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Biomedical subjects

R J Howland

Publications and source records attributed to R J Howland.

12 recordsLinked to original sources
PubMed1991

Gastric inhibitory polypeptide and insulin responses to orally administered amino acids in genetically obese hyperglycemic (ob/ob) mice.

The effects of oral administration of eight L-amino acids (alanine, arginine, cysteine, glycine, histidine, hydroxyproline, lysine and threonine) individually or as an amino acid mixture on plasma gastric inhibitory polypeptide (GIP), insulin and glucose concentrations were examined in 18-h fasted obese hyperglycemic (ob/ob) mice. At a dose of 5.4 mmol/kg body weight, arginine, cysteine, histidine and the amino acid mixture were equipotent in terms of increasing plasma GIP and insulin concentrations. Alanine, hydroxyproline and lysine also increased plasma GIP, but insulin concentrations were unchanged. In contrast, threonine failed to affect either GIP or insulin concentrations. There was no correlation between either the incremental or integrated GIP and insulin responses, and none of the amino acids administered affected circulating glucose concentrations. The results indicate that a range of essential and nonessential neutral and basic amino acids stimulate the release of GIP in ob/ob mice. However, GIP made only a modest contribution to the stimulation of insulin secretion following administration of amino acids in the presence of basal glycemia.

Administration, Oral↗
PubMed1987

Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat.

1. The effects of insulin (2 nM and 4 nM) upon oxygen consumption (VO2), lipolysis rates and indirectly derived rates of fatty acid utilization, by isolated brown adipocytes from warm-acclimated (W cells) and cold-acclimated (C cells) animals, induced by noradrenaline and glucagon separately and conjointly, are reported. 2. Changes in interrelationships (coupling) between the parameters under different treatment regimes were assessed using bivariate regression analyses. 3. Administration of glucagon with noradrenaline increased lipolysis/fatty acid utilization coupling without concomitant increase of VO2 suggesting that glucagon may increase re-esterification through glycogenolytic generation of glycerol 3-phosphate, trapping intracellular fatty acid in excess of the capacity of disposal mechanisms, thus conserving respiratory substrate. 4. W cells were unresponsive to glucagon in terms of lipolysis and VO2, C cells responded to glucagon with parallel increases in lipolysis rate and VO2. Both cell types responded to noradrenaline alone and conjointly with glucagon; C cells were more sensitive to these agonists than W cells. 5. Lipolysis/VO2 coupling was reduced in C cells suggesting that in cold acclimation, noradrenaline-induced lipolysis rates are in excess of the capacity of cellular oxidation/re-esterification mechanisms. 6. Insulin inhibited noradrenaline and glucagon-induced lipolysis, simultaneously increasing VO2, supporting the hypothesis that glucose may be a thermogenic substrate in brown adipase tissue, permitting concurrent thermogenesis and lipogenesis. C cells were more insulin-sensitive than W cells. 7. The data indicate that insulin may mediate its effects (additively with noradrenaline) by activation of pyruvate dehydrogenase, generating glycolytic flux and, in the presence of noradrenaline-inhibited lipogenesis, generate additional oxaloacetate, permitting increased beta-oxidation.

Acclimatization↗
PubMed1986

Differential effects of noradrenaline and glucagon on lipolysis and fatty-acid utilization in brown adipose tissue.

The relative effects of noradrenaline (300 pM-3 microM) and glucagon (30 pM-300 nM) upon lipolysis and fatty acid utilization rates in brown adipose tissue from warm- (WA) and cold-acclimated (CA) rats, were: lipolytic sensitivity and responsiveness to the agonists were reduced in CA tissue; in CA tissue, at 300 pM, glucagon promoted fatty acid utilization more than noradrenaline; glucagon at 300 pM increased fatty acid utilization in WA tissue. The data suggest that glucagon has a physiological role in brown adipose tissue, modulating events subsequent to NA- and glucagon-induced lipolysis, promoting fatty acid utilization.

Acclimatization↗
PubMed1986

Acute cold exposure increases the glucagon sensitivity of thermogenic metabolism in the rat.

Administration of glucagon to rats at 25 degrees C had no effect upon their VO2, while administration of noradrenaline or noradrenaline plus glucagon raised the VO2. At 5 degrees C, noradrenaline had no effect upon the cold-enhanced VO2, while glucagon caused a rise of 13.7%, implying increased glucagon sensitivity at 5 degrees C. The glucagon-induced enhancement of VO2 was abolished by concurrent administration of noradrenaline.

Animals↗
PubMed1986

Adaptive changes in insulin and glucagon secretion during cold acclimation in the rat.

Arginine-stimulated insulin and glucagon outputs from isolated perfused pancreata of warm-acclimated and 2-, 4-, and 6-wk cold-acclimated rats (4 degrees C) were determined to assess whether observed changes in these parameters were a result of cold exposure per se or a part of the adaptive process of cold acclimation. Progressive and sequential changes were seen in both insulin and glucagon outputs. At 2 wk cold acclimation, glucagon rose and insulin output tended to fall, at 4 wk, glucagon output remained elevated and insulin output was further reduced, and at 6 wk, glucagon output had returned to control levels, whereas insulin output was substantially further reduced. These changes resulted in reduction of the insulin-to-glucagon molar ratio of the total arginine-induced output from 7.27 +/- 1.76 (SE) in the warm acclimate to 2.31 +/- 0.79 (SE) at 2 wk, 1.42 +/- 0.29 (SE) at 4 wk, and 1.26 +/- 0.21 (SE) at 6 wk cold acclimation. The data do not provide in vitro support for the hypothesis that changes in pancreatic hormone secretion in vivo are a consequence of cold exposure and not cold acclimation.

Acclimatization↗
PubMed1985

A high-precision automatic closed-circuit respirometer for small animals.

An automatic apparatus for the continuous measurement of O2 consumption of small laboratory animals is described. By use of a high-sensitivity pressure transducer with associated circuitry together with a peristaltic O2 delivery system, the closed respirometer chamber is maintained at atmospheric pressure +/- 0.5 mmH2O. O2 delivery is measured to within 0.25 ml by recording rotations of the peristaltic pump, following calibration by the withdrawal of a preset volume of air from the chamber. Static trials (with the chamber empty) indicate a high degree of reproducibility of data with the chamber pressure remaining at atmospheric pressure +/- 0.5 mmH2O as a result of the proportional, as opposed to fixed-volume, delivery of O2. Trials with mice and rats have likewise produced data with a high degree of reproducibility.

Animals↗
PubMed1980

Insulin secretion by the perfused pancreas of the cold-acclimated rat.

Rats were acclimated to cold at 4 degrees C for a period of 42 days. Pancreases of normal and cold-acclimated rats were isolated and perfused with a Krebs-Henseleit bicarbonate medium containing dextran, adenosine, glucose, and a fluorocarbon as oxygen carrier. The biphasic secretion pattern of insulin in response to glucose stimulation was evident in both groups. Both basal and glucose-induced insulin release from pancreases of cold-acclimated rats exhibited a very significant reduction in comparison with controls (p less than 0.001). These observations are interpreted as indicating that cold-acclimation, an altered steady state of metabolism, is characterized by enhanced sympathetic activity which reduces insulin availability and release. Consequently enhanced free fatty acid mobilization resulting from reduced inhibition by insulin of lipolysis in the peripheral fat depots and increased lipolysis resulting from sympathetic activation are seen.

Acclimatization↗