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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further evaluate whether transsynaptic mechanisms account for stress-induced changes in adrenomedullary preproenkephalin mRNA (ppEnk mRNA), neonatal rats were made hypoglycemic at a time when synapses are non-functional (less than 10 days postnatal age). While ppEnk mRNA in medullae from adult rats increased as much as 60-fold in this paradigm (insulin 10 U/kg), ppEnk mRNA levels in the newborn increased only 1.6-fold (insulin 20 U/kg). To evaluate whether postsynaptic cholinergic pathways of the neonatal adrenal medulla were functional, we treated 5-day-old pups with cholinergic agonists (nicotine [1 mg/kg, s.c., q 12 h] + carbachol [1.7 mumol/kg, s.c., q 12 h x 4 days]). Combined cholinergic agonist treatment augmented enkephalin prohormone and peptide levels up to 3-fold (P less than 0.05). To determine whether the blunted response to hypoglycemia in the newborn resulted from a deficiency in functional transsynaptic activity, synapses were matured using thyroid hormone pretreatment (postnatal days 2 and 3) before hypoglycemic stress. Hypoglycemia now caused a 40-fold increase in adrenomedullary ppEnk mRNA levels only in the T3/insulin treated group. To exclude other secondary effects of hypoglycemia (eg. hormonal, or insulin treatment-dependent), intracellular glycopenia was produced in the presence of secondary hyperglycemia by injecting adult rats or pups with 2-deoxyglucose (500 mg/kg). Similar to the insulin-hypoglycemia group, a large increase in adrenomedullary ppEnk mRNA resulted in the adult but not in the 5-day-old neonatal adrenal medullae. We conclude that enkephalin biosynthesis, like co-stored catecholamines, is induced by a transsynaptic process.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1992 Apr
PMID:Regulation of adrenomedullary preproenkephalin mRNA: effects of hypoglycemia during development. 131 92

Glucagon-like peptide-1 (GLP-1) is the main product of the intestinal processing of proglucagon. It is released from the intestinal K-cells into the circulation in response to the oral ingestion of food. At the pancreatic beta cell GLP-1 is a potent insulin secretagogue in the presence of elevated glucose levels, defining glucagon-like peptide-1 as a new incretin. Its action is mediated by specific receptors coupled to the adenylate cyclase system by a stimulatory G-protein. Finally, glucagon-like peptide-1 stimulates proinsulin gene expression and it is thus involved at several levels in the regulation of insulin synthesis and secretion.
Mol Cell Endocrinol 1992 May
PMID:Glucagon-like peptide-1(7-37)/(7-36)amide is a new incretin. 138 25

In order to elucidate the association between hyperglycemia and the vascular complications of diabetes, the effects of high glucose concentrations on the migration, proliferation and tube formation of bovine carotid artery endothelial cells were investigated. Cells treated with 16.7 and 33.3 mM glucose for 6 days showed 1.69- and 1.75-fold increase in serum-induced migration compared with cells treated with 5.6 mM glucose (p less than 0.05). The effect of glucose on cell proliferation was affected by serum concentration. When this was below 0.5%, a high glucose concentration stimulated cell growth to a maximum of 1.73 times that at a serum concentration of 0.05% (p less than 0.01) whereas at a serum concentration of 10%, growth was inhibited (p less than 0.05). Tube formation was studied by culturing the cells between two layers of collagen gel. Ultrastructurally, tubular structures were composed of one to several endothelial cells containing pinocytotic vesicles and cytoplasmic projections, and linked by junctional complexes. A basal lamina-like structure surrounded the abluminal surface. Treatment of the cells with 16.7 and 27.8 mM glucose for 4 days stimulated tubular elongation 1.85 and 1.71 times, respectively (p less than 0.01). Other osmogenic molecules such as mannitol and sucrose did not affect tube formation. These data imply that high glucose concentrations mimicking diabetic hyperglycemia may not inhibit the repair of endothelial injury and could act as a stimulator of neovascularization.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Effects of glucose on migration, proliferation and tube formation by vascular endothelial cells. 168 13

One of the hypotheses trying to explain the process of aging is the idea of glycation of proteins. This reaction, also called the Maillard or browning reaction, may explain age-related symptoms such as cataract, atherosclerosis and modification of collagen-containing tissues. Diabetics, which possess elevated blood sugar levels, show signs of accelerated aging exposing similar complications. The Maillard reaction, which occurs on a large scale in vivo, may play a key role in the initiation of these symptoms.
Mol Biol Rep 1991 May
PMID:The role of glycation in aging and diabetes mellitus. 174 74

The effect of neurotropin (NSP) in combination with streptozotocin (STZ) and cyclophosphamide (CY) on blood glucose and pancreatic histopathology on day 7 and day 14 after the initiation of the treatment was studied in C57Bl/6 male mice. STZ (40 mg/kg) and NSP (1 mg/kg) were applied intraperitoneally on five consecutive days and CY (150 mg/kg)--twice on day 1 and day 3. In single B cells dilatation of the endoplasmic reticulum was found. On day 7 in proximity to some endocrine cells in the mice treated with STZ, STZ + CY + NSP and STZ + CY macrophages were observed. On day 14 lymphocytic infiltration of the islets was demonstrated only in the groups of mice injected with STZ, STZ + CY while in the group treated with the combination STZ + CY + NSP no infiltration was seen. All experimental groups showed no biochemical evidence for hyperglycemia probably due to the mild destruction of a small number of B cells. The results indicate that NSP might possess a restorative action on insulitis induced by multiple low dose streptozotocin administration in mice.
Cell Mol Biol 1991
PMID:Morphological changes in the endocrine pancreas of mice after treatment with streptozotocin combined with cyclophosphamide and neurotropin. 183 58

Analysis of glucose transporter mRNA levels in adipose tissue from streptozotocin (STZ)-induced diabetic rats demonstrated a specific decrease (10-fold) in adipose tissue GLUT-4 mRNA with no significant effect on GLUT-1 mRNA levels. Treatment of STZ-diabetic rats with twice daily injections of insulin for 1-3 days resulted in a 16-fold increase in the relative amount of GLUT-4 mRNA to levels approximately 2-fold greater than those in control animals. However, after 7 days of insulin therapy the amount of GLUT-4 mRNA decreased approximately 2-fold back to the levels in the control animals. Normalization of the STZ-induced serum hyperglycemia by phlorizin treatment, which inhibits renal tubular reabsorption of glucose, had no effect on GLUT-4 mRNA in the absence of insulin. Similar to STZ-diabetes, fasting for 48 h also reduced adipose GLUT-4 mRNA levels. Parenteral administration of insulin with glucose over 7.5 h, but not glucose alone, increased the levels of the GLUT-4 mRNA 3- to 4-fold. These studies demonstrate that the relative glycemic state does not influence GLUT-4 glucose transporter mRNA expression in vivo and strongly suggests that insulin is a major factor regulating the levels of GLUT-4 mRNA in adipose tissue.
Mol Endocrinol 1990 Apr
PMID:Regulation of glucose transporter messenger RNA levels in rat adipose tissue by insulin. 214 65

Transgenic mice expressing an insulin-promoted H-ras hybrid gene in pancreatic beta cells developed beta-cell degeneration and diabetes. The disease was manifested in male mice by hyperglycemia, glycosuria, and reduced plasma insulin levels, which appeared around 5 months of age and led to premature death. Histological analyses revealed large holes within the islets of Langerhans and a reduced number of beta cells. The destruction of the islets was not associated with an obvious inflammatory activity. Ultrastructural analysis showed extensive engorgement in the endoplasmic reticulum of the residual beta cells from diabetic males. The females carrying the insulin-promoted ras gene did not manifest any of the physiological abnormalities observed in males and showed only minor histological and ultrastructural changes, even at much greater ages.
Mol Cell Biol 1990 Apr
PMID:Diabetes induced in male transgenic mice by expression of human H-ras oncoprotein in pancreatic beta cells. 218 Dec 84

During the reductive process in the tissues, the aerobes generate a number of oxidants. Unless these oxidants are reduced, oxidative damage and cell death would occur. Oxidation of plasma membrane lipids leads to autocatalytic chain reactions which eventually alter the permeability of the cell. The role of oxidative damage in the pathophysiology of diabetic complications and ischemic reperfusion injury of myocardium, especially the changes in the channel activity which may lead to arrhythmia have been studied. Hyperglycemia activates aldose reductase which could efficiently reduce glucose to sorbitol in the presence of NADPH. Since NADPH is also aldose required by glutathione reductase for reducing oxidants, its diversion would lead to membrane lipid oxidation and permeability changes which are probably responsible for diabetic complications such as cataractogenesis, retinopathy, neuropathy etc. Antioxidants such as butylated hydroxy toluene (BHT) and also reductase inhibitors prevent or delay some of these complications. By using patch-clamp technique in isolated frog myocytes, we have shown that hydroxy radicals generated by ferrous sulfate and ascorbate as well as lipid peroxides such as t-butyl hydroperoxide facilitate the entry of Na+ by oxidizing Na+-channels. Increased intracellular Na+ leads to an increase in Na+/Ca2+ exchange. The increased Na+ concentration by itself may produce electrical disturbance which would result in arrhythmia. Increased Ca2+ may affect proteases and may help in the conversion of xanthine dehydrogenase to xanthine oxidase, consequently increased production of super oxide radicals. Increased membrane lipid peroxidation and other oxygen free-radical associated membrane damage in myocytes has been demonstrated.
Mol Cell Biochem
PMID:The effect of oxidants on biomembranes and cellular metabolism. 251 41

Eighteen timed-pregnant Syrian golden hamsters were injected subcutaneously with streptozotocin (STZ, 60 mg/kg bw) early on gestational day 10. The response varied widely, and based on changes in blood glucose levels during gestational days 11 to 15, the hamsters were categorized into four groups: 1) no change; 2) mild diabetes (200-250 mg/dl), which reverted; 3) moderate diabetes (greater than 300 mg/dl), which reverted; and 4) moderate to severe diabetes (300-500 mg/dl), which was sustained. Two hours before sacrifice, a 25 mg tablet of bromodeoxyuridine (BrdU) was implanted subcutaneously into each experimental hamster and into 17 control pregnant hamsters that had not received STZ. BrdU-labelling was demonstrated immunochemically in the pancreatic islet cells. In control hamsters, the mean labelling index (LI) of the islet cells was 0.07% and did not exceed 0.2% in any hamster. Following injection of STZ, islet cell LI's remained low (0.13%) if the blood glucose levels were not altered by the diabetogenic drug. However, LI's were increased in islet cells of hamsters which showed a mild to moderate diabetes which rapidly reverted; the highest LI's (5% +/- 2.1) occurred in four hamsters that were killed 2 days after receiving STZ. The LI's were moderately increased (1.4% +/- 0.42) in two hamsters with moderate diabetes killed 2 days after STZ, but LI's were low (0.12% +/- 0.04) in six hamsters with moderate to severe diabetes killed 3, 4, and 5 days after STZ. Reversion of hyperglycemia to normoglycemia correlated closely with increased DNA synthesis in the islet cells of the pregnant hamsters. These observations strongly suggest that following mild cytotoxic injury induced by STZ, the B cells regenerated and insulin production was restored sufficiently to maintain normoglycemia.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Correlations between blood glucose levels and bromodeoxyuridine labelling indices of pancreatic islet cells following streptozotocin administration to pregnant Syrian golden hamsters. 256 82

Protection by thymosin fraction 5 (TF5) from subdiabetogenic-dose streptozotocin (STZ)-induced type I diabetes in CD-1 mice was investigated. Mice which received multiple subdiabetogenic-dose (35 mg/kg) injections of STZ became hyperglycemia within two weeks. Hyperglycemia was also induced in those treated with low dose of TF5 (0.01 mg/day) in addition to STZ, though it was somewhat mild. In contrast, animals given STZ plus high dose of TF5 (0.1 mg/day) remained normoglycemic throughout the whole observation period (within 4 weeks). In the pancreatic islets from these animals, histologically, the well-granulated beta cells were observed and the infiltration of lymphoid cells was absent or mild. These results suggest that the administration of TF5 prevents the induction of insulitis and hyperglycemia in the subdiabetogenic-dose STZ-treated mice.
Cell Mol Biol 1989
PMID:Protection by thymosin fraction 5 from streptozotocin-induced diabetes in mice. 265 87


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