Biomedical subjects

A L Castle

Publications and source records attributed to A L Castle.

9 recordsLinked to original sources

PubMed1999

Attenuating the decline in ATP arrests the exercise training-induced increases in muscle GLUT4 protein and citrate synthase activity.

Thirty-two female Sprague-Dawley rats were assigned to one of four groups: control (CON); exercise training (TR); exercise training + clenbuterol treatment (0.8 mg kg body wt(-1) d(-1)) (TR + CL) or exercise training + clenbuterol treatment + 2% beta-guanidinoproprionic acid diet (TR + CL + beta) to examine whether alterations in the high energy phosphate state of the muscle mediates exercise training-induced increases in skeletal muscle GLUT4 protein concentration and citrate synthase activity. Exercise training consisted of running the rats 5 d week(-1) for 8 weeks on a motor-driven treadmill (32 m min(-1), 15% grade). Gastrocnemius GLUT4 protein concentration and citrate synthase activity were significantly elevated in the TR animals, but these adaptations were attenuated in the TR + CL animals. Providing beta-GPA in combination with clenbuterol enabled training to elevate GLUT4 protein concentration and citrate synthase activity, with the increase in GLUT4 being greater than that observed for the TR animals. Skeletal muscle ATP levels were reduced in the TR + CL + beta animals while ATP levels in the TR + CL animals were significantly elevated compared with CON. An acute 40-min bout of electrical stimulation of the sciatic nerve was found to lower skeletal muscle ATP levels by approximately 50% and elevate cAMP levels in all groups. No difference in post-contraction cAMP levels were observed among groups. However, post-contraction ATP levels in the TR + CL animals were significantly greater than the other groups. Collectively, these findings suggest that exercise training-induced increases in skeletal muscle GLUT4 protein concentration and citrate synthase activity are initiated in response to a reduction in the skeletal muscle ATP concentration.

Adenosine Triphosphate↗

PubMed1998

Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue.

Type 2 diabetes is a complex metabolic disorder characterized by peripheral insulin resistance and impaired beta cell function. Insulin resistance is inherited as a non-mendelian trait. In genetically predisposed individuals, resistance of skeletal muscle and adipose tissue to insulin action precedes the onset of clinical diabetes, and is thought to contribute to hyperglycaemia by leading to impaired beta cell function and increased hepatic glucose production. It is not clear whether beta cell and liver defects are also genetically determined. To test the hypothesis that insulin resistance in muscle and fat is sufficient to cause type 2 diabetes in the absence of intrinsic beta cell and liver abnormality, we generated transgenic mice that were insulin-resistant in skeletal muscle and adipose tissue. These mice developed all the prodromal features of type 2 diabetes but, despite the compounded effect of peripheral insulin resistance and a mild impairment of beta cell function, failed to become diabetic. These findings indicate the need for a critical re-examination of the primary site(s) of insulin resistance in diabetes.

Adipose Tissue↗

PubMed1998

Effect of chronic electrical stimulation and beta-GPA diet on GLUT4 protein concentration in rat skeletal muscle.

The present study investigated whether alterations in the muscle high energy phosphate state initiates the contraction-induced increase in skeletal muscle GLUT4 protein concentration. Sprague-Dawley rats were provided either a normal or a 2% beta-guanidinoproprionic acid (beta-GPA) diet for 8 weeks and then the gastrocnemius of one hind limb was subjected to 0, 14 or 28 days of chronic (24 h day-1) low-frequency electrical stimulation (10 Hz). The beta-GPA diet, in the absence of electrical stimulation, significantly reduced ATP, creatine phosphate, creatine and inorganic phosphate and elevated GLUT4 protein concentration by 60% without altering adenylate cyclase activity or cAMP concentration. Following 14 days of electrical stimulation, GLUT4 protein concentration was elevated above non-stimulated muscle in both groups but was significantly more elevated in the beta-GPA group. Concurrent with this greater rise in GLUT4 protein concentration was a greater decline in the high energy phosphates and a greater rise in cAMP. After 28 days of electrical stimulation, GLUT4 protein concentration and cAMP stabilized and was not different between diet treatments. However, the high energy phosphates were significantly higher in the normal diet rats as opposed to the beta-GPA rats. These findings therefore suggest that a reduction in cellular energy supply initiates the contraction-induced increase in muscle GLUT4 protein concentration, but that a rise in cAMP may potentiate this effect.

Adenosine Triphosphate↗

PubMed1998

Amylin influences insulin-stimulated glucose metabolism by two independent mechanisms.

The effects of amylin on fiber type-specific muscle glucose metabolism under hyperglycemic (10 mmol/l) and hyperinsulinemic (2.1 nmol/l) conditions were investigated using a rat hindlimb perfusion system. Amylin concentration ranged from 1 to 100 nM. Efficacy for inhibition of glucose uptake traced with 2-deoxyglucose by amylin was demonstrated in all three fiber types. The incorporation of 2-deoxy-[3H]glucose tracer decreased from control values by 41% in fast oxidative (FO), 36% in fast glycolytic (FG), and 37% in slow oxidative (SO) muscle with 100 nM amylin. Amylin increased intracellular glucose 6-phosphate (G-6-P), and G-6-P was negatively correlated with 2-deoxyglucose uptake in both FO (r = -0.65; P < 0.01) and FG (r = -0.53; P < 0.01) muscle. Muscle glycogen concentration increased under control conditions and decreased in the presence of 100 nM amylin. Lactate arteriovenous efflux across the hindlimb increased significantly above control with 100 nM amylin (5.03 +/- 0.81 to 11.28 +/- 0.94 mumol.g-1.h-1). Adenosine 3',5'-cyclic monophosphate (cAMP) increased in FO and FG muscle with amylin. Salmon calcitonin-(8-32), an amylin antagonist, ameliorated the effect of amylin on all responses other than 2-deoxyglucose uptake and G-6-P concentration. These results suggest that amylin may work through at least two independent mechanisms, a cAMP-mediated effect on glycogen metabolism and a non-cAMP-mediated inhibition of glycolysis.

Amyloid↗

PubMed1998

Amylin-mediated inhibition of insulin-stimulated glucose transport in skeletal muscle.

We examined the effects of amylin on 3-O-methyl-D-glucose (3-O-MG) transport in perfused rat hindlimb muscle under hyperinsulinemic (350 microU/ml, 2,100 pmol/l) conditions. Amylin at 100 nmol/l concentration inhibited 3-O-MG transport relative to control in all three basic muscle fiber types. Transport decreased in slow-twitch oxidative (from 5.65 +/- 1.13 to 3.46 +/- 0.71 micromol . g-1 . h-1), fast-twitch oxidative (from 6.84 +/- 0.90 to 4.84 +/- 0.76 micromol . g-1 . h-1), and fast-twitch glycolytic (from 1.27 +/- 0.20 to 0.60 +/- 0.05 micromol . g-1 . h-1) muscle. Amylin inhibition of insulin-stimulated glucose transport in skeletal muscle was accompanied by a 433 +/- 72% increase in intracellular glucose 6-phosphate (G-6-P) despite the absence of extracellular glucose. The source of hexose units for the formation and maintenance of G-6-P was likely glycogen. Amylin increased glycogenolysis, increased lactate formation, and decreased glycogen synthase activity. Furthermore, the kinetics of glycogen synthase suggest that this enzyme may control intracellular G-6-P concentration. Despite the large increase in G-6-P, no detectable increase in uridine diphosphate-N-acetylhexosamines occurred, suggesting that the proposed glucosamine pathway may not be involved in transport inhibition. However, decreases in uridine diphosphate hexoses were detected. Therefore, uridine or hexosamine-based metabolites may be involved in amylin action.

3-O-Methylglucose↗

PubMed1998

The challenges of dental laboratory technology education: will it survive?

Accredited formal educational programs in dental laboratory technology are now under pressures at levels they have never undergone before. Already pushed to the point where many have had to close their doors, the remainder are struggling to survive with already strained resources. Whether or not they will be able to maintain their existence will depend upon their ability to attract quality students, provide them with a good, up to date education, and do so with ever increasing efficiency.

Curriculum↗

PubMed1997

Chromium and exercise training: effect on obese women.

Chromium supplementation may affect various risk factors for coronary artery disease (CAD) and non-insulin-dependent diabetes mellitus (NIDDM), including body weight and composition, basal plasma hormone and substrate levels, and response to an oral glucose load. This study examined the effects of chromium supplementation (400 micrograms.d-1), with or without exercise training, on these risk factors in young, obese women. Chromium picolinate supplementation resulted in significant weight gain in this population, while exercise training combined with chromium nicotinate supplementation resulted in significant weight loss and lowered the insulin response to an oral glucose load. We conclude that high levels of chromium picolinate supplementation are contraindicated for weight loss in young, obese women. Moreover, our results suggest that exercise training combined with chromium nicotinate supplementation may be more beneficial than exercise training alone for modification of certain CAD and NIDDM risk factors.

Adolescent↗

PubMed1997

Contraction-induced intracellular signals and their relationship to muscle GLUT-4 concentration.

This investigation used a model of increased skeletal muscle contractile activity to evaluate whether the adenylate cyclase-adenosine 3',5'-cyclic monophosphate (cAMP) pathway and/or the high-energy phosphate state of the muscle might be temporally related to the contraction-induced increase in skeletal muscle GLUT-4 protein concentration. Plantaris and gastrocnemius muscles of Sprague-Dawley rats were subjected to 3, 7, 14, or 28 days of chronic low-frequency electrical stimulation (10 Hz, 24 h/day). GLUT-4 protein concentration was slightly reduced after 3 days of electrical stimulation, similar to control values at 7 days and significantly elevated above control at 14 days (53%, P < 0.05) and 28 days (338%, P < 0.05) of stimulation. ATP, creatine phosphate, creatine, and P, were inversely related to GLUT-4 protein concentration. Adenylate cyclase activity increased with electrical stimulation and was significantly related to the increased GLUT-4 protein. cAMP was significantly increased at 14 days of stimulation and remained elevated through 28 days. These results demonstrate that both the adenylate cyclase-cAMP pathway and the high-energy phosphate state of the muscle are temporally related to elevations in skeletal muscle GLUT-4 protein concentration in response to chronic low-frequency electrical stimulation and, as such, suggest that both may comprise a component of the intracellular signal that regulates the contraction-induced increase in skeletal muscle GLUT-4 protein concentration.

Adenylyl Cyclases↗

PubMedDate not supplied

Comparing vertical dimension changes with and without a face-bow transfer.

The purpose of this investigation was to identify any difference of vertical dimension change that could be attributed to not using a face-bow transfer. Both demonstrations resulted in occlusal changes in vertical dimension. In comparing the demonstrations, where a hinge axis transfer was not taken, a greater amount of change was recorded over that observer in the demonstration where the hinge axis transfer was made. More dedicated research is clearly warranted to establish how much of the change was due to normal technical error. The time spent taking a face-bow transfer (hinge axis) may represent a small portion of the time required to accomplish adjustments on a denture where no transfer was performed. This information will allow the clinician to decide on the time they are willing to dedicate to occlusal corrections at the chair.

Dental Articulators↗