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)

1. Immunohistochemical, immunoblotting and release experiments were performed on ileum from control rats, from 8-week streptozotocin-diabetic rats and from diabetic rats after acute application of insulin in vitro. 2. There was an increase in vasoactive-intestinal-polypeptide-like and a decrease in calcitonin-gene-related-peptide-like immunoreactivity in the myenteric plexus of the diabetic rat ileum, although electrically evoked release of both peptides from enteric nerves was defective. Acute application of insulin in vitro reversed the defective release and changes in immunoreactivity of vasoactive intestinal polypeptide and calcitonin-gene-related peptide seen in the enteric nerves of streptozotocin-diabetic rat ileum. 3. In addition, using a monoclonal neurofilament antibody RT 97 that recognizes a phosphorylated neurofilament epitope present in normal enteric nerves, it was shown that this phosphorylated neurofilament epitope was absent in diabetic nerves, even though a polyclonal neurofilament antibody revealed that neurofilaments were present in both axons and cell bodies of the myenteric plexus of diabetic rat ileum. After only 2 h of insulin incubation in vitro, the phosphorylated neurofilament epitope was again present in the nerves. 4. It is suggested that the abnormal distribution of phosphorylated neurofilaments and defective storage and release of vasoactive intestinal polypeptide and calcitonin-gene-related peptide in the present study may be a more general feature of diabetes. The restoration of these abnormalities by continuous acute insulin application in vitro shown here suggests that the availability of a steady level of insulin might prevent some of the changes which occur in early stages of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversal of nerve damage in streptozotocin-diabetic rats by acute application of insulin in vitro. 306 14

A novel putative polypeptide hormone identified as islet amyloid polypeptide (IAPP) was recently purified from islet amyloid (IA) of diabetic humans and cats, and also from amyloid of a human insulinoma. Although the function of IAPP is yet unknown, its occurrence in pancreatic endocrine tissue and its partial amino acid sequence identity with calcitonin gene-related peptide (CGRP) suggests an endocrine regulatory effect. In the present investigation, the authors utilized antisera to insulin, glucagon, somatostatin, pancreatic polypeptide, synthetic human CGRP, and a synthetic human IAPP (7-17) undecapeptide to immunohistochemically (PAP technique) document the presence of IAPP immunoreactive cells in the islets of the cat, dog, mouse, and rat, but not in the islets of the horse or calf. In serial sections of islets from these species it was shown that IAPP immunoreactivity occurred in insulin-reactive beta cells. This observation was confirmed immunocytochemically in cat islets by means of protein A-gold probes. With protein A-gold labeling techniques, IAPP immunoreactivity was localized to the outer lucent compartment of the beta cell secretory granule, whereas insulin immunoreactivity was associated with the electron-dense core. These findings provide strong evidence that IAPP or an IAPP precursor is synthesized by beta cells and is stored in beta cell granules for subsequent co-secretion with insulin. The conservation of IAPP in humans and multiple animal species and the localization of IAPP to pancreatic beta cells provide further evidence that IAPP has an important endocrine regulatory function. The propensity of IAPP to polymerize and form IA fibrils in diabetes associated with aging may indicate that IAPP is in some way also linked to the development of Type 2 diabetes.
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PMID:Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. 327 6

Central and lateral hypothalamic concentrations of 10 regulatory peptides were measured by radioimmunoassay in streptozocin-induced diabetic (STZ-D) and matched control rats between 1 day and 14 wk after diabetes induction. After 2 wk, both central and lateral hypothalamic neuropeptide Y (NPY) concentrations in STZ-D rats were consistently higher than those found in control rats, with significant 30-50% increases at 4 wk in the central hypothalamus, and at 6 and 14 wk in both central and lateral hypothalamus. Immunocytochemical studies in 4- and 6-wk STZ-D animals showed the appearance of intensely NPY-positive swollen cell bodies in the supraoptic nucleus and a subjective increase in NPY staining of medial hypothalamic nerve fibers. Central hypothalamic concentrations of three other peptides were significantly greater in STZ-D animals than those in control animals at single points (neurotensin, 1 day; calcitonin gene-related peptide, 2 wk; neurokinin, 4 wk). Hypothalamic concentrations of the other six peptides examined (bombesin, galanin, neuromedin B, substance P, somatostatin, and vasoactive intestinal peptide) did not differ significantly between STZ-D and control groups at any time. However, galanin immunostaining in the supraoptic and magnocellular paraventricular nuclei was strikingly concentrated in a reduced number of distended cell bodies. Hypothalamic peptide changes in STZ-D could be related to metabolic disturbance, changes in energy and water balance, altered pituitary function, or other factors. Persistently elevated concentrations of NPY, a very potent central stimulant of eating and drinking, may mediate the hyperphagia and polydipsia characteristic of STZ-D.
Diabetes 1988 Jun
PMID:Increased hypothalamic neuropeptide Y concentrations in diabetic rat. 328 97

Amyloid deposition is a very typical alteration in the islets of Langerhans in human Type 2 (non-insulin-dependent) diabetes mellitus and in feline diabetes mellitus. Amyloid infiltration is also commonly found in insulin-producing pancreatic tumors. It was shown recently that amyloid purified from an insulinoma was composed mainly of a novel polypeptide (insulinoma amyloid polypeptide, IAPP), which had partial identity with the neuropeptide calcitonin gene-related peptide (CGRP). Cat islet amyloid contained a similar polypeptide. This finding is verified in the present study, and it is shown that the cat IAPP differs from the human peptide only in two of the 16 elucidated amino acid residues. The authors now also show by N-terminal amino acid sequence analysis that human islet amyloid is of IAPP origin. Although the significance of IAPP is unknown, its occurrence in pancreatic endocrine tissue and partial identity with a known neuropeptide suggests an endocrine regulatory function.
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PMID:Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats contains a novel putative polypeptide hormone. 329 68

A novel peptide, islet amyloid polypeptide (IAPP), with structural resemblance to calcitonin gene-related peptide has recently been purified from amyloid deposits in an insulinoma and from islets of Langerhans. By immunohistochemical methods, using antisera to a synthetic undecapeptide of IAPP and to insulin, we show that freshly fixed islet B cells in man, guinea pig, rat, mouse and hamster exhibit strong IAPP-immunoreactivity while A cells are unreactive. In human autopsy material, all of 11 non-diabetic individuals had IAPP immunoreactivity of the islets. In comparison 8 of the 13 patients with Type 2 (non-insulin-dependent) diabetes had no IAPP immunoreactive cells. The proportion of islet cells having IAPP immunoreactivity exceeded 10% in only 1 of the 5 remaining diabetic patients while in all 13 patients substantially more than 10% of the islet cells contained immunoreactive insulin. IAPP-positive amyloid deposits were found in 20-99% of the islets in 12 of the Type 2 diabetic patients while 6 of 11 non-diabetic subjects had amyloid in 3-11% of their islets. In islets with IAPP-immunoreactive amyloid, very few IAPP-cells were seen despite a strong reaction of the B cells with antiserum to insulin. This study shows that IAPP is a normal islet B cell component and that IAPP immunoreactivity in B cells is diminished in Type 2 diabetes while IAPP is deposited as amyloid fibrils in the islets of Langerhans. Although the function of IAPP is unknown, its occurrence in the islet B cells and its structural relation to calcitonin gene-related peptide makes a hormonal nature probable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals. 332 23

In experimental alloxan diabetes marked hypocalcemia and hyperglycemia are observed in the blood of rats during the acute period of the disease (from 1.5 to 2 months). After 2.5-3.5 months of diabetes calcium level reaches the upper normal limit. Simultaneously, antibodies to calcitonin appear. It is quite likely that excessive calcitonin secretion, leading to hypocalcemia, decreased insulin secretion and hyperglycemia take place in the acute stage of diabetes. When diabetes persists the antibodies to calcitonin which reveal a homeostatic reaction blocking the excess of calcitonin appear. This normalizes the level of calcium in the blood and prevents the further increase in the blood sugar level.
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PMID:[Homeostatic role of calcitonin antibodies in calcium metabolism in experimental diabetes mellitus]. 334 43

The distribution of calcitonin gene-related peptidelike immunoreactive (CGRP-LI) nerve fibers in the myenteric plexus of ileum and proximal colon of rats 8 wk after induction of diabetes with streptozotocin was studied using immunohistochemical techniques. A marked decrease in CGRP-LI nerve fibers mainly around the ganglion cells of the myenteric plexus of both ileum and proximal colon was observed in diabetic rats. The sparsely located immunoreactive nerve cell bodies in the control rats were absent in the diabetic preparations. There were, however, intensely stained CGRP-LI varicose nerve fibers that ran through the internodal strands and over the myenteric ganglia of the diabetic intestines. These findings indicate the presence of CGRP-LI nerve fibers of dual origin in the intestinal wall. The absence of positive cell bodies and diminished CGRP-LI nerve fibers around the ganglion cells in the diabetic tissues suggest that the state of diabetes selectively affects CGRP-LI nerve fibers of intrinsic rather than extrinsic origin. Furthermore, the absence of change in substance P-like immunoreactivity in the enteric system of rats with streptozotocin-induced diabetes of the same duration suggests that calcitonin gene-related peptide and substance P are contained in different populations of intrinsic nerve fibers in the gastrointestinal tract of the rat.
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PMID:Selective damage of intrinsic calcitonin gene-related peptide-like immunoreactive enteric nerve fibers in streptozotocin-induced diabetic rats. 349 87

Calcitonin is known to inhibit secretion of gastrin and insulin in vivo. The objective of this study was to determine whether calcitonin can act directly on pancreatic islets in vitro to inhibit insulin release. Isolated islets were obtained from collagenase-treated rat pancreas, and three peptides (gastrin-releasing peptide, cholecystokinin-8, bombesin) and glucose were used to stimulate insulin release. All agents caused a significant increase in insulin secretion and calcitonin inhibited these responses, but had no consistent effect on basal release. This study provides evidence that calcitonin is an effective inhibitor of insulin secretion and acts directly on islet tissue.
Diabetes 1986 Jan
PMID:Calcitonin inhibition of insulin release from isolated rat pancreatic islets. 351 Jan 39

In eight normal pregnant women and in eighteen women with a family history of diabetes, plasma calcitonin (CT), parathyroid hormone (PTH), insulin and glucagon variations and total plasma calcium levels were investigated. Calcitonin, parathyroid hormone and glucagon were all increased during the 2nd and 3rd trimester of pregnancy in normal women (N.W.) and in women with a family history of diabetes (W.F.H.D.). Plasma calcitonin levels were statistically significantly different between the two groups only in the 3rd trimester (118 +/- 4.9 vs 139 +/- 3.6 pg/ml p less than 0.01 in N.W. and W.F.H.D. respectively). Total plasma calcium levels were decreased significantly in the 3rd trimester in both groups: 3rd vs 1st trimester p less than 0.005 and p less than 0.001 in N.W. and W.F.H.D. respectively. Statistically significant difference between the two groups in total insulinemic area (p less than 0.001), in the rapid phase area (p less than 0.01) and insulinogenic index (p less than 0.05) were observed in the 3rd trimester.
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PMID:Plasma calcitonin variations in normal women and in women with family history of diabetes during pregnancy. 354 28

The effect of streptozotocin (STZ) induced diabetes on rat urinary bladder function was investigated by means of 'in vivo' cystometry and 'in vitro' recording of bladder strips contractility. A group of sucrose-fed animals was included to determine to what extent the STZ-induced changes were ascribable to the increased diuresis. After 7-9 weeks from STZ injection there was a marked increase in weight of bladder and ureters. Cystometry revealed a marked increase in bladder capacity (volume threshold) although pressure threshold and amplitude of micturition contraction were unaffected. Sucrose-fed animals, having normal blood glucose levels but a similar increase in urine production exhibited cystometric changes identical to those of STZ animals. 'In vitro' experiments indicated that the response to field stimulation (0.1-20 Hz) is reduced in STZ-pretreated but increased in sucrose-fed animals, as compared to controls. The content of urinary bladder and ureters in sensory neuropeptides (substance-P, neurokinin-A and calcitonin-gene related peptide-like immunoreactivity) was increased by STZ diabetes when values were corrected for the increased weight of these organs. The capsaicin-induced contraction of the rat isolated bladder strips, presumably caused by neuropeptides released from intramural sensory nerves, is unaffected by STZ diabetes. These findings indicate that STZ diabetes produces, at an early stage, changes similar to those reported to occur in the human disease, e.g. a greater bladder capacity with unimpaired voiding function. The increased bladder capacity of STZ-rats seems largely, if not solely, ascribable to changes in physical properties of the detrusor muscle, thereby allowing accommodation of greater than normal volumes with similar increase of intraluminal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cystometric changes in the early phase of streptozotocin-induced diabetes in rats: evidence for sensory changes not correlated to diabetic neuropathy. 361 89


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