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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well accepted that diabetes leads to learning and memory impairment in humans and rodents. Because central delta-opioid receptors have important roles in learning processes, we investigated the involvement of delta-opioid receptors in the spatial learning impairment in streptozotocin (STZ)-induced diabetic mice by the Morris water maze test. The escape latencies to the platform were significantly increased in diabetic mice without changes in the ability to swim. The delta1/delta2-opioid receptor antagonist naltrindole (1 mg/kg/day, s.c.) slightly, but not significantly, reduced the escape latencies in diabetic mice. The selective delta1-opioid receptor antagonist 7-benzylidenenaltrexone (0.3 and 1 mg/kg/day, s.c.), but not the selective delta2-opioid receptor antagonist naltriben (0.3 and 1 mg/kg/day, s.c.), significantly reduced the escape latencies in diabetic mice. These antagonists had no effect on the escape latencies in non-diabetic mice. The selective delta1-opioid receptor agonist [D-Pen2, D-Pen5]-enkephalin (10 nmol/mouse/day, i.c.v.) significantly increased the escape latencies in both non-diabetic and diabetic mice. Based on these results, we suggest that the enhanced response to central delta1-opioid receptors in diabetic mice is involved, at least in part, in the spatial learning impairment in the Morris water maze test.
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PMID:Involvement of delta1-opioid receptors in the spatial learning impairment in streptozotocin-induced diabetic mice. 1631 98

Clinical and experimental studies have been reported that antidepressant drugs can be used as co-analgesics in the management of neuropathic pain. However, the mechanism through which they alleviate pain still remains unclear. The aim of the present study was to investigate the possible mechanism of action of fluoxetine-induced antinociceptive effect in streptozotocin-induced diabetic mice, especially the involvement of non-serotonergic neurotransmitters and their receptors. Diabetes was induced in male Laka mice with a single intraperitoneal injection of streptozotocin (200 mg/kg). Four weeks after streptozotocin, diabetic mice were tested for pain responses in the tail-immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia as compared with control mice. Fluoxetine (10 and 20 mg/kg, i.p) injected into diabetic mice produced an antinociceptive effect in both tail-immersion and hot-plate assays. The antinociceptive effect of fluoxetine in diabetic mice was significantly lower as compared with that in control mice. Pretreatment with a muscarinic receptor antagonist, atropine (2 and 5 mg/kg, i.p) and an opioid receptor antagonist, naloxone (2 and 5 mg/kg, i.p), but not the alpha(2)-adrenoreceptor antagonist, yohimbine (2 and 5 mg/kg, i.p) reversed the antinociceptive effect of fluoxetine (20 mg/kg). These results suggest that apart from serotonin pathway, muscarinic and opioid receptors also participate in fluoxetine-induced antinociception in diabetic neuropathic pain.
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PMID:Possible involvement of cholinergic and opioid receptor mechanisms in fluoxetine mediated antinociception response in streptozotocin-induced diabetic mice. 1665 Apr 2

To assess whether diabetes alters the regulatory effects of mu-opioid receptor (MOR) agonists on the cholinergic bronchoconstriction, we investigated the inhibitory effects of endomorphins (EMs) on the electrical field stimulation (EFS)-induced cholinergic bronchoconstriction in type 1 diabetic rats. At 4 weeks after the onset of diabetes, both the EFS- and exogenous acetylcholine (ACh)-induced bronchoconstriction in diabetes in vitro were greater than those in non-diabetes rats. Furthermore, endomorphin 1 (EM1) and endomorphin 2 (EM2) inhibited the response to EFS in diabetic rat isolated bronchus in a concentration- and frequency-dependent manner, which is in agreement with that in non-diabetes. However, the inhibitory effects of EMs on the EFS-induced bronchoconstriction in diabetes were significantly weaker than those in non-diabetes. Both EM1 and EM2 (1 microM) had no effect on the contractile response to exogenous ACh, indicating a prejunctional effect. Furthermore, the inhibitory effect on the EFS-induced bronchoconstriction was blocked by naloxone (10 microM). Eight weeks after the induction of diabetes, both the EFS- and exogenous ACh-induced bronchoconstrictions in diabetes were further enhanced compared to those in short-time (4 weeks) diabetic rats. Moreover, the inhibitory effects of EMs on the EFS-induced bronchoconstriction were further attenuated. These results suggest that dysfunction of presynaptic inhibitory modulation through opioid receptor by EMs may take place in the bronchus of diabetic rats.
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PMID:Abnormal modulation of cholinergic neurotransmission by endomorphin 1 and endomorphin 2 in isolated bronchus of type 1 diabetic rats. 1690 87

Few Type 2 diabetes loci are considered confirmed and replicated across multiple populations. Some genes that have become accepted as contributors to diabetes risk include: calpain 10, peroxisome proliferator-activated receptor-gamma, ATP-sensitive inwardly rectifying potassium channel subunit Kir6.2, hepatocyte nuclear factor 4alpha and hepatic transcription factor 1. While numerous reports of new diabetes loci enter the literature on a regular basis, this review focuses on selected novel associations reported within the last 12 months. In particular, we highlight recent reports of associations between Type 2 diabetes and the transcription factor 7-like 2 gene, associations with micro-opioid receptor and supressor of cytokine signaling 2 genes, and expression and functional analyses of adipokines vaspin and retinol binding protein 4. These new results provide insights into possible mechanisms influencing disease susceptibility and thus new diagnostic and therapeutic opportunities for Type 2 diabetes.
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PMID:Genetic contributions to type 2 diabetes: recent insights. 1733 Oct 67

The purpose of this study was to assess the antinociceptive and antiallodynic effect of melatonin as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral administration of melatonin (10-300 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. In addition, K-185 (a melatonin MT(2) receptor antagonist, 0.2-2 mg/kg, s.c.) completely blocked the melatonin-induced antinociception in diabetic rats, whereas that naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) and naltrindole (a selective delta opioid receptor antagonist, 0.5 mg/kg, s.c.), but not 5'-guanidinonaltrindole (a selective kappa opioid receptor antagonist, 1 mg/kg, s.c.), partially reduced the antinociceptive effect of melatonin. Given alone K-185, naltrexone, naltrindole or 5'-guanidinonaltrindole did not modify formalin-induced nociception in diabetic rats. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of melatonin (75-300 mg/kg) dose-dependently reduced tactile allodynia in diabetic rats. Both antinociceptive and antiallodynic effects were not related to motor changes as melatonin did not modify number of falls in the rotarod test. Results indicate that melatonin is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that melatonin MT(2) and delta opioid receptors may play an important role in these effects.
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PMID:Melatonin reduces formalin-induced nociception and tactile allodynia in diabetic rats. 1792 May 85

Our previous studies have shown that endomorphins (EMs), endogenous ligands for mu-opioid receptor, display a significant potentiation effect on mouse colonic motility. In the present study, to assess whether diabetes alters these modulatory effects of EMs on colonic motility, we investigated the effects of EMs in type 1 diabetic mouse colon in vitro. At 4 weeks after the onset of diabetes, carbachol-induced contractions in the longitudinal muscle of distal colon were significantly reduced compared to those of non-diabetic mice. Furthermore, the contractile effects induced by EMs in the longitudinal muscle of distal colon and in the circular muscle of proximal colon were also significantly reduced by type 1 diabetes. It is noteworthy that EMs-induced longitudinal muscle contractions were not significantly affected by atropine, Nomega-nitro-l-arginine methylester (l-NAME), phentolamine, propranolol, hexamethonium, methysergide and naltrindole. On the other hand, tetrodotoxin, indomethacin, naloxone, beta-funaltrexamine, naloxonazine and nor-binaltorphimine completely abolished these effects. These mechanisms responsible for EMs-induced modulatory effects in type 1 diabetes were in good agreement with those of non-diabetes, indicating similar mechanisms in both diabetes and non-diabetes. At 8 weeks after the onset of diabetes, both carbachol- and EMs-induced longitudinal muscle contractions were similar to those of short-time (4 weeks) diabetic mice. In summary, all the results indicated that type 1 diabetes significantly attenuated the modulatory effects of EMs on the mouse colonic motility, but the mechanisms responsible for these effects were not significantly altered.
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PMID:Type 1 diabetes attenuates the modulatory effects of endomorphins on mouse colonic motility. 1802 65

The purpose of this study was to assess the antinociceptive and antiallodynic effect of pyritinol as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral acute administration of pyritinol (50-200 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. Moreover, prolonged administration of pyritinol (12.5-50 mg/kg, every 2 days for 2 weeks) reduced formalin-induced nociception. 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) or indomethacin (a non-selective cycloxygenase inhibitor, 5 mg/kg, i.p.), blocked the pyritinol-induced antinociception in diabetic rats. Given alone ODQ, naltrexone or indomethacin did not modify formalin-induced nociception in diabetic rats. Oral acute (200 mg/kg) or prolonged (25 mg/kg, every 2 days for 2 weeks) administration of pyritinol significantly reduced streptozotocin-induced changes in free carbonyls, dityrosine, malondialdehyde and advanced oxidative protein products. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of pyritinol (50-200 mg/kg) reduced tactile allodynia in diabetic rats. Results indicate that pyritinol is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that activation of guanylyl cyclase and the scavenger properties of pyritinol, but not improvement in glucose levels, play an important role in these effects.
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PMID:Pyritinol reduces nociception and oxidative stress in diabetic rats. 1859 82

Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of beta cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a mu-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40 mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10 mg/kg/day subcutaneously) for 24 days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1beta, tumor necrosis factor-alpha and interferon-gamma] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of beta cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction of beta cells and insulitis in the MLDS model of type 1 diabetes.
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PMID:Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice. 1867 92

In addition to producing analgesia, opioids have also been proposed to regulate glucose homeostasis by altering insulin secretion. A considerable controversy exists, however, regarding the contribution of the mu-opioid receptor (MOR-1) to insulin secretion dynamics. We employed congenic C57BL/6J MOR-1 knockout (KO) mice to clarify the role of MOR in glucose homeostasis. We first found that both sexes of MOR-1 KO mice weigh more than wild-type mice throughout postnatal life and that this increase includes preferentially increased fat deposition. We also found that MOR-1 KO mice exhibit enhanced glucose tolerance that results from insulin hypersecretion that reflects increased beta-cell mass and increased secretory dynamics in the MOR-1 mutant mice compared with wild type. Analysis of the isolated islets indicated that islet insulin hypersecretion is mediated directly by MOR expressed on islet cells via a mechanism downstream of ATP-sensitive K(+) channel activation by glucose. These findings indicate that MOR-1 regulates body weight by a mechanism that involves insulin secretion and thus may represent a novel target for new diabetes therapies.
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PMID:The MOR-1 opioid receptor regulates glucose homeostasis by modulating insulin secretion. 1922 Oct 53

Pruritus is a common complication of end-stage renal disease (ESRD), affecting about one-third of dialysis patients. It is a chronic, unpleasant symptom with a strong negative impact on patients' quality of life, often inducing sleeplessness and mood disorders. Recent data show that it is also associated with increased mortality. The pathogenesis of uraemic pruritus (UP) is multifactorial. Triggering factors may include uraemia-related abnormalities (particularly involving calcium, phosphorus and parathyroid hormone metabolism), accumulation of uraemic toxins, systemic inflammation, cutaneous xerosis, and common co-morbidities such as diabetes mellitus and viral hepatitis. Recent findings suggest that the neurophysiology of itch is similar to that of pain; this has led to the hypothesis that the two phenomena also closely interact in ESRD patients, who often also experience uraemic neuropathy. The management of UP needs to address several different issues, such as optimization of dialysis efficacy and skin hydration, and correction of calcium-phosphorus metabolism abnormalities. A wide range of antipruritic drugs have been suggested for the treatment of UP, although most of them have only been tested in small, uncontrolled trials, which have yielded conflicting results. Antihistamines are now known to have little or no efficacy, although they are still often prescribed. Novel neurotropic drugs such as gabapentin, along with opioid receptor modulators such as nalfurafine, appear to be effective and well tolerated, but their efficacy has not yet been directly compared. Finally, physical therapies, including UV radiation, may also have a role in patients with refractory symptoms.
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PMID:Uraemic pruritus: clinical characteristics, pathophysiology and treatment. 1927 70


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