SUMMARY1. The extent to which the splanchnic sympathetic innervation is implicated in the control of plasma glucagon concentration has been investigated in the young calf.2. Stimulation of the peripheral ends of both splanchnic nerves (0.5-10.0 c/s for 10 min) caused an abrupt increase in plasma glucagon concentration in adrenalectomized calves 3-5 weeks after birth. This effect was found to be statistically significant (P < 0-01) at each of these frequencies. In calves tested during the first 24 hr after birth comparatively small responses were obtained.3. The hyperglyeaemia produced by splanchnic nerve stimulation in older calves caused an abrupt rise in plasma insulin concentration when stimulation was discontinued but insulin release was completely inhibited throughout the period of stimulation at all frequencies tested.4. It is concluded that tonic changes in sympathetic efferent activity are likely to modify plasma glucagon concentration in the normal conscious calf.
SUMMARY1. The extent to which the autonomic innervation to the pancreas is implicated in the control of glucagon release during hypoglycaemia has been investigated in calves 3-6 weeks after birth.2. A pronounced rise in plasma glucagon concentration occurred in normal conscious calves in response to hypoglycaemia following administration of insulin (0.1 u./kg). Prior treatment with atropine caused no significant change in the hypoglycaemic response to insulin in these animals but the rise in plasma glucagon concentration was delayed.3. Section of both splanchnic nerves produced no significant change in the tolerance of conscious calves to this small dose of insulin and the changes in plasma glucagon concentration in these animals were within the normal range. 4. In contrast, the same dose of insulin produced severe hypoglyeaemia, accompanied by convulsions, in atropinized calves with cut splanchnic nerves. In spite of the intensity of the hypoglycaemic stimulus the rise in plasma glucagon concentration was both delayed and diminished in these animals.5. Administration of atropine alone (0-2 mg/kg) to normal fasting calves produced a significant fall in the mean plasma concentrations of both glucose and glucagon (P < 0-01) within 30 min, without affecting that of insulin.6. A significant increase in plasma glucagon concentration also occurred in response to stimulation of the peripheral ends of the thoracic vagi in adrenalectomized calves with cut splanchnic nerves under barbiturate anaesthesia. A rise in mean plasma glucose concentration was also observed in these experiments and found to be significantly correlated with the glucagon response. 612 S. R. BLOOM, A. V. EDWARDS AND N. J. A. VAUGHAN 7. It is concluded that changes in either sympathetic or parasympathetic efferent activity may modify plasma glucagon concentration in the conscious calf, but that only the latter mechanism is likely to be implicated in the response to changes in plasma glucose concentration within the physiological range.
Severe pituitary Cushing's disease of sudden onset after 18 years of unsuccessful treatment for a previously non-functioning chromophobe adenoma is described in a middle-aged woman. Initial presentation with symptoms of optic nerve compression had been preceded by two years of amenorrhoea. Transfrontal resection of a chromophobe adenoma followed by radiotherapy, performed both at this time and again after a recurrence eight years later, failed to eradicate the tumour. Ten more years elapsed before she rapidly developed florid features of Cushing's syndrome. Plasma ACTH levels were markedly elevated and were only partially reduced by further transfrontal surgery, complete removal of the tumour proving impossible. Subsequent bilateral adrenalectomy was performed to control her hypercortisolism and a course of cytotoxic chemotherapy was administered in an attempt to treat the tumour recurrence. Immunocytochemical staining of tumour obtained at surgery demonstrated ACTH immunoreactivity both before and after the development of Cushing's disease. Although silent corticotrophic adenomas of the human pituitary, including chromophobic tumours, have been previously described, this is the first report of such a tumour becoming functional, sufficient to cause clinically evident Cushing's disease.
Summary. Insulin withdrawal studies were performed in 12Type1 (insulin-dependent) C-peptide negative diabetic patients with low to moderate insulin antibody levels, to assess the biological availability of antibody-bound insulin and its clinical significance. There was a highly significant correlation between the extent to which the free insulin concentration was maintained during the period of insulin withdrawal and both the level of insulin-binding by serum and the total insulin concentration at the start of the study. During insulin withdrawal, the patients who best maintained their circulating free insulin levels showed the smallest increases in blood glucose and 3-hydroxybutyrate concentrations. We conclude that antibody-bound insulin is available for physiological action, and that in those individuals with moderate antibody concentrations it is capable, in the fasting state, of maintaining free insulin levels. In these circumstances insulin antibodies are behaving as simple carrier proteins.Key words: Type 1 diabetes, insulin, insulin antibody, pharmacokinetics.Most clinical studies concerning insulin antibodies have been directed towards the deleterious effects, such as insulin resistance, which are associated with very high antibody levels [1]. Little is known about the effect of the more modest levels of antibodies that exist in most Type 1 (insulin-dependent) diabetic patients. In these patients, it is evident from measurement of antibody-bound insulin that substantial quantities of insulin may be present in the plasma and it has been suggested that this source of insulin could act as a buffer to fluctuations in insulin levels [2].A correlation between the level of insulin binding by serum and diabetic control as judged by the haemoglobin A1 percentage has been demonstrated in C-peptide negative patients on a once-daily insulin regimen [3], but this association was not observed when the patients were changed to a twice-daily insulin regimen. The problem of whether antibody-bound insulin is available for biological action, and the extent to which it might be clinically useful, is of particular interest because over recent years there has been a reduction in both the prevalence of insulin antibodies and the insulin-binding levels found in those who do form antibodies. This is a consequence of the increased purity of insulin preparations and the increase in the use of porcine insulin. To assess the availability of insulin from the antibodybound pool, we performed studies on Type 1 diabetic patients who had low to moderate serum insulin binding and no residual C-peptide secretion. After careful depletion of subcutaneous insulin, subjects were stabilised on intravenous insulin which was then discontinued. The only source of free insulin would then be from the pool of insulin bound to antibody. The concentrations of free and total insulin in serum and of glucose and 3-hydroxybutyrate in blood were measured to assess the bioavailability of this source of insulin. Subjects and Methods SubjectsThe twelve Type 1...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.