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Biomedical subjects

J T Devlin

Publications and source records attributed to J T Devlin.

36 records · Page 2Linked to original sources
PubMed1989

Effect of tamoxifen on plasma insulin-like growth factor I in patients with breast cancer.

Human breast cancer cells secrete and have membrane receptors for insulin-like growth factor I (IGF-I), a growth hormone-dependent peptide that stimulates cell replication. However, little is known about plasma concentrations of IGF-I in breast cancer patients. Plasma IGF-I levels are decreased in malnutrition, decline with advancing age, and are influenced by estrogen. We evaluated the effect of the antiestrogen agent tamoxifen on plasma IGF-I in 32 ambulatory breast cancer patients. Treatment with tamoxifen was associated with lower concentrations of plasma IGF-I (0.48 +/- 0.3 unit/ml in treated versus 1.03 +/- 0.6 units/ml in nontreated patients, P less than 0.01). However, patients treated with tamoxifen did not differ from nontreated patients in age, menopause, duration since diagnosis, metastatic disease, recent weight loss, or measures of nutritional status. We conclude that tamoxifen therapy results in a reduction of plasma IGF-I concentration. We speculate that the antitumor action of tamoxifen in breast cancer is due in part to suppression of IGF-I.

Adult↗
PubMed1989

Whole body and regional fuel metabolism during early postexercise recovery.

We studied whole body and regional fuel metabolism 1-4 h after cycle exercise [70% maximum O2 consumption (VO2max)], using the insulin clamp technique (40 mU.M-2.min-1) with indirect calorimetry. Substrate fluxes were determined in nonexercised (forearm) muscle tissues. Total glucose utilization was not increased by exercise, either in the preinsulin or insulin-stimulated state. Glucose oxidation tended to decrease, and lipid oxidation was increased after exercise. Forearm glucose uptake (FGU) was increased 5 times by insulin in the resting state, due largely to increased fractional extraction (P less than 0.05). After exercise, FGU was not increased by insulin. Forearm alanine and lactate release was doubled 2 h after exercise. Branched-chain amino acid (BCAA) concentrations were increasing after exercise (P less than 0.01) at a time when forearm muscle was taking up these amino acids. Insulin infusion suppressed the elevated release of gluconeogenic precursors from the forearm and suppressed the elevated concentrations of BCAAs, free fatty acids, and glycerol present after exercise. In summary, basal and insulin-stimulated glucose utilization is not augmented by prior high-intensity exercise, partly because nonexercised muscle is insulin resistant. Insulin infusion attenuates the altered metabolic milieu seen during early recovery.

Adult↗
PubMed1988

Fragile sites and high-resolution chromosome studies in multiple endocrine neoplasia type 2A.

Affected individuals from four kindreds with multiple endocrine neoplasia type 2A syndrome (MEN-2A), were studied for the possible existence of a specific fragile site that might be associated with the MEN-2A gene. The chromosomes were also examined with high-resolution banding with particular emphasis on those chromosomes (#1, 10, 20, and 22) that have been implicated by previous studies from several laboratories as being associated with this disease. There was no evidence for a unique fragile site or a unique high-resolution banding pattern in subjects with MEN-2A. These findings, in combination with all previous cytogenetic studies, indicate that it is unlikely that current techniques will be useful in developing a simple cytogenetic test for this disease.

Aphidicolin↗
PubMed1988

Total suppression of cortisol excretion by ketoconazole in the therapy of the ectopic adrenocorticotropic hormone syndrome.

Ketoconazole, an antifungal imidazole derivative, has been shown to inhibit adrenal steroidogenesis in vitro and in vivo. This has led to its use clinically as an effective treatment for various forms of Cushing's syndrome. The clinically effective doses have been reported to be between 800 to 1,200 mg per day, usually without glucocorticoid replacement. Herein is reported the first case of Cushing's syndrome due to ectopic adrenocorticotropic production from a metastatic carcinoid tumor of the thymus that was treated with ketoconazole. Urinary cortisol excretion was totally suppressed at the initial dose and optimal control was achieved with relatively low doses of ketoconazole (200 to 400 mg per day), along with dexamethasone replacement. Use of glucocorticoid replacement is advisable in this setting to avoid symptomatic hypoadrenalism.

Carcinoid Tumor↗
PubMed1987

Extrapancreatic effects of L-leucine infusion in leucine-sensitive and control subjects.

We studied the extrapancreatic effects of L-leucine infusion (2.5 mumol/kg/min) in six controls (three females, three males) and three members of a family with leucine-sensitive hypoglycemia (LSH). Total glucose disposal and endogenous glucose production (EGP) rates were assessed after an overnight fast (12 to 14 hour) during somatostatin (SRIF) infusion (500 micrograms/h) with insulin replacement (0.2 mU/kg/min), combined with D-(3-3H)-glucose infusion. Additional studies of forearm arterial-venous (A-V) balances of amino acids, glucose, and other substrates, combined with L-(1-14C)-leucine kinetics, were done in these two groups. L-leucine infusion resulted in a 15% decrease in whole-body total glucose utilization in controls (P less than .05) during SRIF-insulin infusion, but did not affect glucose utilization in LSH subjects. EGP was not affected by L-leucine infusion in either group. Control subjects demonstrated a significant reduction in forearm glucose uptake and greater lactate release during L-leucine infusion, compared to the basal state. In contrast, subjects with LSH showed a slight increase in forearm glucose uptake and significantly less lactate release during L-leucine infusion. Subjects with LSH demonstrated significantly lower forearm leucine uptake, and lower rates of appearance and oxidation of L-(1-14C)-leucine during leucine infusion, compared to controls. Our data suggest that members of this LSH kindred have a defect in intracellular leucine metabolism in skeletal muscle, resulting in a lack of leucine-induced inhibition of glucose utilization. This may contribution to the development of hypoglycemia in these subjects.

Adolescent↗
PubMed1987

Enhanced peripheral and splanchnic insulin sensitivity in NIDDM men after single bout of exercise.

We studied glucose metabolism in non-insulin-dependent diabetic (NIDDM) men with and without glycogen-depleting cycle exercise 12 h beforehand and have compared the results to our previous data in lean and obese subjects. Rates of total glucose utilization, glucose oxidation, nonoxidative glucose disposal (NOGD), glucose metabolic clearance rate (MCR), and endogenous glucose production (EGP) were determined with a "two-level" insulin-clamp technique (100-min infusions at 40 and 400 mU X m-2 X min-1) combined with indirect calorimetry and D-3-[3H]glucose infusion. Muscle biopsy specimens from vastus lateralis were analyzed for glycogen content and glycogen synthase activity before and after insulin infusions. After exercise, NIDDM subjects had muscle glycogen concentrations comparable with those of lean and obese subjects. The activation of glycogen synthase both by prior exercise and insulin infusion was similar to lean controls. After exercise, total glucose disposal was significantly increased during the 40-mU X m-2 X min-1 infusion (P less than .05), but the increase observed during the 400-mU X m-2 X min-1 infusion was not significant. These increases after exercise were the result of significantly higher NOGD during both levels of insulin infusion. The MCR of glucose during both insulin infusions was reduced in NIDDM compared with lean subjects but was very similar to that in obese nondiabetics. Basal EGP was significantly reduced on the morning after exercise (4.03 +/- 0.27 vs. 3.21 +/- 0.21 mg x kg-1 fat-free mass x min-1) (P less than .05) and associated with significant reductions of fasting plasma glucose (197 +/- 12 vs. 164 +/- 9 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Potentiation of the thermic effect of insulin by exercise: differences between lean, obese, and noninsulin-dependent diabetic men.

We studied the effects of prior high-intensity cycle exercise (85% VO2 max) on total energy expenditure (EE) and the thermic effect of insulin (TEI) in normal controls and in obese insulin-resistant and noninsulin-dependent diabetic (NIDDM) subjects. Normal controls, but not obese or NIDDM subjects, showed a significant increase (3-7%) in total EE 12-16 h after exercise (p less than 0.05). Prior exercise increased lipid and decreased glucose oxidation in all groups. During low-dose insulin infusion (40 mU X M2 X min), prior exercise potentiated TEI in control and NIDDM subjects (p less than 0.05), whereas obese subjects showed no response. During high-dose insulin infusion (400 mU X M2 X min), TEI was similar in NIDDM and control subjects but was significantly less in the obese group. In this study, we found a positive correlation between TEI and insulin-stimulated rates of glucose disposal (r = 0.91, p less than 0.001). The predicted cost of glucose storage accounted for 42% of TEI.

Adult↗
PubMed1986

Effects of preexercise snack feeding on endurance cycle exercise.

We studied the effects of ingesting either a snack food (S) (260 kcal) or placebo (P) 30 min before intermittent cycle exercise at 70% maximal O2 consumption on endurance performance and muscle glycogen depletion in eight healthy human males. Immediately before exercise there were significantly greater increases in plasma glucose (PG) (S +28 +/- 9.7; P +0.1 +/- 0.8 mg/dl) and insulin (S +219 +/- 61.5; P -7 +/- 5.5 pmol/l) (P less than 0.05) following S feeding compared with P. These differences were no longer present by the end of the first exercise period. There were no differences in endurance times (S 52 +/- 6.4; P 48 +/- 5.6 min) or in the extent of muscle glycogen depletion following exercise (S 56 +/- 14.7; P 50 +/- 15.5 micrograms/mg protein) between the two groups. PG was maintained at base-line (prefeeding) concentrations following S, whereas there was a tendency for PG to steadily decrease after P. Total grams of carbohydrate oxidized during exercise did not differ between the two groups (S 120; P 118 g). These results demonstrate that the ingestion of a mixed-macronutrient snack 30 min before exercise does not impair endurance performance nor increase the extent of muscle glycogen depletion during high-intensity cycle exercise in untrained adult male subjects.

Blood Glucose↗
PubMed1985

Effects of prior high-intensity exercise on glucose metabolism in normal and insulin-resistant men.

The effects of prior high-intensity cycle exercise (85% VO2 max) to muscular exhaustion on basal and insulin-stimulated glucose metabolism were studied in obese, insulin-resistant, and normal subjects. Six obese (30.4% fat) and six lean (14.5% fat) adult males underwent two separate, two-level hyperinsulinemic-euglycemic clamp studies (100-min infusions at 40 and 400 mU/m2/min), with and without exercise 12 h earlier. Carbohydrate oxidation was estimated by indirect calorimetry using a ventilated hood system, and endogenous glucose production by D-(3-3H)-glucose infusion. Glycogen content and glycogen synthase activity (GS %l) were measured in vastus lateralis muscle biopsies before and at the end of each insulin clamp procedure. After exercise, the obese and lean subjects had comparably low muscle glycogen concentrations (0.10 versus 0.08 mg/g protein, respectively), and equal activation of muscle GS activity (54.4 versus 45.3 GS %l, respectively). In the obese subjects, insulin-stimulated glucose disposal was increased significantly, but not totally corrected to normal. In both groups there was a comparable increase in nonoxidative glucose disposal (NOGD), whereas glucose oxidation was decreased and lipid oxidation was increased. Thus, the major effect of prior exercise was to increase insulin-stimulated glucose disposal in the obese subjects and to alter the pathways of glucose metabolism to favor NOGD and decrease glucose oxidation. No correlation was found between the exercise-induced increase in GS %l and NOGD, except in the normal subjects during maximal insulin stimulation. Thus, glycogen synthase activity does not appear to be rate-limiting for NOGD at physiologic insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Characterization of immunoreactive insulin in human saliva: evidence against production in situ.

The presence of insulin immunoreactivity in extra-pancreatic tissues and fluids suggests multiple sites of insulin production. Immunoreactive insulin occurs in human saliva and concentrations increase after oral glucose ingestion. The goal of these experiments was to determine whether the presence of immunoreactive insulin in this extra-pancreatic site is independent of pancreatic production or merely represents the accumulation of circulating pancreatic insulin. The mean +/- SEM concentration of extracted salivary immunoreactive insulin in five normal volunteers increased during an oral glucose tolerance test from basal values of 36 +/- 3.0 to 291 +/- 40 pmol/l; however, the peak occurred 45-90 min later than in serum. On this basis, it was not possible to distinguish between the stimulation (by increased blood glucose concentrations) of insulin synthesis in the saliva glands from the accumulation of blood insulin. Therefore, we studied a group of five volunteers during intravenous infusion of insulin (1 and 10 mU X kg-1 X min-1, sequentially) and glucose (euglycaemic clamp). Under these conditions, salivary immunoreactive insulin concentrations increased significantly from 254 +/- 100 to 1919 +/- 437 pmol/l (p less than 0.05), while simultaneous mean plasma C-peptide concentrations were unchanged. Thus, the concentration of salivary immunoreactive insulin was clearly related to the amount of insulin in the blood and not to the plasma glucose concentration. Physico-chemical and immunological characterization of salivary immunoreactive insulin by dilution in radioimmunoassay, gel filtration and polyacrylamide disc gel electrophoresis demonstrated that the majority of it was indistinguishable from insulin standards.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗