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

A 56-year-old man underwent distal pancreatectomy, splenectomy, and partial resection of the splenic flexure of the colon because of tumor in the tail of pancreas and the splenic hilus. The patient presented with symptoms of general malaise, anorexia, weight loss, mild diarrhea, and borderline diabetes mellitus, although there was no cholelithiasis. The diagnosis remained unclear until immunohistochemical studies of the resected specimen revealed somatostatin and synaptophysin, suggesting a somatostatinoma. Twenty-three reported cases of pancreatic somatostatinoma are reviewed and their clinical features discussed. The role of immunohistochemical studies in the diagnosis of somatostatinoma is described.
 ...
PMID:Pancreatic somatostatinoma: a case report and review of the literature. 196 77

As in diseases of other (neuro)endocrine glands, the pathology of the islets of Langerhans comprises both states of hypofunction, notably hypoinsulinism,--diabetes mellitus--and those of hyperfunction, such as hyperinsulinism from either nesidiodysplasia ("nesidioblastosis") or genuine islet-cell neoplasms. The pathogenesis of some characteristic structural lesions of these diseases of the islet parenchymal cells is reviewed against their neuroendocrine background, both phylogenetically and ontogenetically. A preliminary report is given of the appearance of argyrophil insulin cells during the normal foetal development of the islet parenchyma of the rabbit. In addition, the distribution of the newly discovered neuroendocrine markers synaptophysin and chromogranin A has been reviewed immunohistochemically in normal and neoplastic islet parenchyma cells; the insulin cells do not seem to contain chromogranin A.
 ...
PMID:Neuroendocrine background of the pathology of the islets of Langerhans. A minireview with particular reference to synaptophysin and chromogranin A as neuroendocrine markers and to the ontogeny of argyrophil insulin immunoreactive cells in the rabbit. 311 78

Neuropathies produced by both acrylamide- and streptozotocin-induced diabetes in the rat are accompanied by a deficit in the retrograde axonal transport of a defined group of proteins that can be visualized on two-dimensional polyacrylamide gels. In this work, these proteins are identified as being primarily soluble and being absent from rat brain. They are not immunologically related to the major retrogradely transported protein synaptophysin. Polyclonal antiserum to the proteins was produced in mice and used to confirm the reduction in their retrograde transport in sciatic nerve of diabetic and acrylamide-treated rats.
 ...
PMID:Subcellular distribution and immunological detection of retrograde axonally transported proteins in acrylamide and diabetic neuropathies. 750 89

The rapid spread of locally restricted neural and hormonal signals among the vast array of largely inexcitable corporal smooth muscle cells is an absolute prerequisite to normal erectile function. And yet the mechanism(s) responsible for this phenomenon is not well understood. As a first step toward a more integrative understanding of erectile physiology and/or dysfunction, an 8- to 12-wk period of experimental diabetes was induced in 2-mo-old male Fischer 344 rats by either intraperitoneal streptozotocin (STZ) injection (35 mg/kg; n = 22) or subtotal pancreatectomy (n = 11). Fourteen age-matched control animals received injection of vehicle only while nine others served as sham-operated control animals. Eight STZ-diabetic animals received insulin replacement. Erectile function was assessed by evaluation of penile reflexes and monitoring of intracavernous pressure responses to both electrical stimulation of the cavernous nerve and intracorporal papaverine or nitroglycerin injection. Intracavernous pressure responses to neurostimulation were significantly attenuated in both STZ-diabetic and subtotal pancreatectomy animals compared with age-matched control animals (P < 0.05). Penile reflexes were also significantly diminished (P < 0.05). Regression analysis revealed that diabetes-related decreases in neurostimulated intracavernous pressure responses were strongly correlated with diminished synaptophysin immunoreactivity in the corpora (P < 0.001; r = 0.88). However, there were no detectable diabetes-related differences in pharmacological erections induced by intracavernous papaverine or nitroglycerin injection. Northern analysis revealed a marked diabetes-related increase in the amount of connexin 43 mRNA measured in frozen corporal tissue. Insulin replacement partially restored (attenuated the loss of) synaptophysin immunoreactivity and maintained neurostimulated intracavernous pressure responses to control levels while having no effect on penile reflexes. These observations may have important implications to the understanding of erectile physiology as well as the etiology of diabetes-related erectile dysfunction.
 ...
PMID:Diminished neurogenic but not pharmacological erections in the 2- to 3-month experimentally diabetic F-344 rat. 913 84

Pancreatic beta-cells secrete insulin by Ca2+-triggered exocytosis of insulin-containing large dense-core vesicles. Synaptotagmin is a Ca2+/phospholipid-binding protein and is a good candidate for the Ca2+ sensor for exocytosis of synaptic vesicles in neurons. In the present study, we generated a polyclonal antibody against synaptotagmin III, and found that synaptotagmin III immunoreactivity was present at high levels in insulin-containing pancreatic islet cells and insulin-secreting clonal MIN6 cells. In subcellular fractionations of MIN6 cells, synaptotagmin III was recovered in the vesicular fractions containing both insulin and vesicle-associated membrane protein-2 (VAMP-2), but not in synaptophysin-positive fractions. The secretory vesicles immunoprecipitated by anti-VAMP-2 antibody contained synaptotagmin III and insulin. In addition, treatment of streptolysin-O-permeabilized MIN6 cells with anti-synaptotagmin III antibody significantly inhibited Ca2+-triggered insulin secretion. These results indicate that synaptotagmin III is localized in insulin-containing dense-core vesicles in pancreatic beta-cells, and further strongly suggest that synaptotagmin III is the Ca2+ sensor in the exocytosis of insulin secretory vesicles.
Diabetes 1997 Dec
PMID:Localization and functional role of synaptotagmin III in insulin secretory vesicles in pancreatic beta-cells. 939 87

Apoptosis appears to play an important role in the development of diabetes in the non-obese diabetic (NOD) mouse. Since the autoimmune process leading to the manifestation of insulin dependent diabetes mellitus (IDDM) can also affect the sympathochromaffin system, we analyzed the role of apoptosis and infiltration of the adrenal medulla as features of this autoimmune process in parallel with the development of diabetes. Prediabetic and diabetic NOD mice aged 3 to 30 weeks were studied and compared with control mice. Apoptosis was assessed by in situ end-labeling method and ultrastructural analysis. Adrenals were screened for lymphocytic infiltration by conventional hematoxylin-eosin staining. Chromaffin cells were characterized by immunohistochemical staining against synaptophysin and tyrosine hydroxylase. Apoptotic nuclei were detected in all mice studied at a very low level, mainly occuring within the connective tissue between medulla and cortex. The maximum score was achieved at 3 weeks (1.91+/-0.48 apoptotic cells/1000 counted cells; n = 4). There was no significant difference between NOD mice and control mice. No correlation could be found between blood glucose levels and apoptosis. On the ultrastructural level, apoptotic cells presented typical features of apoptosis, i.e. condensed nuclei and cytoplasm. Neither in NOD mice nor in controls lymphocytic infiltration or fibrosis of the adrenal was detected. Even NOD mice with overt diabetes did not exhibit morphological signs of medullitis. In summary, no signs of immune destruction of the adrenal medulla in NOD mice aged 3 to 30 weeks could be detected.
Exp Clin Endocrinol Diabetes 1998
PMID:Apoptosis in the adrenal gland of non-obese diabetic (NOD) mice. 1007 28

Pancreatic islet cells express receptors and transporters for L-glutamate and are thus believed to use L-glutamate as an intercellular signaling molecule. However, the mechanism by which L-glutamate appears in the islets is unknown. In the present study, we investigated whether L-glutamate is secreted through exocytosis by alphaTC6 cells (clonal mouse pancreatic alpha-cells). An appreciable amount of L-glutamate was released from cultured cells after the addition of KCl or A23187 in the presence of Ca2+ and 10 mmol/l glucose in the medium. The KCl-induced glutamate release was significantly reduced when assayed in the absence of Ca2+ or when the cells were pretreated with EGTA-AM. The KCl-induced Ca2+-dependent glutamate release was inhibited approximately 40% by voltage-gated Ca2+ channel blockers, such as nifedipine at 20 micromol/l. The degree of KCl-induced Ca2+-dependent glutamate release was correlated with an increase in intracellular [Ca2+], as monitored by fura-2 fluorescence. Botulinum neurotoxin type E inhibited 55% of the KCl-induced Ca2+-dependent glutamate release, followed by specific cleavage of 25 kDa synaptosomal-associated protein. Furthermore, bafilomycin A1, a specific inhibitor of vacuolar H+-ATPase, inhibited 40% of the KCl-induced Ca2+-dependent glutamate release. Immunoelectronmicroscopy with antibodies against synaptophysin, a marker for neuronal synaptic vesicles and endocrine synaptic-like microvesicles, revealed a large number of synaptophysin-positive clear vesicles in cells. Digitonin-permeabilized cells took up L-glutamate only in the presence of MgATP, which is sensitive to bafilomycin A1 or 3,5-di-tert-butyl-4-hydroxybenzylidene-malononitrile (a proton conductor) but insensitive to either oligomycin or vanadate. From these results, it was concluded that alphaTC6 cells accumulate L-glutamate in the synaptophysin-containing vesicles in an ATP-dependent manner and secrete it through a Ca2+-dependent exocytic mechanism. The Ca2+-dependent glutamate release was also triggered when cells were transferred in the medium containing 1 mmol/l glucose, suggesting that low glucose treatment stimulates the release of glutamate. Our results are consistent with the idea that L-glutamate is secreted by alpha-cells through Ca2+-dependent regulated exocytosis.
Diabetes 2001 May
PMID:Ca2+-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic alpha-cells. 1133 3

Diabetes is known to be one of the risk factors for dementia; however, neuropathic changes in the brain of patients with the disease have not been completely revealed. So in the present study, we investigated the brain function of rats with diabetes induced by streptozotocin (STZ), one of the most commonly used animal models for diabetes. In the diabetic rats, immediately working memory performance was impaired in the Y-maze task and neuronal cytoskeleton proteins such as calbindin, synaptophysin, and syntaxin were reduced. Furthermore, morphological observation by Golgi staining showed a decrease in the number of basal dendrites and abnormality of spine structure. Next, we measured the content of brain-derived neurotrophic factor (BDNF) in the diabetic brain, because BDNF is one of the essential proteins for the maintenance of neuronal functions including synapse function and neuronal transmissions. In the diabetic brains, both protein and mRNA levels of BDNF were severely reduced. These results suggest that, in diabetes, synapse dysfunction is, at least in part, caused by a failure of BDNF synthesis in the brain.
 ...
PMID:Diabetic neuropathies in brain are induced by deficiency of BDNF. 1220 Feb

We present 12 patients with 20 plexiform xanthomatous tumors (PXTs). All patients were male. Patient ages ranged from 20 to 59 years (mean 45 years). Clinical information was available for 11 (92%) patients. Only one patient with markedly elevated cholesterol levels had a family history of hypercholesterolemia; none of the others had a family or personal history of diabetes mellitus, hypercholesterolemia, or hyperlipoproteinemia. Three patients had markedly elevated serum triglyceride levels. The tumors were solitary in seven patients and multiple in five patients: three patients had two tumors, one presented had three, and one had four. PXTs were located on the knee (n = 8), elbow (n = 5), foot or hand (n = 3), and one each on the Achilles tendon, buttock, toe, and back. PXT was white to yellow in color and ranged in size from 0.7 to 5 cm (mean 2.7 cm). The tumors were located in the dermis and subcutis, had a distinctive plexiform arrangement, and were composed of various admixtures of uniform epithelioid and xanthomatous cells. All tumors in patients with solitary or multiple lesions had a plexiform architecture. Most of the nodules of the plexiform pattern of PXTs measured 0.5-2 mm. Rarely cholesterol clefts, necrosis, sparse inflammation, and multinucleated Touton giant cells were present. In two patients with multiple tumors, the PXT completely lacked the xanthoma cells and thus resembled an epithelioid lesion. Immunohistochemically, all lesions were KP1 (CD68) and vimentin positive and lysozyme, S-100 protein, HMB-45, epithelial membrane antigen, cytokeratins, factor VIIIrag, CD34, muscle-specific actin, alpha-smooth muscle actin, desmin (D33), desmin (Der-11), chromogranin, synaptophysin, neurofilament protein, and glial fibrillary acidic protein negative. Two patients with multiple lesions noted recurrences over 10 years. With the exception of one patient who died of an unknown cause, all 10 patients with follow-up were alive, some with residual disease, over a mean of 9 years (range 1-25 years). Some PXTs may represent a morphologic variant of tuberous or tendinous xanthoma, yet its exclusive occurrence in men, absence of personal/familial hyperlipemia/hypercholesterolemia in some patients, and relative paucity of inflammation and cholesterol clefts may make this a distinctive entity.
 ...
PMID:Plexiform xanthomatous tumor: a report of 20 cases in 12 patients. 1236 45

Adrenal cortical phaeochromocytomas (pseudo-phaeochromocytomas) are a very rare entity and a diagnostic challenge. Of the few cases previously reported, most have incomplete data or lack clinical and biochemical follow-up documenting the cure of the excess secretion of catecholamines after resection of the tumour. We report herein a 62-year-old patient with clinical and biochemical findings diagnostic of a phaeochromocytoma associated with a 2-cm adrenal mass on CT scan. Surgery revealed the presence of an adrenal cortical adenoma with positive staining for the neuroendocrine marker synaptophysin, but negative for chromogranin, as has been previously reported for these rare cortical phaeochromocytomas. After removal of the tumour the clinical symptoms resolved and biochemical markers normalized, demonstrating the causal relationship between the cortical tumour and the excess production of catecholamines.
Exp Clin Endocrinol Diabetes 2003 Apr
PMID:Adrenal cortical phaeochromocytoma: a case report of a rare entity. 1274 63


1 2 3 4 5 6 7 8 9 Next >>