Iatrogenic hyperinsulinism at birth.
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Female↗
Biomedical subjects
S R Bloom
Publications and source records attributed to S R Bloom.
Neural and humoral factors in postoperative ileus.
Two inhibitory mechanisms in the human colon which may contribute to postoperative ileus have been studied. Dopamine, a possible peripheral neurotransmitter, inhibited isolated colonic smooth muscle strips by a direct effect in longitudinal muscle any by a nerve-mediated mechanism as circular muscle. Plasma motilin levels were suppressed pre- and per- operatively and elevation of levels postoperatively correlated with the return of normal motility and the severity of the operation.
Cholecystectomy↗
Improved glucose tolerance four hours after taking guar with glucose.
To gain some insights about the possible cumulative metabolic effect after a high-fibre meal, 6 subjects took two 80 g oral glucose loads, 4 h apart. Addition of 22.3 g guar to the first load decreased the rise in blood glucose and insulin after the second (guar-free) load by 50% (p less than 0.002) and 31% (p less than 0.02) respectively. This corresponded with decreased 3-hydroxybutyrate levels at the start of the glucose tolerance test after guar (by 20%, p less than 0.02). When no guar was added to the first glucose load, both 3-hydroxybutyrate and non-esterified fatty acids tended to rise before the second test. No significant effect was seen in the responses of the gut hormones, gastric inhibitory peptide and enteroglucagon. Spreading the intake of the first 80 g of glucose over the initial 4 h (2 subjects) similarly flattened the glycaemic but increased the insulin response. The effect of guar on carbohydrate and fat metabolism, therefore, lasts at least 4 h and may result in improved carbohydrate tolerance to subsequent guar-free meals.
Adult↗
VIP in the rat brain: evidence for a major pathway linking the amygdala and hypothalamus via the stria terminalis.
We report here on the detailed distribution of VIP-like immunoreactivity in the rat brain by a combined immunological approach using immunocytochemistry and radioimmunoassay. VIP-like immunoreactivity was widely distributed. Cell bodies and and fibres were noted principally in the cortex, hippocampus, amygdala, suprachiasmatic nucleus and brain stem. In addition dense areas of immunoreactive fibres and terminals were seen in the stria terminalis and its bed nucleus. The fibres appear to form a major VIP-containing pathway which links the amygdaloid complex with the hypothalamus. Although the functional significance of VIP in the brain is unknown, its presence in the amygdala, the hypothalamus and their linking pathway, as well as its pharmacological actions suggest that it may play a role in neuroendocrine regulation and the modulation of hypothalamic function.
Amygdala↗
The differential distribution of vasoactive intestinal polypeptide in the normal human female genital tract.
VIP-like immunoreactive material is present in the female reproductive tract, with a distinct pattern of distribution. The highest concentrations of extractable material and immunoreactive nerve fibres were found in the cervix and vagina. In the cervix these fibres were seen below the surface epithelium and around cervical glands as well as in association with blood vessels and smooth muscle bundles. In the vagina the nerve fibres were most abundant in th superficial regions of the lamina propria. Scattered fibres were also present in the rest of the uterus and in the fallopian tubes. Chromatographic evidence indicates that this VIP-like material is of a similar molecular size to that extracted from other organs. Possible roles for VIP in the regulation of myometrial activity and of cervical and vaginal dilation and secretion are proposed.
Adult↗
The location of VIP in the pancreas of man and rat.
VIP has powerful stimulatory effects on both endocrine and exocrine pancreas but its localisation within the gland has not been established. In this study, human pancreas was obtained fresh at surgery (eleven) or within four hours of death (seven). The pancreas was also removed from rats (twenty-two). Immunocytochemical staining showed VIP to be present in fine nerve fibres in all areas of the pancreas. Many fibres were seen in the exocrine pancreas, running between the acini, and around ducts and blood vessels. In addition, dense networks of fibres were observed forming meshes around islets and occasional ganglia were found containing immunoreactive cell bodies. In general, there were fewer VIP fibres in the rat pancreas than in the human, but overall distribution was identical. The mean VIP content of whole human pancreatic tissue was 42 +/- 10 pmol/g wet weight (38 +/- 9 pmol/g in head, 49 +/- 6 pmol/g in body and 42 +/- 11 pmol/g in tail). Whole rat pancreatic tissue contained 28 +/- 7 pmol/g wet weight while preparations of isolated islets were found to contain 374 +/- 30 pmol/g. It is possible that the heavy VIP innervation of the islets described here indicates a role in the regulation of islet hormone release.
Animals↗
Beta blockade and diabetes mellitus: effect of oxprenolol and metoprolol on the metabolic, cardiovascular, and hormonal response to insulin-induced hypoglycemia in normal subjects.
In a double-blind randomized study, the effect of the acute administration of a single oral dose of oxprenolol, a nonselective beta-blocker, and of metoprolol, a beta 1 selective blocker, on insulin-induced hypoglycemia was tested in seven normal subjects. Neither of the drugs potentiated the hypoglycemic effect of insulin. The recovery from hypoglycemia was delayed by both blocking agents only in the late phases of the experimental observation. This effect could not be accounted for by suppression of release of the counterregulatory hormones glucagon or cortisol, but may be mediated by the inhibition of NEFA and gluconeogenic-substrate release in response to hypoglycemia. Both drugs blocked the hypoglycemia-induced tachycardia. Only oxprenolol raised diastolic blood pressure during hypoglycemia. Symptoms of hypoglycemia were not masked by either blocking agent, and sweating was enhanced and prolonged by both drugs. Thus, no clear-cut differences in the glycemic response to insulin-induced hypoglycemia were found between metoprolol and oxprenolol, but the drugs differed in their influence upon the blood pressure response to insulin-induced hypoglycemia.
Adrenergic beta-Antagonists↗
Beta blockade and diabetes mellitus: effect of oxprenolol and metoprolol on the metabolic, cardiovascular, and hormonal response to insulin-induced hypoglycemia in insulin-dependent diabetics.
The effect of the administration of a single oral dose of placebo, oxprenolol and metoprolol on insulin-induced hypoglycemia was investigated in seven insulin-dependent diabetics in a double-blind randomized study. Neither of the beta-blocking agents accelerated the plasma glucose lowering effect of insulin. Plasma glucose recovery from hypoglycemia was grossly impaired in diabetics whether blocked or not, and all investigations had to be terminated by i.v. glucose injection after 1 hr of sustained hypoglycemia. During the period of observation, no further delaying effect by either beta-blocker was observed. The lack of plasma glucose recovery seems to be at least in part related to a retarded and reduced glucagon response to hypoglycemia. Both drugs blocked the hypoglycemia-induced pulse rate increase, but neither caused bradycardia. A significant increase in diastolic pressure was recorded with oxprenolol, whereas a drop in systolic pressure was noted with metoprolol. Oxprenolol suppressed the NEFA rise after insulin-infusion termination to a greater extent than did metoprolol. Hypoglycemic symptoms were not affected by beta-blockade. The results suggest that neither drug further worsens the already grossly impaired plasma glucose recovery, but that oxprenolol and metoprolol may differ in their effects on hemodynamic response to hypoglycemia. This aspect of the problem requires further study under careful control in hypertensive diabetics.
Adrenergic beta-Antagonists↗
Hormonal and metabolic rhythms in Cushing's syndrome.
Hormone and metabolite profiles were investigated over a 12-hr period in six patients with Cushing's syndrome, ten age- and sex-matched normal controls, and six moderately obese subjects matched for weight with the patient group. Mean diurnal plasma cortisol levels were 563 +/- 74 nmole/liter in the patients, 275 +/- 22 nmole/liter in normal controls and 241 +/- 32 nmole/liter in obese subjects, with total loss of diurnal changes in Cushing's syndrome. Fasting blood glucose concentration was similar in all groups although mild hyperglycemia occurred after meals in the Cushing's patients compared with normal and obese subjects (mean 12-hr blood glucose: Cushing's 6.31 +/- 0.39 mmole/liter; normal controls, 5.32 +/- 0.14 mmole/liter, p < 0.01; obese subjects, 5.41 +/- 0.18 mmole/liter, p < 0.05) despite marked hyperinsulinemia (mean 12-hr serum insulin: Cushing's 57.3 +/- 18.2 mU/liter; normal controls, 19.7 +/- 2.5 mU/liter, p < 0.02; obese subjects, 18.1 +/- 4.0 mU/liter, p < 0.05). Concentrations of the gluconeogenic precursors lactate, pyruvate, and alanine were raised in Cushing's syndrome, particularly postprandially. Plasma nonesterified fatty acids (NEFA), blood glycerol, and blood ketone body concentrations were comparable in all three groups although the normal diurnal variation in circulating NEFA and ketone body levels was lost in Cushing's syndrome. Serum triglyceride (TG) concentrations were grossly elevated in the Cushing's patients (mean 12-hr serum TG: Cushing's 3.51 +/- 1.23 mmole/liter; normal controls 0.89 +/- 0.19 mmole/liter, p < 0.02; obese subjects, 0.93 +/- 0.23 mmole/liter, p < 0.05) and correlated positively with serum insulin levels. Plasma glucagon concentrations were raised in Cushing's syndrome (mean 12-hr plasma glucagon: Cushing's 23.2 +/- 3.7 pmole/liter; normal controls 12.3 +/- 1.5 pmole/liter p < 0.01; obese subjects 12.2 +/0 2.0 pmole/liter, p < 0.02) and correlated positively with the serum cortisol but not with blood alanine, suggesting that some stimulatory factor other than alanine was responsible. The metabolic effects of chronic glucocorticoid excess thus may not be explained on the basis of obesity alone. Compensatory hyperinsulinemia limits the disturbance of carbohydrate and lipid metabolism in Cushing's syndrome but may be important in production of the hypertriglyceridemia observed.
Adolescent↗
Immunohistochemical studies of the enteric nervous system in tissue culture and in situ: localization of vascoactive intestinal polypeptide (VIP), substance-P and enkephalin immunoreactive nerves in the guinea-pig gut.
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Animals↗
The effects of anabolic steroids on growth, body composition, and metabolism in boys with chronic renal failure on regular hemodialysis.
Eight boys aged 9.5 to 17 years, on regular hemodialysis for chronic renal failure, were treated for 0.4 to 1.3 years with the anabolic steroid oxandrolone. The effects on linear growth, skeletal maturation, cell mass, and the fasting levels and response to intravenous glucose of BG, IRI, NEFA, BCAA, and IRG were measured. Following treatment there was a significant increase in mean growth velocity, growth velocity standard deviation score related to bone age, and cell mass. Overall skeletal maturation was not accelerated, and only a small advance in pubertal status was seen. There was a decrease in fasting levels of BG and NEFA; fasting BCAA and IRG were increased. The response to intravenous glucose was altered; there was a decrease in peak BG response, an increase in peak IRI response, and a more marked fall in plasma NEFA and BCAA levels. Fasting IRG levels correlated with fasting BG levels, and fell significantly following intravenous glucose both before and after treatment. Hepatotoxicity, which was reversible, was seen in a ninth boy who did not complete the study. The only other side effect, salt and water retention, was controlled by a reduction in oxandrolone dosage. These preliminary results suggest that anabolic steroids may be useful to stimulate anabolism and growth in uremic children, and that their effect is mediated by an increase in insulin secretion and/or an improvement in tissue sensitivity to insulin. Further studies with careful monitoring are required to substantiate the effect on final height and the risks involved.
Adolescent↗
Glucagonomas, VIPomas and somatostatinomas.
The three new endocrine pancreatic tumour syndromes dealt with in this chapter--glucagonomas, VIPomas and somatostatinomas--are not common. Nonetheless, the patients are potentially curable by tumour resection and therefore wider knowledge of the clinical picture is of considerable importance. It is possible that there are still further, presently unrecognized, clinical syndromes waiting in the wings and studies are currently under way to try to ascertain the effects of elevated PP. Early tumour diagnosis depends firstly on clinical acumen but the easy availability of a reliable radioimmunoassay service is of considerable importance as this allows the physician to screen likely patients and so detect cases at an early stage. Tumour localization is still a major problem and requires expert radiological assistance. The dramatic effectiveness of the cytotoxic agent streptozotocin illustrates the great potential of chemotherapy and it may be expected that further drugs of this nature will be discovered, especially as it is now possible to establish isolated tumour strains for mass drug screening. These tumours have shown the effect of long continued peptide elevation and given valuable insight into the physiological role of the respective regulatory peptides.
Adenoma, Islet Cell↗
Physiology of gastrointestinal hormones.
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Animals↗
The diffuse neuroendocrine system in gastroenterology.
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Animals↗
Subcellular fractionation studies of human gastric antrum: localization of the mucosal peptide hormones.
1. Analytical subcellular fractionation techniques have been applied to endoscopic human gastric antral biopsies to study the localization of gastrin, somatostatin, vasoactive intestinal peptide and the properties of the principal subcellular organelles. 2. The peptide hormones, detected by radioimmunoassay, showed particulate localizations with single peaks in the density gradients for somatostatin (modal density 1.23) and vasoactive intestinal peptide (modal density 1.17). Gastrin showed a more complex distribution with a distinct peak (modal density 1.18) and a substantial shoulder extending into the denser regions of the gradient. 3. The following organelles, characterized by their marker enzymes, were located in the density gradients: plasma membrane (5'-nucleotidase), mitochondria (malate dehydrogenase), peroxisomes (catalase), lysosomes (beta-N-acetyl-D-glucosaminidase), endoplasmic reticulum (neutral alpha-aminidase), cytosol (lactate dehydrogenase). 4. This technique can be applied to investigate disease of the gastric antrum at a subcellular level.
Acetylglucosaminidase↗
Elevation of plasma neurotensin in the dumping syndrome.
1. The pathophysiology of the dumping syndrome is poorly understood. Plasma levels of four small intestinal hormones have been measured after an oral glucose provocation test in 19 patients with dumping symptoms and in matched controls. 2. Plasma levels of neurotensin, a newly discovered highly potent, hypotensive ileal peptide, were significantly increased in symptomatic patients compared with those of controls [20 min rise of 43 +/- 6.0 (mean +/- SEM) pmol/l in 19 symptomatic patients, 8.0 +/- 5.5 pmol/l in 20 postoperative symptom-free patients, and 4.1 +/- 3.5 pmol/l in 20 pre-operative patients with duodenal ulcer, P < 0.01]. 3. The rise in enteroglucagon was greater than normal but of similar magnitude to that seen in several other gastrointestinal conditions not associated with dumping symptoms. 4. The release of both gastric inhibitory peptide and motilin did not differ significantly from that of controls.
Blood Glucose↗
Subcellular fractionation studies of human rectal mucosa: localization of the mucosal peptide hormones.
1. Analytical subcellular fractionation techniques have been applied to endoscopic human rectal biopsies to study the localization of enteroglucagon, somatostatin, vasoactive intestinal peptide and the properties of the principal subcellular organelles. 2. The peptide hormones, detected by radioimmunoassay, showed particulate localizations with single peaks in the density gradients for enteroglucagon (modal density 1.25) and somatostatin (modal density 1.23). Vasoactive intestinal peptide showed a less discrete localization but demonstrated a major peak (modal density, 1.17) with a small subsidiary peak (modal density 1.24). 3. The following organelles, characterized by their marker enzymes, were located in the density gradients; plasma membrane (5'-nucleotidase), mitochondria (malate dehydrogenase), peroxisomes (catalase), lysosomes (beta-N-acetyl-D-glucosaminidase), endoplasmic reticulum (neutral alpha-D-glucosidase) and cytosol (lactate dehydrogenase). 4. This technique can be used to investigate disease of the human rectum at a subcellular level.
Centrifugation, Isopycnic↗