Diabetes and the gastro-intestinal tract.
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Diabetes Complications↗
Biomedical subjects
R G Long
Publications and source records attributed to R G Long.
Hepatitis B protection of endoscopy staff.
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Endoscopy↗
Stimulation by 1,25-dihydroxyvitamin D3 of adenylate cyclase along the villus of chick duodenum.
Administration of 650 pmol 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] to vitamin D-deficient chicks increased adenylate cyclase activity in the basolateral membrane of duodenal epithelial cells within 24 h. This increase in enzymatic activity was accompanied by an increase in calmodulin content of the basolateral membrane. Although neither exogenously added calmodulin (up to 10 micrograms/ml) nor calcium (from 10(-7)-10(-5) M) stimulated enzyme activity, calmodulin antagonists trifluoperazine, W7, and W13 inhibited it. When calmodulin content, adenylate cyclase activity, and alkaline phosphatase activity were measured in cells sequentially eluted from the tip to the base of the villus, cells from the midregion and base had the highest calmodulin content and adenylate cyclase activity, whereas alkaline phosphatase activity (a brush border membrane enzyme) was highest in cells eluted from the tip. Adenylate cyclase activity was increased by 1,25-(OH)2D3, particularly in cells from the midvillus. Our results indicate that the response of adenylate cyclase activity to 1,25-(OH)2D3 varies along the villus and suggest that calmodulin may be involved.
Adenylyl Cyclases↗
Somatostatin and the dumping syndrome.
Infusion of somatostatin reduced the symptoms of the early dumping syndrome after oral glucose was given and also reduced the associated tachycardia and rise in packed cell volume. It inhibited the secretion of enteroglucagon, neurotensin, and vasoactive intestinal polypeptide, which are raised in patients with the dumping syndrome and may have an aetiological role. It also prevented the reactive hypoglycaemia of late dumping by inhibiting the release of gastric inhibitory polypeptide and insulin. Somatostatin, possibly through its inhibitory effects on hormonal secretion, may have a role in the management of patients with the early and late dumping syndrome.
Blood Glucose↗
Plasma peptide YY (PYY) in dumping syndrome.
The newly isolated hormonal peptide PYY is mainly localized to endocrine cells of the lower intestinal mucosa. The release of PYY by oral glucose was studied in six patients with the dumping syndrome to ascertain the effect of this condition on PYY release. Plasma PYY concentrations were greatly increased following oral glucose in patients with the dumping syndrome compared with healthy controls. In a separate series of experiments, the effect of somatostatin infusion on the PYY release by glucose in these patients was investigated. The release of PYY was completely blocked by infusion of somatostatin, and its release from the bowel in normal subjects may therefore be modulated by local somatostatin in the gut. PYY has been shown to inhibit gastric acid secretion and emptying, at plasma concentrations similar to those seen after glucose, in patients with the dumping syndrome. PYY may therefore be a factor involved in the pathophysiological changes associated with this condition.
Chromatography, Gel↗
Somatostatin-14 modulates postprandial glucose levels and release of gastrointestinal and pancreatic hormones.
Ingestion of a 4,500-kcal mixed meal by healthy volunteers resulted in a significant rise of plasma somatostatin-14-like immunoreactivity (9 +/- 1 pmol l-1. Whether this peptide has a role as a humoral agent or not is still controversial and, until recently, most studies investigating its effects by exogenous administration have produced vastly supraphysiological circulating plasma levels. In order to reproduce the rise obtained following the large meal, synthetic somatostatin-14 was infused at a dose of 0.8 pmol kg-1 min-1 before and during a 530-kcal test breakfast. This resulted in a rise of 8 + 2 pmol l-1 in the peripheral circulation. This infusion produced a significant reduction in the postprandial release of insulin, gastric inhibitory polypeptide, pancreatic polypeptide and in the preprandial motilin levels. In contrast, blood glucose levels following the breakfast were elevated when compared to the control saline infusion. This suggests that somatostatin possesses true endocrine functions and is capable of profoundly altering the postprandial glucose and hormone response.
Adult↗
Genetic and phenotypic relationships among type traits scored linearly in Holsteins.
Phenotypic and genetic parameters were estimated for 12 type traits of Holstein cows scored linearly by personnel of an artificial insemination organization. Estimates were compared with those from programs offered by the breed association and by two other artificial insemination organizations. All programs were based on scoring guidelines of the National Association of Animal Breeders. Heritabilities of linear type traits ranged from .40 for stature to .14 for fore udder attachment with heritabilities for udder traits smaller than for nonudder traits. Largest genetic and phenotypic correlations were among udder traits with genetic correlations consistently exceeding phenotypic correlations. Similarities in relative magnitudes of phenotypic and genetic parameters suggest that linear type appraisal programs do not differ greatly among organizations using scoring guidelines of the National Association of Animal Breeders.
Animals↗
Vasoactive intestinal polypeptide-secreting tumours (vipomas) in childhood.
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Adenoma, Islet Cell↗
Recent advances in pancreatic hormone research.
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Diabetes Mellitus↗
Effects of intravenous somatostatin and motilin on the blood glucose and hormonal response to oral glucose.
Exogenous intravenous infusions of control saline, somatostatin, motilin and somatostatin and motilin together were compared in normal volunteers for their effects on the rise of blood glucose following 50 g oral glucose and for their effects on gastric emptying and plasma hormone concentrations. All regulatory peptide infusions increased the rate of gastric emptying by between 182% and 198% at 60 min post-ingestion. The glucose response during the oral glucose tolerance test was suppressed when somatostatin with or without motilin was infused but was increased during motilin. The somatostatin infusion reduced concentrations of motilin, insulin, gastric inhibitory polypeptide, gastrin and neurotensin whilst the motilin infusion was associated with an increased initial rise in insulin and gastric inhibitory polypeptide. The metabolic effects of the motilin infusion were overriden by the effects of somatostatin when both peptides were infused together; this suggests that somatostatin inhibits both the effects and secretion of motilin.
Adult↗
Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas).
During a six-year period (1973-9) 52 patients with pancreatic tumours and 10 with ganglioneuroblastomas were found to have raised plasma vasoactive intestinal polypeptide (VIP) concentrations. All the patients had severe secretory diarrhoea, weight loss, dehydration, hypokalaemic acidosis, and a raised plasma urea concentration. Reduced gastric acid secretion was seen in 72% of patients. Plasma VIP concentrations were not raised in patients with diarrhoea due to other types of tumour or disease or in hormone-secreting tumours not associated with diarrhoea. Plasma VIP measurement may therefore give clinical guidance in a patient with persistent watery diarrhoea and hypokalaemic acidosis. Surgical excision was clearly the treatment of choice, but metastatic pancreatic tumours usually responded to streptozotocin.
Adult↗
Plasma vasoactive intestinal polypeptide and other regulatory peptides in children with neurogenic tumours.
Plasma regulatory peptide levels were studied in a group of 21 children with neurogenic tumours and in 22 control children. Plasma vasoactive intestinal polypeptide (VIP) levels were significantly higher in children with neurogenic tumours than in normal children or those with other tumours (p less than 0.05). There was no significant difference between the groups in plasma levels of gastrin, pancreatic glucagon or pancreatic polypeptide. The plasma VIP level may thus be a helpful diagnostic marker for neurogenic tumours in children.
Adolescent↗
Effect of a long-acting octapeptide analogue of somatostatin on growth hormone and pancreatic and gastrointestinal hormones in man.
1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-D-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4--5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.
Gastrointestinal Hormones↗
Mixed pancreatic apudoma with symptoms of excess vasoactive intestinal polypeptide and insulin: improvement of diarrhoea with metoclopramide.
A female patient is described with a single pancreatic tumour producing vasoactive intestinal polypeptide (VIP), insulin, and pancreatic polypeptide. The initial presentation was with diarrhoea and hypokalaemia and a raised plasma VIP was demonstrated. Her symptoms improved with metoclopramide administration and absolute concentrations of 28 aminoacid (peak IV) VIP were found to have fallen. She then developed hypoglycaemia with hyperinsulinism. All symptoms resolved after surgical excision. This case emphasises the potential of these tumours to contain more than one endocrine cell type synthesising different biologically active peptides.
Apudoma↗
Somatostatin, gastrointestinal peptides, and the carcinoid syndrome.
During a control infusion noradrenaline and alcohol each provoked carcinoid flushing in four of five patients and pentagastrin in two of five patients. When tetradecapeptide somatostatin was infused on another day no patient flushed at any time, even when 16 microgram of either noradrenaline or pentagastrin were administered. Carcinoid flushing was not associated with release of gastrin or any of the other vasoactive or postprandially released gut regulatory peptides measured. In a sixth patient with severe prolonged carcinoid flushing, subcutaneous Des AA1, 2, 4, 5, 12D Trp8 somatostatin markedly reduced the incidence and severity of flushing for two days. Somatostatin is thus a potent inhibitor of carcinoid flushing, but no evidence has been found for the gut hormones measured to be mediators of flushing.
Aged↗
The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man.
The potency and specificity of somatostatin (SS) and four of its analogs were compared in seven patients with pancreatic endocrine tumors. The analogs tested were [D-Trp8]-SS, [D-Trp8, D-Cys14]-SS, Des-Asn5-[D-Trp8, D-Ser13]-SS, and Des (AA)1,2,4,5,12,13, [D-Trp8]-SS, and they did not show selective effects on the suppression of basal concentrations of GH, insulin, glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, motilin, enteroglucagon, or neurotensin. The observation that the potency of these analogs is similar to that of the parent molecule throws considerable light on the structure/activity relationship of the somatostatin molecule. Des-AA1,2,4,5,12,13, [D-Trp8]-Ss has been reported to have a prolonged action when administered sc. When administered iv, however, this octapeptide analog ws not long acting, suggesting that the prolonged action seen in the previous study was a result of delayed uptake from the injection site. An increment in plasma SS concentrations of 19 +/- 3 pmol/liter suppressed basal concentrations of GH, insulin, glucagon, and several gastrointestinal hormones by more than 50%, suggesting that even small changes in plasma SS levels may be physiologically important.
Adult↗
Effect of motilin on the gastric emptying of glucose and fat in humans.
The effect of natural motilin on the rate of gastric emptying of 200 ml 25% glucose was studied in seven subjects using a 99mtechnetium tin colloid marker. On the control day the subjects received intravenous saline while on the test day they received a motilin infusion of 0.2 pmol/kg/min. Infusions were blind and given in random order. Thirty minutes after glucose ingestion, 25.5 +/- 2% of the isotope had emptied during motilin infusion, compared with 11.0 +/- 1.5% with saline (p < 0.005). Plasma motilin concentrations rose from a basal value of 23 +/- 5 pM to 57 +/- 9 pM during the motilin infusion. The faster emptying rates after motilin were reflected in a faster rise of plasma glucose and insulin. The rate of emptying of 99mtechnetium-labeled double cream (200 ml, 24 g fat) was measured in 5 subjects. The rate of gastric emptying of the cream was unaffected by exogenous motilin. Gel chromatographic analysis of basal plasmas revealed two immunoreactive motilin peaks. After ingestion of cream during motilin infusion, there was an increase of the second peak but a reduction of the first peak whereas both peaks rose on the control day. Thus low-dose exogenous motilin stimulates the gastric emptying of glucose but not of fat.
Adult↗
Role of percutaneous transhepatic obliteration of varices in the management of hemorrhage from gastroesophageal varices.
One hundred and forty-one attempts at percutaneous transhepatic variceal obliteration were made in 116 patients with portal hypertension complicated by variceal hemorrhage. Varices were successfully obliterated in 80% of procedures and included 37 patients with continuous, acute variceal hemorrhage. Hemorrhage ceased immediately in these patients. Sixty-five percent of patients rebled a mean of 4.6 mo after successful transhepatic variceal obliteration. A randomized controlled trial against conventional medical therapy (29 treatment, 25 control) failed to show a significant reduction in death rate after transhepatic sclerotherapy, although the onset of further variceal hemorrhage was delayed. Follow-up portography in 50 patients demonstrated new vessel formation in 38 patients and recanalization of previously occluded varices in 5 patients. Complications arose in 29 of 141 procedures. There was one death but all the other complications responded to conservative management. Transhepatic variceal obliteration is an excellent, safe emergency treatment for variceal hemorrhage, especially in patients with decompensated liver disease. A high incidence of rebleeding is a long-term disadvantage and means that transhepatic variceal obliteration should not be used for the prophylaxis of variceal hemorrhage. Successful emergency treatment of variceal hemorrhage should be followed by elective portal decompression in suitable patients.
Adult↗