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Biomedical subjects

R G Clark

Publications and source records attributed to R G Clark.

187 records · Page 11Linked to original sources

A simple computer model for insulin-receptor interactions and insulin dependent glucose uptake by adipocytes.

A simple computer model is described for the simulation of insulin binding to cell surface receptors on adipocytes and the subsequent stimulation of glucose uptake. The model is based on the currently accepted physiology and biochemistry of insulin action. The model successfully simulated changes in sensitivity to insulin with changes in receptor numbers seen with in vitro experiments; it is also consistent with the proposal that an increased rate of insulin-receptor complex internalisation should lead to an insulin-resistant state. The model also suggests that such an insulin-resistant state should not be affected by a subsequent increase in the rate of return of internalised receptors to the outer cell surface.

Adipose Tissue↗

Growth induced by pulsatile infusion of an amidated fragment of human growth hormone releasing factor in normal and GHRF-deficient rats.

The discovery of human pancreatic growth hormone releasing factors (GHRFs) and subsequent characterization of human hypothalamic GHRF has led to studies on the role of these peptides in stimulating growth hormone (GH) release, and attempts to use GHRF peptides to increase growth rates in short children are already underway. However, there is no experimental evidence in animals that exogenous GHRF promotes growth in vivo. Although anaesthetized rats release GH reproducibly in response to GHRF injections, the responses in conscious male rats are much more variable, perhaps because of their highly episodic endogenous GH secretory pattern. In contrast, female rats secrete GH in a more continuous pattern and respond reproducibly to repeated injections of GHRF. We report here that it is possible to establish a 'male' type of GH secretory pattern in normal female rats by long-term pulsatile intravenous (i.v.) infusions of the active human GHRF fragment GHRF (1-29)NH2. We found that this treatment accelerates growth and increases pituitary GH content, whereas continuous infusions of this GHRF fragment at the same daily dose are ineffective. Pulsatile, but not continuous GHRF also stimulates growth in animals made GHRF-deficient by neonatal monosodium glutamate treatment. Thus exogenous GHRF will stimulate growth in both GHRF-deficient and normal animals provided it is administered in an appropriate pattern.

Animals↗

A proposed new approach and protocol to defining mineral deficiencies using reference curves. Cobalt deficiency in young sheep is used as a model.

The most conclusive way of determining whether animals are deficient in a trace element is to measure production responses to supplementation in a field trial. However the opportunity, expertise and resources necessary to run such trials are not always readily available and there is often a considerable delay in reaching a diagnosis. Provided the degree of a production response can be closely related to a tissue level of the element or its metabolite then analysis of tissue samples can replace the need for field trials. The paper uses data from a series of cobalt liveweight response trials with lambs to outline a proposed methodology for constructing response curves which, for any specified level of Vitamin B12 in serum, can be used to determine (a) the expected liveweight response to supplementation, and (b) the probability of getting a response at least as great as some given level eg. that considered sufficient to just cover the costs of rectifying the deficiency. A protocol for future production response trials is described. It is planned that all appropriate production response trial data will be used to derive ;response; and ;probability of response; curves for use in diagnosing cobalt, selenium and copper deficiencies in sheep and cattle. It is suggested that the methodology could be applied in many biological systems involving deficiencies.

Journal Article↗