Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Natural Somatostatin has a short half-life (3 min), is only active after intravenous administration and causes a rebound hypersecretion of hormones after discontinuation of administration. Recently a long-acting powerful Somatostatin analog was developed (SMS 201-995; Sandostatin) which has a half-life of 113 min after subcutaneous administration. After administration of this analog no rebound hypersecretion of hormones was observed. In the present review the effects of the acute administration and of long-term treatment with SMS 201-995 in acromegalic patients is discussed. In addition the potential role of therapy with Somatostatin analogs and the preliminary effects of Somatostatin and/or SMS 201-995 are discussed in disorders of gastro-intestinal function (haemorrhages, diarrhoea, pancreatitis and endocrine pancreatic tumours), diabetes mellitus, central nervous system disturbances and oncology. Finally, several aspects of the tolerance, tachyphylaxis and side effects of SMS 201-995 are discussed.
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PMID:Non-pituitary actions of somatostatin. A review on the therapeutic role of SMS 201-995 (sandostatin). 287 90

SMS 201-995 (Sandostatin) was studied using low doses (50 to 100 micrograms) administered subcutaneously every 12 hours. A single 50-micrograms dose of SMS 201-995 effectively controlled gastric acid and blood gastrin levels for 12 hours in three patients with benign gastrinomas and was useful in their perioperative management. Higher doses of the agent (500 to 800 micrograms per day) had no effect on metastases in one of two patients with metastatic gastrinoma. In the other patient, one tumor shrank but the other continued to grow after three months of treatment while serum gastrin levels did not change. Cultured metastatic tumor tissue from this patient released different forms of gastrin; growth rates varied, independent of uptake of SMS 201-995, and gastrin release increased. A neonate with nesidioblastosis maintained normal blood glucose levels while receiving SMS 201-995 therapy following a 95 percent pancreatic resection. In two elderly patients with organic hypoglycemia--one with a single benign adenoma and one with multiple adenomatosis--the somatostatin analogue did not prolong the hypoglycemia-free interval. In nine patients with carcinoid syndrome, flushing was uniformly controlled with 50 micrograms of SMS 201-995 administered every eight to 12 hours. One of the nine required exocrine pancreatic replacement. After six months of treatment, three of the nine had no change in tumor size and one had remission of symptoms and stopped treatment. In two patients with vipoma, SMS 201-995 controlled diarrhea and reduced levels of vasoactive intestinal peptide; tumor necrosis occurred in one patient. In a patient with diabetic diarrhea unresponsive to all treatments, SMS 201-995 therapy controlled the diarrhea but did not interfere with control of the diabetes.
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PMID:Somatostatin analogue (SMS 201-995) in the management of gastroenteropancreatic tumors and diarrhea syndromes. 287 47

Because of its wide distribution in the organism, natural somatostatin (SRIF) demonstrates an ample spectrum of actions, involving mainly the central neuroendocrine system and the enteropancreatic area. In the former, this peptide may find its field of application in conditions characterized by excessive GH, TSH or ACTH secretion, depending on the central or peripheral cause of the inappropriate hormone control. The inhibitory effect of SRIF on gastrointestinal and pancreatic hormones may be useful in the management of tumors originating in this system and also in the treatment of inflammatory processes such as pancreatitis, in malignant diarrhea, and in gastrointestinal bleeding. A complex action of SRIF and its derivative on insulin release and glucose homeostasis may offer some advantages in the control of unstable diabetes. Dampening of organic functions in the upper digestive tract may also render SRIF and its analogues useful in the exploration of the gallbladder, gastric and pancreatic functions. The effect of such peptides on tissue growth and on the regulation of blood pressure are the subject of present investigations. Cytoprotection, an interesting aspect of SRIF application, is discussed elsewhere in this compendium. Finally, some comments on the possible use of SRIF as an additive to the conventional treatment of burns and sepsis close this review.
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PMID:Clinical applications of somatostatin. 290 Feb 4

The study has examined the effect of streptozotocin-induced diabetes of 3 days and 10 weeks duration upon the serotonin content of the rat pancreas and small intestine. Streptozotocin administration (65 mg/kg) resulted in a significant (p less than 0.001) decrease in pancreatic serotonin after 3 days (to 18% of the non-diabetic content). Diabetes of both short- and medium-term duration had no significant effect upon the serotonin content of the small intestine suggesting that changes in mucosal serotonin levels are not responsible for the diarrhea frequently observed in streptozotocin-treated animals. The diabetogenic effect of streptozotocin and the reduction in pancreatic serotonin were abolished by prior injection of nicotinamide thus providing further evidence for co-storage of insulin and serotonin in the B cell.
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PMID:Effect of streptozotocin administration upon the serotonin content of the pancreas and small intestine of the rat. 294 36

Small intestinal permeability to mannitol and lactulose was studied in 12 patients aged 36-70 (mean 56) years with diabetic diarrhoea (DD). Ten uncomplicated diabetics aged 24-56 (mean 37) years and 25 normal subjects aged 22-60 (mean 37) years served as controls. Permeability was assessed by measuring urinary recovery of the test substances after oral ingestion. Mean lactulose excretion in patients with DD was significantly lower than in normal controls but was not significantly different from the uncomplicated diabetics. Mean lactulose excretion was not significantly different in the three groups. However, lactulose to mannitol excretion ratios (LMER) were significantly higher in patients with DD compared to the controls or the uncomplicated diabetics. LMER in seven patients with DD were outside the normal range. LMER in patients with DD did not correlate with blood urea, small intestinal transit time, faecal fat excretion, small intestinal bacterial overgrowth, duration of diabetes or duration of diarrhoea. Jejunal morphology was normal in all patients with DD. It was concluded that small intestinal permeability was abnormal in some patients with DD and that this might be a factor in the aetiology of the diarrhoea.
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PMID:Intestinal permeability in diabetic diarrhoea. 295 Dec 20

Diarrhea was noted in rats with streptozocin-induced chronic diabetes. We have investigated the possibility that this diarrhea is a consequence of altered neuronal control of water and electrolyte absorption in the intestinal epithelium. In particular, we examined noradrenergic control because alpha-2-adrenergic agonists are known to stimulate intestinal fluid absorption. When compared with nondiabetic littermates, chronically diabetic rats exhibited significant impairment of fluid absorption by the ileum and colon, but not the jejunum. This impairment of intestinal fluid absorption was not found in either insulin-treated or untreated acutely diabetic (7 d) animals. Mucosal histology appeared normal in all of the above groups. Mucosal norepinephrine stores in the jejunum and ileum of chronically diabetic rats were estimated in vitro by the short-circuit current (Isc) response to tyramine, an agent that effectively releases stored norepinephrine. Pargyline was added to inhibit enzymatic destruction of the added tyramine. In chronically diabetic rats, the Isc response to tyramine was significantly decreased in ileum, but not in jejunum. However, when these responses were expressed as a fraction of the maximal Isc tissue response to exogenously added epinephrine, significant decreases were noted in both ileum and jejunum. In tissues from acutely diabetic rats, Isc responses to tyramine and epinephrine were no different from controls. When sympathetic denervation was produced in nondiabetic rats by treatment with 6-OH-dopamine, the pattern of impaired fluid absorption that developed was the same as that observed in chronically diabetic rats. We conclude that impaired intestinal mucosal absorption of fluid and electrolytes slowly develops in rats made diabetic with streptozocin and that this absorptive impairment is due to a loss of normally present noradrenergic innervation of enterocytes.
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PMID:Diarrhea in streptozocin-treated rats. Loss of adrenergic regulation of intestinal fluid and electrolyte transport. 298 8

Celebes black macaques (Macaca nigra) with a history of diabetes mellitus, recurrent bacterial and protozoal infections, diarrhea, anemia, weight loss, anorexia, and a high mortality were studied to determine their immune status. Two groups of monkeys, healthy and unhealthy, were formed on the basis of a clinical assessment. The proliferative response and the pokeweed-mitogen-induced polyclonal IgG response of peripheral blood mononuclear cells of unhealthy monkeys were significantly less than the responses of healthy monkeys. The percentage of HLA-DR+ cells varied greatly in unhealthy monkeys. The OKT4/OKT8 ratios of unhealthy monkeys were generally greater than the ratios of healthy monkeys. Unhealthy monkeys usually had smaller percentages of OKT8+ cells than did healthy monkeys. The two groups of monkeys were examined for the presence of a syncytial forming retrovirus by a coculture assay involving Raji cells, a human B lymphoblastoid cell line. A type D retrovirus was detected in the unhealthy group but not in the healthy group. Retroperitoneal fibromatosis was detected in several monkeys in the unhealthy group.
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PMID:Virus-associated deficiencies in the mitogen reactivity in celebes black macaques (Macaca nigra). 300 Jun 62

A case of a 58-year-old woman with an unusual variant of malignant islet-cell tumor showing oncocytic features is described. Using the light microscopy technique, the tumor appeared comprised of solid nests of uniform cells with abundant, eosinophilic cytoplasm and round nuclei with granular chromatin. Ultrastructurally, the cells contained numerous abnormal mitochondria, dilated rough endoplasmic reticulum, and scattered dense-core neurosecretory granules, often associated with cytoplasmic filaments. Tumor cells were focally immunoreactive for insulin, glucagon, and somatostatin and diffusely immunoreactive for alpha 1-antitrypsin as assayed by the avidin--biotin technique. The tumor was immunonegative for human chorionic gonadotropin, gastrin, adrenocorticotropic hormone, and serotonin. The patient exhibited some of the clinical features associated with glucagonoma syndrome, including diabetes mellitus and chronic diarrhea. The tumor behaved in a malignant fashion, with widespread lymphatic involvement and bony metastases at the time of presentation. This report of an oncocytic islet-cell carcinoma supports the concept of oncocytic differentiation in islet-cell tumors in a fashion analagous to oncocytic carcinoids.
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PMID:Functioning oncocytic islet-cell carcinoma. Report of a case with electron-microscopic and immunohistochemical confirmation. 300 44

The normally functioning immune system is subject to intricate networks of regulatory mechanisms: it is therefore not surprising to find that autoimmune diseases present a complex pathogenic picture in which the relative contributions of various factors probably determine the precise nature and course of disease. This is particularly evident in the effector mechanisms of organ-specific autoimmunity which are described in this chapter. These ultimately give rise to the disease symptoms, and can be directly cytotoxic, or may either stimulate or block functional activity or growth of the target cells. Their various contributions to human diseases are becoming more firmly established, as in Type I diabetes, or are only now being described, as in the case of EC-Ab in protracted diarrhea of infancy and as evidenced by the growing lists of receptor-stimulating or -blocking antibodies. The nature and precise location of relevant autoantigens is also coming under closer scrutiny. The answers to the question of why these diseases arise in the first place remain more elusive. However, it is again likely that a variety of factors can contribute. The attractive possibility of a role for idiotypic interactions is gaining ground, particularly within the context of antibodies to hormones and their receptors. Another potential mechanism which we believe may be of central importance, particularly in the development of organ-specific destructive autoimmunity, and which we have discussed here in detail, is the aberrant expression of HLA Class II molecules by target cells. Whether this is actually an initiating factor is presently not known, but its potential for promoting pathogenesis both early and late in the process is clear. Furthermore, the complex nature of the regulation of epithelial Class II expression may help to explain the heterogeneity of features and course of disease in different patients with the same underlying pathology. All these advances in our basic understanding of the disease processes should ultimately lead to more effective and specific means of therapeutic intervention.
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PMID:Organ-specific autoimmunity: a 1986 overview. 302 54

We describe a patient with a small somatostatinoma of the papilla of Vater without clinical evidence for diabetes mellitus, diarrhea, steatorrhea, or cholelithiasis, showing normal plasma basal levels for somatostatinlike immunoreactivity. The diagnosis was based on histologic and immunohistochemical analysis of tumor tissue and hypersomatostatinemia induced by the calcium-pentagastrin test. Before removal of the tumor both diagnostic tests recommended for the detection of a somatostatinoma, a tolbutamide test and a calcium-pentagastrin test, were performed. Whereas the calcium-pentagastrin test provoked a markedly elevated plasma somatostatin level in association with a depressed plasma neurotensin level, the tolbutamide test surprisingly did not. After removal of the tumor the calcium-pentagastrin test no longer induced hypersomatostatinemia. Further studies are needed to determine whether the calcium-pentagastrin test is a more reliable diagnostic test than the tolbutamide test in somatostatinomas with normal plasma basal levels.
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PMID:Comparative diagnostic value of the calcium-pentagastrin test versus the tolbutamide test in a patient with a somatostatinoma. 302 98


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