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Biomedical subjects

V Marks

Publications and source records attributed to V Marks.

387 records · Page 22Linked to original sources
PubMedDate not supplied

Effect of glucagon on carbohydrate-mediated secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1).

BACKGROUND: The insulinotropic hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1), regulate insulin secretion to nutrient intake and constitute the endocrine arm of the entero-insular axis. Glucagon has been implicated in the pathophysiology of conditions characterised by abnormal glucose tolerance such as obesity and diabetes mellitus although its effect on the entero-insular axis is not fully understood. Materials and methods We investigated the effect of exogenous glucagon on the entero-insular axis and its relation to gastric emptying in six healthy men aged [mean (+/-S.E.M. )] 23.6 (0.9) years with a body mass index of 24.0 (1.5) kg/m(2). Plasma glucose, GIP, GLP-1, insulin and paracetamol concentrations were measured before and after a 100 g oral carhohydrate load containing 1.5 g of paracetamol for 6 h during intravenous infusion of either glucagon or saline. RESULTS: When compared to the saline infusion, peak and integrated insulin and glucose concentrations were higher (p<0.05) following glucagon infusion. After 60 min paracetamol concentrations were lower (p<0.05) following glucagon infusion. Integrated responses for GIP and GLP-1 were markedly reduced following glucagon infusion. CONCLUSIONS: Exogenous glucagon in addition to its well-documented action of increasing glucose and insulin concentrations and delaying gastric emptying also markedly reduces GIP and GLP-1 secretion. The inhibition of GLP-1 soon after commencement of glucagon infusion supports a direct effect of glucagon on intestinal L-cells. We speculate that the marked inhibition of postprandial GLP-1 secretion by glucagon may be of importance in the pathogenesis of relative insulinopenia in Type 2 diabetes and in the development of reduced satiety in obesity and diabetes.

Acetaminophen↗
PubMedDate not supplied

A propranolol radioimmunoassay and its use in the study of its pharmacokinetics following low doses.

A radioimmunoassay has been developed for propranolol with a sensitivity of 2.37 nmol l-1 in unextracted plasma using a 50 microliter sample. Plasma concentration measurements were made on samples from volunteers for up to 8 h after they had been given 5, 10, or 40 mg of propranolol by mouth. Analysis of the results showed that mean elimination half-lives and total body clearances were similar following each of the doses and that the area under the curve was proportional to the dose. Steady-state propranolol concentrations in 17 patients on regular propranolol treatment were linearly related to the dose ver the range 20-640 mg d-1; the regression line extrapolated to the origin. These data indicate non-saturable kinetics for the hepatic metabolism of propranolol within the dose ranges investigated and lead us to believe that there is no 'oral-threshold' dose for propranolol. The radioimmunoassay may be useful in clinical practice for monitoring plasma propranolol concentrations and for detecting patient compliance.

Adult↗
PubMedDate not supplied

Physiologic observations in a controlled clinical trial of the antiemetic effectiveness of 5, 10, and 15 mg of delta 9-tetrahydrocannabinol in cancer chemotherapy. Ophthalmologic implications.

One hundred twenty patients about to receive their first treatment with potentially nauseant cancer chemotherapy were randomized to one of six antiemetic treatments: (1) no treatment; (2) placebo; (3) prochlorperazine (PCPZ), 10 mg; (4) delta 9-tetrahydrocannabinol (THC), 5 mg; (5) THC, 10 mg; (6) THC, 15 mg. Four doses of each medication were given orally at 4-hour intervals starting 2 hours before chemotherapy. A study nurse was responsible for both objective (nurse) and subjective (patient) symptom questionnaires. Serum levels were obtained at intervals for cross-reacting cannabinoids. Physiologic measurements including intraocular pressure (IOP), blood pressure, and pulmonary function were also recorded. In summary, the patients were remarkably free of adverse physiologic effects. All intraocular pressures before and after treatment were within the normal range, although a surprising statistically significant increase in IOP occurred in the group receiving 5 mg THC.

Antineoplastic Agents↗
PubMedDate not supplied

Reversal of diabetes by syngeneic transplantation of a radiation-induced rat insulinoma.

The growth and metabolic effects of a radiation-induced rat insulinoma were examined after subcutaneous subscapular transplantation into normal and streptozotocin diabetic NEDH rats. Streptozotocin diabetic rats exhibited hyperglycaemia, hypoinsulinaemia, impaired glucose tolerance without an insulin response, polyuria, polydipsia, hyperphagia and weight loss. Transplantation of tumour fragments gradually improved the physical and metabolic state over the following 3 weeks. Coincident with a progressive rise in plasma insulin between 10 and 17 days, the diabetic rats gained weight and reduced their food intake. The rats remained hyperglycaemic during this time, but developed hypoglycaemia with marked hyperinsulinaemia by 24 days. Furthermore, plasma glucose and insulin concentrations were not increased by an intraperitoneal glucose challenge, indicating greatly accelerated glucose clearance. Both the streptozotocin-treated and normal insulinoma-bearing rats incurred a fatal hypoglycaemic coma by 28-33 days after transplantation. Final body weights, tumour weights and concentrations of glucose and insulin were similar in the two groups. This study demonstrates reversal of streptozotocin diabetes by insulinoma transplantation. The hyperglycaemia and the accompanying diabetic environment did not modify tumour growth and development.

Adenoma, Islet Cell↗
PubMedDate not supplied

Visual function during acute hypoglycaemia.

Hypoglycaemia symptoms are of particular interest in view of the importance of hypoglycaemia unawareness. Visual symptoms arising during acute hypoglycaemia may be the result of metabolic disturbances in the visual pathways within the central nervous system or impairment of the refractive apparatus of the eye and binocular function. This study investigated the effect of hypoglycaemia upon visual acuity, binocular interaction and contrast sensitivity. Various aspects of visual function were examined in ten normal subjects before, during and after acute insulin-induced hypoglycaemia. A simultaneous study of hypoglycaemic symptoms enabled us to relate the objective findings to the symptoms as reported by the subjects. Snellen visual acuity, fusion and stereopsis were not affected by hypoglycaemia. Five subjects noted visual disturbance. Eight developed significant impairment of contrast sensitivity, which closely matched the lowered blood glucose concentration. These observations suggest that hypoglycaemic visual symptoms are due to neuroglycopenia of central visual pathways rather than changes within the refractive apparatus or abnormality of binocular function. Although these symptoms are not a constant feature of the hypoglycaemic state, subtle impairment of visual function occurs in most cases. Contrast sensitivity testing can be useful for assessment of fine changes in visual function.

Accommodation, Ocular↗
PubMedDate not supplied

Effects of diet-induced ketosis in rats with hypoglycaemia due to a serially transplantable insulinoma.

In view of the ability of ketones to partially replace glucose as an alternative fuel in the brain, the potential protective effects of diet-induced ketosis were examined in male NEDH rats with hypoglycaemia due to a serially transplantable radiation-induced insulinoma. Ketosis was induced by daily oral administration of medium chain triglycerides to normal rats and to insulinoma-bearing rats 1 day after subcutaneous subscapular implantation of tumours fragments. All rats treated with medium chain triglycerides became ketotic within 72 hours, and plasma 3-hydroxybutyrate concentrations remained 5-10 fold elevated at 24 days. Untreated insulinoma-bearing rats became moderately hyperinsuliaemic and hypoglycaemic by 17 days, with the later manifestation of more marked hyperinsulineamia (21.6 +/- 0.8 ng/ml, mean +/- SEM) severe hypoglycaemia (1.5 +/- 0.1 mmol/l) and death by 24-28 (26 +/- 1) days. Induction and maintenance of hyperketonaemia did not affect the development of hyperinsulineamia, hypoglycaemia or the exaggerated fall of plasma glucose produced by an 8 hour fast in these rats. However by day 21, the severity of hypoglycaemia was greater in insulinoma-bearing rats receiving medium chain triglycerides, culminating in accelerated death by 22-25 (23 +/- 1) days and an accompanying 50% decrease in final tumour weight. These results demonstrate that induction of ketosis in the face of marked hyperinsulinaemia did not afford protection against the profound hypoglycaemia produced by a serially transplantable rat insulinoma.

3-Hydroxybutyric Acid↗