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)

The focal microflora of pyo-inflammatory processes has been studied in dynamics in 200 patients with diabetes mellitus. It was found that a longer and more severe course was due to the changed specific composition of causative agents and to the increased specific diversity of the latter in the process of pyo-inflammatory progressing. It was established that the usage of the method of "close" wound management with the application of oxytocin inhibited the change of the causative agents in the course of the disease, led to a more rapid elimination of microorganisms from the pyo-inflammatory focus, to the less frequency of recurrent surgical interventions and shorter duration of courses of treatment in contrast to the results obtained with the other methods of treatment.
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PMID:[Microbiological specifics in the course of suppurative inflammatory processes in soft tissues of patients with diabetes mellitus]. 1190 22

The central mechanisms underlying diabetes-associated impotence are currently unknown. This study utilized immunolesion techniques to eliminate hindbrain catecholaminergic projections to the medial hypothalamus which have been reported to be glucoresponsive. The immunolesioned male rats had an attenuated feeding response to glucoprivic challenge. Furthermore, these lesioned rats had significantly attenuated penile reflexes. Northern blot analyses of hypothalamic oxytocin mRNA expression showed a significant increase; however, neuropeptide Y mRNA expression did not. These results suggest that hindbrain catecholaminergic neurones may alter the expression of hypothalamic neuropeptides that stimulate penile erections based upon glucoregulatory signals from the periphery.
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PMID:Immunolesion of hindbrain catecholaminergic projections to the medial hypothalamus attenuates penile reflexive erections and alters hypothalamic peptide mRNA. 1200 May 38

MAP (mitogen-activated protein) kinase (also called Erk 1/2) plays a crucial role in cell proliferation and differentiation. Its impact on secretory events is less well established. The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. All further experiments were performed using 2.5 min incubations. The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. The data indicate that MAP kinase is active and under the control of MAP kinase. PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells.
Int J Exp Diabetes Res 2001
PMID:Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. 1236 12

Shoulder dystocia is an unpredictable obstetric complication with the incidence of 0.15% to 2%. An increase in the incidence of shoulder dystocia has been recorded over the last 20 years, probably just because it has now been regularly registered at maternity wards as an obstetric complication. The risk factors for shoulder dystocia include fetal macrosomia, fetal malformations and tumors, maternal adiposity, excessive weight gain during pregnancy, diabetes mellitus, pathologic pelvis, multiparity, short maternal stature, advanced maternal age, postterm pregnancy, so-called midforceps delivery or vacuum extraction, prolonged delivery stage II, oxytocin labor induction, premature fetal expression according to Kristeller, and previous shoulder dystocia in macrosomatic children. The sequels of shoulder dystocia and obstetric maneuvers for incarcerated shoulder release include clavicular fracture, brachial plexus lesions, sternocleidomastoid muscle distension with or without hematoma, diaphragmatic paralysis, Horner's syndrome, peripartal asphyxia and consequential cerebral lesions (cerebral palsy), and peripartal death. Maternal complications due to shoulder dystocia are postpartal hemorrhage, cervical and vaginal lacerations, frequent infections during the puerperium, symphysiolysis and rupture of the uterus, and secondary cesarean section with related complications due to unsuccessful obstetric procedures or as continuation of Zavanelli's maneuver. McRoberts' maneuver (or Gaskin maneuver) is recommended as the initial procedure for shoulder release in case of shoulder dystocia. If it fails, other obstetric procedures such as Resnik's suprapubic pressure and Woods' grip with posteriorly placed arm release should be used, always with gross lateral episiotomy. The performance of all these obstetric procedures requires skilfull and highly experienced obstetrician and obstetric team as a whole.
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PMID:Fetal shoulder dystocia. 1259 26

In twin pregnancies, the use of beta-adrenergics is associated with a significantly higher incidence of cardiovascular complications, and calcium channel blockers as well as oxytocin antagonists currently appear as first line agents. After extreme preterm delivery of the first twin and in selected patients, the birth of second twin may be delayed with a mean gain of 10-50 days. In cases of symptomatic placenta previa with mild-to-moderate bleeding, tocolytic agents may be associated with a prolongation of pregnancy and increased birth weight without significant impact on frequency or severity of bleeding. Calcium channel blockers are the drugs of choice in the event of diabetes. Indomethacin is a potent tocolytic, in particular in patients with polyhydramnios. However, it may cause oligohydramnios, premature closure of the ductus arteriosus and intrauterine fetal death when high doses are administered for a duration exceeding 48 to 72 hours, particularly beyond 32 weeks' gestation. The neonatal complications of indomethacin occur frequently. Tocolysis appears to reduce the failure rate of external cephalic version at term.
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PMID:[The therapeutic role of tocolysis]. 1496 18

The hyperosmolality associated with diabetes mellitus triggers an increase in neuronal activity and vasopressin production within magnocellular neurosecretory cells (MNCs) of the hypothalamic supraoptic nucleus (SON). In this study, we examined the effect of chronic diabetes on the function and survival of these neurons. After 6 months, but not 6 weeks, of streptozotocin (STZ)-induced diabetes, we observed an increase in the appearance of small hyperchromatic neurons and a decrease in SON neuronal density. A subpopulation of neurons within the SON at this time point demonstrated positive staining for cleaved caspase-3 and TUNEL, two markers of apoptosis. In addition, the number of vasopressin-positive neurons was decreased. Markers for apoptosis did not colocalize with vasopressin immunopositivity; this was probably due to a diabetes-induced degenerative process causing downregulation of vasopressin expression or depletion of neuropeptide. Although the phenotypes of the apoptotic neurons were not identified, other SON neurons including oxytocin-producing neurons are unlikely to be affected by chronic hyperglycemia. Microglial hypertrophy and condensation were also observed in the 6-month diabetic SON. Although upregulation of vasopressin production in response to acute hyperosmolality is adaptive, prolonged overstimulation of vasopressin-producing neurons in chronic diabetes results in neurodegeneration and apoptosis.
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PMID:Apoptosis of vasopressinergic hypothalamic neurons in chronic diabetes mellitus. 1500 92

The aim of our in vitro experiments was to study the role of oxytocin (OT), cAMP/protein kinase A (PKA), and mitogen-activated protein kinase (ERKs MAP-kinase) in the control of ovarian cell functions as well as the role of PKA and MAPK in mediating OT effects on these processes. The whole porcine ovarian follicles were cultured in the presence or absence of OT (1, 10, 100 ng/ml), PKA inhibitor Rp-cAMPS (10 nM), MAP-kinase inhibitor PD98059 (1 microg/ml), or their combination. The release of prostaglandins F (PGF) and E (PGE) were determined by RIA, PKA (alpha-cat subunit), the proliferation-associated peptide PCNA and ERK-1, -2 expression in cell lyzates were analysed by Western-blotting. OT stimulated the release of PGF and PGE, and accumulation of PKA, ERK-1/-2, and PCNA in cell lysate. PD98059 decreased the basal PGF and PGE output, as well as reduced both ERK-1 and ERK-2 accumulation in cell lysates. Rp-cAMPS decreased PKA accumulation in cell lysates. Rp-cAMPS prevented the OT-induced stimulation of PKA, ERK-1, ERK-2, PGF, and PGE, PD98059 did so for PKA, PGF, and PGE. However, PD98059 reduced either basal or OT-induced p-ERK level. OT-stimulated PCNA accumulation was only slightly modified by these blockers. These observations suggest that OT, PKA, and ERKs MAPK can be involved in the control of PGs release and proliferation of ovarian cells. The influence of OT on both PKA and MAPK, and the ability of PKA and MAPK blockers to prevent completely or partially OT effects suggest, that effects of OT on PGF and PGE can be mediated by both PKA and MAPK. The role of MAPK and PKA in mediating the proliferative effects of OT seems to be minor assuming the involvement of other intracellular messengers.
Exp Clin Endocrinol Diabetes 2004 Feb
PMID:The role of oxytocin, protein kinase A, and ERK-related MAP-kinase in the control of porcine ovarian follicle functions. 1503 77

Acid (aspartyl), basic (arginyl) and neutral (alanyl) aminopeptidases degrade angiotensins, vasopressin, oxytocin, bradykinin and enkephalins. These peptides regulate memory, energy homeostasis, water-salt balance and blood pressure, functions that are mainly exerted in the hippocampus and hypothalamus, and that can be affected by diabetes mellitus. To evaluate the relationship between the diabetes mellitus and processing and inactivation roles of these representative aminopeptidases, we measured their activities in both brain structures of control and streptozotocin-diabetic rats. Hypothalamic soluble aspartyl and arginyl aminopeptidases presented significant decreased activity levels in diabetic rats, which were mitigated by insulin therapy. In addition to membrane-bound puromycin sensitive and insensitive alanyl aminopeptidases, its soluble puromycin sensitive form did not differ between diabetic and control rats in both brain structures. Glucose and/or insulin did not seem to alter in vitro the hypothalamic activities of soluble aspartyl and arginyl aminopeptidases. The implied hypothalamic control of regulatory peptide activity by aspartyl and arginyl aminopeptidases supports the hypothesis that the hydrolytic ability of these enzyme types could be a common link for the disruptions of water-salt balance, blood pressure and energy homeostasis in diabetes mellitus.
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PMID:Aspartyl, arginyl and alanyl aminopeptidase activities in the hippocampus and hypothalamus of streptozotocin-induced diabetic rats. 1769 97

Type 1 diabetes (T1D) is linked to an 'encephalopathy' explained by some features common to the aging process, degenerative and functional disorders of the central nervous system. In the present study we describe a manifest hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in two different experimental mouse models of T1D including the pharmacological one induced by streptozotocin and the spontaneous NOD (nonobese diabetic mice). The high expression of hypothalamic hormones like oxytocin and vasopressin were part to this alteration, together with elevated adrenal glucocorticoids and prominent susceptibility to stress. In the hippocampus of diabetic animals a marked astrogliosis, often associated with neural damage, was present. Dentate gyrus neurogenesis was also affected by the disease: proliferation and differentiation measured by bromodeoxyuridine immunodetection were significantly reduced in both experimental models used. Several facts, including changes associated with chronic hyperglycemia, hyperstimulation of the HPA axis, increased levels of circulating glucocorticoids in combination with brain inflammation and low production of new neurons, contribute to emphasize the impact of diabetes on the central nervous system.
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PMID:Brain alterations in autoimmune and pharmacological models of diabetes mellitus: focus on hypothalamic-pituitary-adrenocortical axis disturbances. 1866 1

Delivery of viable young requires co-ordination of fetal maturation with the onset of labour at term. In turn, this depends on a cascade of fetal and maternal endocrine events. The sequence of these events is broadly similar in most mammals but there are differences in placental hormone synthesis and in the timing and magnitude of key prepartum endocrine changes between species. In most farm animals, maternal progesterone (P4) levels decline and oestrogen levels increase in the last 5 - 10 days before delivery in response to activation of the fetal hypothalamicpituitary-adrenal (HPA) axis and increased fetal cortisol concentrations. This cortisol surge is also responsible for fetal maturation and increasing uteroplacental prostaglandin (PG) synthesis. In the mare, there is little, if any, P4 in the maternal plasma during late gestation and both progestagens and oestrogens are produced by a feto-placental unit which uses precursors supplied by the fetus to synthesise a range of C21 and C18 steroids, many of which are unique to the horse. Regulation of uterine quiescence and activation is, therefore, complex in the mare near term. Indeed, total progestagen concentrations rise and total oestrogen levels fall in the mare during the last 20 - 30 days of gestation and only show the changes typical of impending parturition in other species in the last 24 - 48 h before delivery. Fetal cortisol concentrations also rise late in gestation in the horse compared to other species. In common with other species, the prepartum endocrine cascade appears to begin in the fetal horse with activation of the fetal HPA axis but, initially, the primary product of the fetal equine adrenal appears to be pregnenolone (P5) and not cortisol. This leads to increased progestagen production by the uteroplacental tissues, which maintains uterine quiescence in the face of increasing uterine stretch caused by the rapidly growing fetus. Very close to term in association with increasing fetal ACTH levels, the fetal equine adrenals appear to switch to producing cortisol. This late cortisol surge induces a period of rapid fetal maturation and may also contribute to increased uteroplacental oestradiol-17 beta and PG production. The fall in P5 availability may reduce uteroplacental progestagen production and lift the block on myometrial contractility. Finally, increased PG secretion activates myometrial contractions, which stimulate oxytocin release via a neuroendocrine reflex. The endocrine regulation of equine parturition, therefore, involves progestagens, oestrogens, PGs and oxytocin as in other species. However, further studies are required to establish the causes and consequences of the rise and fall in maternal progestagens and the extent to which initiation of equine labour depends on the fetal HPA axis.
Exp Clin Endocrinol Diabetes 2008 Jul
PMID:The Endocrinology of equine parturition. 1870 35


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