distribution on free fatty acid metabolism in obesity.

UNLABELLED: In order to determine whether differences in body fat distribution result in specific abnormalities of free fatty acid (FFA) metabolism, palmitate turnover, a measure of systemic adipose tissue lipolysis, was measured in 10 women with upper body obesity, 9 women with lower body obesity, and 8 nonobese women under overnight postabsorptive (basal), epinephrine stimulated and insulin suppressed conditions. RESULTS: Upper body obese women had greater (P less than 0.005) basal palmitate turnover than lower body obese or nonobese women (2.8 +/- 0.2 vs. 2.1 +/- 0.2 vs. 1.8 +/- 0.2 mumol.kg lean body mass (LBM)-1.min-1, respectively), but a reduced (P less than 0.05) net lipolytic response to epinephrine (59 +/- 7 vs. 79 +/- 5 vs. 81 +/- 7 mumol palmitate/kg LBM, respectively). Both types of obesity were associated with impaired suppression of FFA turnover in response to euglycemic hyperinsulinemia compared to nonobese women (P less than 0.005). These specific differences in FFA metabolism may reflect adipocyte heterogeneity, which may in turn affect the metabolic aberrations associated with different types of obesity. These findings emphasize the need to characterize obese subjects before studies.

Adipose Tissue↗
PubMed1989

Insulin regulation of lipolysis in nondiabetic and IDDM subjects.

To determine whether insulin regulation of lipolysis is abnormal in subjects with poorly controlled insulin-dependent diabetes mellitus (IDDM), free-fatty acid flux ([1-14C]palmitate) was measured under conditions ranging from complete insulin withdrawal to hyperinsulinemia. Seven nondiabetic and seven IDDM subjects were studied with the pancreatic clamp technique to control plasma insulin, growth hormone, and glucagon concentrations at the desired levels. Preliminary studies were performed to validate the experimental design. The palmitate flux response to insulin withdrawal (2.5 +/- 0.2 vs. 2.5 +/- 0.2 mumol.kg-1.min-1) and maximally antilipolytic insulin concentrations (0.17 +/- 0.02 vs. 0.23 +/- 0.03 mumol.kg-1.min-1) were not different in nondiabetic and IDDM subjects, respectively. In contrast, IDDM subjects required significantly greater plasma free-insulin concentrations to result in equivalent suppression of palmitate flux compared with nondiabetic subjects. Lipolysis was found to be very sensitive to insulin in nondiabetic humans, with half-maximal suppression occurring at plasma free-insulin concentrations of approximately 12 pM (less than 2 microU/ml). We conclude that adipose tissue lipolysis is normally exquisitely sensitive to insulin and that sensitivity, but not responsiveness to insulin, is impaired in poorly controlled IDDM.

Adult↗
PubMed1988

Measurement of body potassium with a whole-body counter: relationship between lean body mass and resting energy expenditure.

We conducted studies to determine whether the Mayo whole-body counter could be used to measure body potassium, and thus lean body mass (LBM), and whether moderate obesity alters resting energy expenditure when corrected for LBM. Twenty-four nonobese and 18 moderately obese adults underwent body potassium (40K) counting, as well as tritiated water space measurement and indirect calorimetry. LBM values predicted from 40K counting and tritiated water space measurements were highly correlated (P = 0.001; r = 0.88). Resting energy expenditure was closely related to LBM (P less than 0.0001; r = 0.78): kcal/day = 622 kcal + (LBM.20.0 kcal/kg LBM). In this relationship, the obese subjects did not differ from nonobese subjects. In summary, the Mayo whole-body counter can accurately measure LBM, and moderate obesity has no detectable effect on corrected resting energy expenditure.

Adult↗
PubMed1988

Choice of infusion-sampling mode for tracer studies of free fatty acid metabolism.

To determine the preferred infusion-sampling mode for isotopic studies of free fatty acid (FFA) metabolism, tracer [( 14C]palmitate) was infused into the left ventricle of five anesthetized dogs, and tracee ([3H]palmitate) was infused into three separate peripheral veins of each dog. The [14C]palmitate specific activity (SA) was lower in mixed venous than arterial blood, and [3H]palmitate SA was equal in both sites. The actual infusion rate of [3H]palmitate [2.15 +/- 0.31 X 10(5) disintegrations/min (dpm).kg-1.min-1] could be accurately predicted (2.14 +/- 0.32 X 10(5) dpm.kg-1.min-1) using the known [14C]palmitate infusion rate and the arterial plasma [14C]-to-[3H]palmitate ratio. In contrast, the mixed venous [14C]-to-[3H]palmitate ratio resulted in overestimates (P less than 0.05) of the actual [3H]palmitate infusion rate. In summary, venous tracer infusion with arterial blood sampling for FFA tracer studies provides the most accurate estimates of tracee rate of appearance.

Animals↗
PubMed1988

Preservation of insulin effects on glucose production and proteolysis during fasting.

To determine whether fasting alters the ability of insulin to suppress endogenous glucose production or proteolysis, isotopic flux measurements of glucose, leucine, alpha-keto-isocaproate, and alanine were made in 13 normal volunteers after a 14-h (day 1) and an 84-h (day 4) fast. Using the "pancreatic clamp" technique, we achieved small increments in plasma insulin concentrations, as well as constant and identical plasma hormone and glucose concentrations, on both study days in seven subjects. The remaining six subjects were infused with saline and served as controls. Leucine rate of appearance (an index of proteolysis) was greater on day 4 than on day 1 (P less than 0.001), but decreased to equal values during the pancreatic clamp on each study day. During the pancreatic clamp, endogenous glucose production decreased to lesser (P less than 0.005) values on day 4 than on day 1. In conclusion, insulin suppresses proteolysis equally well before and after brief fasting, and endogenous glucose production is more completely suppressed by insulin after brief fasting than after an overnight fast.

Adult↗
PubMed1987

Intragastric balloons in comparison with standard therapy for obesity--a randomized, double-blind trial.

Intragastric balloons are new but commonly used devices for the treatment of obesity; however, their safety and efficacy have not been established. We report our results of a small, double-blind, randomized trial in which the effectiveness of intragastric balloons was compared with that of conventional medical therapy for obesity. Twenty-two patients, who were 21 to 77% over ideal body weight, were studied. Eleven underwent insertion of an intragastric balloon, and 11 underwent sham procedures. One patient with a gastric balloon withdrew from the study after 3 days. Weight loss at 2 to 3 months in the conventional therapy group averaged 2.8 kg; in the balloon-treated group, the mean weight loss was 5.8 kg (P greater than 0.15). Of the 10 balloons, 8 spontaneously deflated, and 1 was passed in the stools. We noted gastric erosions in five patients and multiple gastric ulcers in one. We conclude that the intragastric balloon was not clearly effective in inducing weight loss, had a high rate of spontaneous deflation, and was damaging to the gastric mucosa. Controlled trials should be done before similar weight-reduction devices are used in routine clinical practice.

Adult↗
PubMed1987

Validation of a new method for determination of free fatty acid turnover.

The accuracy of tracer methods for estimating free fatty acid (FFA) rate of appearance (Ra), either under steady-state conditions or under non-steady-state conditions, has not been previously investigated. In the present study, endogenous lipolysis (traced with 14C palmitate) was suppressed in six mongrel dogs with a high-carbohydrate meal 10 h before the experiment, together with infusions of glucose, propranolol, and nicotinic acid during the experimental period. Both steady-state and non-steady-state equations were used to determine oleate Ra ([3H]oleate) before, during, and after a stepwise infusion of an oleic acid emulsion. Palmitate Ra did not change during the experiment. Steady-state equations gave the best estimates of oleate inflow approximately 93% of the known oleate infusion rate overall, while errors in tracer estimates of inflow were obtained when non-steady-state equations were used. The metabolic clearance rate of oleate was inversely related to plasma concentration (P less than 0.01). In conclusion, accurate estimates of FFA inflow were obtained when steady-state equations were used, even under conditions of abrupt and recent changes in Ra. Non-steady-state equations, in contrast, may provide erroneous estimates of inflow. The decrease in metabolic clearance rate during exogenous infusion of oleate suggests that FFA transport may follow second-order kinetics.

Animals↗
PubMed1987

Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine.

These studies were designed to determine whether the insulin resistance of fasting extends to its antilipolytic effects and whether fasting enhances the lipolytic effects of adrenergic stimulation independent of changes in plasma hormone and substrate concentrations. Palmitate flux was determined isotopically ([1-14C]palmitate) before and during epinephrine infusion in normal volunteers after a 14-h (day 1) and an 84-h (day 4) fast. Using a pancreatic clamp, constant plasma hormone and glucose concentrations were achieved on both study days in seven subjects. Six subjects were infused with saline and served as controls. During the pancreatic clamp, palmitate flux was greater (P less than 0.01) on day 4 than day 1, despite similar plasma insulin, glucagon, growth hormone, cortisol, epinephrine, norepinephrine, and glucose concentrations. The lipolytic response to epinephrine was greater (P less than 0.05) on day 4 than day 1 in both groups of subjects. In conclusion, lipolysis during fasting is less completely suppressed by insulin and more readily stimulated by epinephrine.

Adult↗
PubMed1986

The roles of diet and exercise in the management of patients with insulin-dependent diabetes mellitus.

Current dietary recommendations for patients with diabetes are similar to those for the US population in general, including a moderate intake of sucrose. Awareness of the carbohydrate content of meals will allow adjustments of the dose of meal-related short-acting insulin when the size of the meal is altered; thus, meal planning can be flexible without sacrificing glycemic control. Although exercise may have potential benefits for patients with diabetes, it is also associated with greater risk in these persons than in their nondiabetic counterparts and frequently complicates the management of their disease. If there are no contraindications to regular, vigorous exercise and the patient desires to participate, careful self-monitoring of blood glucose, combined with snacks and insulin dose adjustment, should enable the intensively treated patient to exercise safely.

Absorption↗
PubMed1986

Complications of insulin-dependent diabetes mellitus: management of insulin reactions and acute illness.

Occasional mild hypoglycemia is an unavoidable and usually acceptable side effect of intensive insulin therapy. Patients with insulin-dependent diabetes mellitus may have impaired glucose counterregulation, which may increase the risk of hypoglycemia and justify less ambitious glycemic goals. A conservative but flexible approach to the treatment of insulin reactions is appropriate in order to avoid hyperglycemia. Insulin requirements are often increased during acute illness, and frequent self-monitoring of blood glucose concentrations is necessary to determine the need for supplementation with regular insulin. Frequent supplementation, together with modification of diet and maintenance of fluid intake, should not only minimize the need for hospitalization but also prevent severe deterioration in glycemic control.

Acute Disease↗
PubMed1986

Lymphocytic hypophysitis with isolated corticotropin deficiency.

In a 32-year-old woman, acquired, isolated corticotropin deficiency resulted from postpartum lymphocytic hypophysitis. The literature suggests that lymphocytic hypophysitis may cause acquired deficiencies of anterior, and possibly posterior, pituitary hormones. Immunologic evaluation of our patient failed to uncover anticorticotroph antibodies. Prompt recognition of this potentially fatal condition is important because of the availability of effective treatment.

Adrenocorticotropic Hormone↗