Effect In Diabetic Mice Research Articles

Anti-hyperglycemic, antioxidant and anti-inflammatory effects of VIP and a VPAC1 agonist on streptozotocin-induced diabetic mice

Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide with potent anti-inflammatory properties, and its receptor, VPAC1, mediates most of the anti-inflammatory effects of VIP. Diabetes mellitus is characterized by increased oxidation and inflammation due to persistent hyperglycemia. This research was performed to investigate the effects of VIP and a VPAC1 agonist on streptozotocin (STZ)-induced type 1 diabetic mice. Intraperitoneal injection of VIP and VPAC1 agonist (50 nmol/kg/day in saline) over a 28-day period (1) decreased food intake, (2) increased body weight, (3) improved visceral index, (4) increased the fasting plasma insulin levels, (5) decreased the fasting plasma glucose, (6) improved the glucose tolerance, (7) decreased pancreas H 2O 2 and malondialdehyde (MDA) and (8) increased total antioxidant activity (T-AOC) in the liver, spleen and pancreas. The results of histopathological and immunohistochemical analysis showed that VIP and the VPAC1 agonist improved the structure and cellularity of islets and ameliorated the insulin-secreting activity of islets. Additionally, administration of VIP or the VPAC1 agonist not only significantly decreased the plasma TNFα and CRP and promoted IL-10 in diabetic mice but also blocked the increased NF-κB activity of pancreatic tissue in diabetic mice. Furthermore, the VPAC1 agonist displayed stronger effects than VIP. These results show that both VIP and VPAC1 agonist ameliorated STZ-induced diabetes and protected mice against oxidative stress and inflammation associated diabetes, with VPAC1 being the receptor most responsible for these positive effects in diabetic mice.

The Wound Healing Effect of Hydnocarpi Semen Extract on Ulcer in Diabetic Mice

The extract from Hydnocarpi Semen (HS) has been used to treat leprosy and its anti-inflammatory activity has been reported. However, the effect of HS on the treatment of diabetic or peripheral ulcer is not well known. We therefore examined its wound healing effects on ulcer area in diabetic mice. GC and GC/MS analysis with the total extract of HS show that the main constituents of the extract are chaulmoogric acid, hydnocarpic acid, and gorlic acid. Whereas HS showed wound healing effect in diabetic ulcer, there was no hypoglycemic effect in diabetic mice. The treatment of HS extract significantly decreased the level of total WBC and neutrophils in mice compared to control mice. Cutting ulcer was induced by the round-shaped punch on the backside of diabetic mice and the extract of HS was given orally or topically. The wound area score significantly decreased after treatment of HS at dose of 50 mg/kg. The treatment of HS also induced the activation of macrophages and increased the production of IL-12 and TNF- in macrophages, indicating that the wound healing by HS extract is associated with the inflammatory effect via the activation of macrophages. Our results suggest that HS extract can be a new therapeutic candidate for treatment of diabetic ulcer.

Effect of astragaloside IV on hepatic glucose‐regulating enzymes in diabetic mice induced by a high‐fat diet and streptozotocin

Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) are important in control of blood glucose homeostasis, and are considered to be potential targets for antidiabetic drugs. Astragaloside IV has been reported to have a hypoglycemic effect. However, the biochemical mechanisms by which astragaloside IV regulates hepatic glucose-metabolizing enzymes remain unknown. The present study examines whether GP and G6Pase mediate the hypoglycemic effect of astragaloside IV. Type 2 diabetic mice were treated with astragaloside IV for 2 weeks. Blood glucose and insulin levels were measured by a glucometer and the ELISA method, respectively. Total cholesterol (TC) and triglyceride (TG) levels were determined using Labassay kits. Activities of hepatic GP and G6Pase were measured by the glucose-6-phosphate dehydrogenase-coupled reaction. The mRNA and protein levels of both enzymes were determined by real-time RT-PCR and Western blotting. Astragaloside IV at 25 and 50 mg/kg significally decreased the blood glucose, TG and insulin levels, and inhibited the mRNA and protein expression as well as enzyme activity of GP and G6Pase in diabetic mice. Astragaloside IV exhibited a hypoglycemic effect in diabetic mice. The hypoglycemic effect of this compound may be explained, in part, by its inhibition of hepatic GP and G6Pase activities.

Role of α 2-adrenoceptors in enhancement of antinociceptive effect in diabetic mice

The present studies investigated behavioral and neurochemical aspects of the noradrenergic and serotonergic nervous systems in streptozotocin-induced diabetic mice. We previously reported that intrathecal (i.t.) injection of norepinephrine significantly potentiated antinociception in diabetic mice compared to that in non-diabetic mice, and that antinociception due to norepinephrine injection was completely abolished by pretreatment with yohimbine, an α 2-adrenoceptor antagonist. The present studies demonstrated that i.t. injection of clonidine also showed more-potent antinociceptive activity in diabetic mice than in non-diabetic mice, but that i.t. methoxamine injection did not affect diabetic or non-diabetic mice. The antinociceptive potency due to i.t. injection of 5-HT was significantly lower in diabetic than in non-diabetic mice. In a neurochemical study, we found that the density of [ 3H]-rauwolscine binding sites in spinal α 2-adrenoceptors was significantly higher in diabetic than in non-diabetic mice, but that the binding affinity was unchanged. Spinal norepinephrine turnover was determined by measuring the decline in tissue norepinephrine concentration at 3 h after injection of the tyrosine hydroxylase inhibitor α-methyl- p-tyrosine. The spinal norepinephrine concentration decreased to 43.7% from the baseline in non-diabetic mice, while it was 21.0% in diabetic mice. These results suggest that, based on the decrease of norepinephrine release in the spinal cord, up-regulation of spinal α 2-adrenoceptors caused the increase of antinociception due to i.t. injection of an α 2-adrenoceptor agonist in streptozotocin-induced diabetic mice, and it seemed that the stimulation of α 2-adrenoceptors potentiated the antinociceptive effect. Thus, the spinal noradrenergic systems play an important moderating role in diabetes-induced neuropathic pain.

High-Mobility Group Box 1 Protein in Human and Murine Skin: Involvement in Wound Healing

High-mobility group box 1 (HMGB1) protein is a multifunctional cytokine involved in inflammatory responses and tissue repair. In this study, it was examined whether HMGB1 plays a role in skin wound repair both in normoglycemic and diabetic mice. HMGB1 was detected in the nucleus of skin cells, and accumulated in the cytoplasm of epidermal cells in the wounded skin. Diabetic human and mouse skin showed more reduced HMGB1 levels than their normoglycemic counterparts. Topical application of HMGB1 to the wounds of diabetic mice enhanced arteriole density, granulation tissue deposition, and accelerated wound healing. In contrast, HMGB1 had no effect in normoglycemic mouse skin wounds, where endogenous HMGB1 levels may be adequate for optimal wound closure. Accordingly, inhibition of endogenous HMGB1 impaired wound healing in normal mice but had no effect in diabetic mice. Finally, HMGB1 had a chemotactic effect on skin fibroblasts and keratinoyctes in vitro. In conclusion, lower HMGB1 levels in diabetic skin may play an important role in impaired wound healing and this defect may be overcome by the topical application of HMGB1.

HYPOGLYCEMIC EFFECT OF SEMIPURIFIED PEPTIDES FROM MOMORDICA CHARANTIA L. VAR. ABBREVIATA SER. IN ALLOXAN-INDUCED DIABETIC MICE

ABSTRACT Hypoglycemic effect of semipurified peptides from an aqueous extract of Momordica charantia L. var. abbreviata Ser. (MCV) in alloxan-induced diabetic mice was investigated. MC2-1, a semipurified peptide fraction from MCV produced a significant hypoglycemic effect in diabetic mice when compared to the diabetic control group. In a long-term study, mice were treated with MC2-1 and glibenclamide, respectively, once a day, for 28 days. Repeated oral administration of MC2-1 reduced significantly the fasting blood glucose level during the 28 days of treatment. Furthermore, MC2-1 significantly reduced hepatic malondialdehyde level, glycogen content, serum cholesterol, triglyceride and low-density lipoprotein cholesterol levels. At the same time, MC2-1 markedly increased high-density lipoprotein cholesterol and serum insulin levels after 28 days of treatment in diabetic mice. Loss in body weight was also prevented in diabetic mice. Hence, MC2-1 can be incorporated as a supplement in health-care food, drugs and/or combined with other hypoglycemic drugs. PRACTICAL APPLICATIONS The present study showed that peptide fraction MC2-1 obtained from an aqueous Momordica charantia L. var. abbreviata Ser. (MCV) extract has a strong hypoglycemic effect in alloxan-induced mice. MC2-1 administered at a dose of 20 mg/kg has a similar or even stronger hypoglycemic effect as that produced by the MCV aqueous extract administered at a dose of 500 mg/kg. The study revealed that MC2-1 is the main fraction with hypoglycemic effect in MCV aqueous extract. Through the removal of compounds with little or no hypoglycemic effect, the dosage needed for diabetes prevention and control is significantly reduced. At the same time, the compounds present in the aqueous extract, which could affect blood glucose level lowering effect, are minimized. MC2-1 can be added as supplement in health-care food, drugs or combined with other hypoglycemic drugs. In addition, the present study revealed the mechanism of action of the hypoglycemic fraction.

Effect of a number of protein extractors and protein isolated from the fruit of tomato plant Solanaceae at the level of glucose, fat, clotathione and melonadialdehyde in mice with diabetes

This study was included prepare a cold aqueous extract of solanaceae fruit plant. The study also comprised the isolation and study the proteinaceous compounds, seperated by using the gel filtration technique which was isolated two compound A (52251) Dalton and B (6725) Dalton . The effects of these extracts and compounds previously mentioned above were studied on serum glucose , total cholesterol , triglyceride (TG) , low density lipoprotein-cholesterol ( LDL-C ) and high density lipoprotein-cholesterol ( HDL-C ) levels , also glutathione ( GSH ) and malondialdehyde ( MDA ) levels in liver, kidney and heart tissues in diabetic mice- induced alloxan. Extracts were administerated interaperitioneally. After one week from the treatment the results were indicated that the crude aqueous non proteinaceous extract , proteinaceous precipitate and proteinaceous compounds ( A ) and ( B ) which were caused a significat decrease in serum glucose, total cholesterol , TG, LDL-C leves and MDA level in liver , kidney and heart tissues , with an associated significant increase in serum HDL-C level and GSH level in liver , kidney and heart tissues , in alloxan-induced diabetic mice. finally we suggest that most of extracts isolated from fruit plant ( especially compound B ) have anti-diabetic effect in diabetic mice.

Antidepressant-like effect of leptin in streptozotocin-induced diabetic mice

We previously reported that streptozotocin (STZ)-induced diabetic mice showed the depressive-like behavior in the tail suspension test. It has also been reported that leptin-deficient obese mice demonstrate the depressive-like behavior. Since STZ-induced diabetes causes a marked decrease in plasma leptin levels, it is possible that decrease in leptin levels and the depressive-like behavior may somehow be related. Therefore, we examined the effect of leptin on the depressive-like behavior of STZ-induced diabetic mice in the tail suspension test. The prolonged duration of immobility in diabetic mice was dose-dependently and significantly suppressed by single treatment with leptin (0.1–1 mg/kg, i.p.) without affecting on the locomotor activity. Leptin did not affect either the duration of immobility or the locomotor activity in non-diabetic mice. The anti-immobility effect of leptin (1 mg/kg, i.p.) in diabetic mice was significantly antagonized by the selective serotonin 2 (5-HT 2) receptor antagonist LY53,857 (0.03 mg/kg, s.c.), but not by the selective 5-HT 1A receptor antagonist WAY-100635 (0.03 mg/kg, s.c.). Antagonists administered alone did not affect either the duration of immobility or the locomotor activity in diabetic mice. In conclusion, we suggest that leptin exerts the antidepressant-like effect in diabetic mice mediated by, at least in part, 5-HT 2 receptors.

Endothelial Nitric Oxide Synthase–Dependent Tyrosine Nitration of Prostacyclin Synthase in Diabetes In Vivo

There is evidence that reactive nitrogen species are implicated in diabetic vascular complications, but their sources and targets remain largely unidentified. In the present study, we aimed to study the roles of endothelial nitric oxide synthase (eNOS) in diabetes. Exposure of isolated bovine coronary arteries to high glucose (30 mmol/l d-glucose) but not to osmotic control mannitol (30 mmol/l) switched angiotensin II-stimulated prostacyclin (PGI(2))-dependent relaxation into a persistent vasoconstriction that was sensitive to either indomethacin, a cyclooxygenase inhibitor, or SQ29548, a selective thromboxane receptor antagonist. In parallel, high glucose, but not mannitol, significantly increased superoxide and 3-nitrotyrosine in PGI(2) synthase (PGIS). Concurrent administration of polyethylene-glycolated superoxide dismutase (SOD), l-nitroarginine methyl ester, or sepiapterin not only reversed the effects of high glucose on both angiotensin II-induced relaxation and PGI(2) release but also abolished high-glucose-enhanced PGIS nitration, as well as its association with eNOS. Furthermore, diabetes significantly suppressed PGIS activity in parallel with increased superoxide and PGIS nitration in the aortas of diabetic C57BL6 mice but had less effect in diabetic mice either lacking eNOS or overexpressing human SOD (hSOD(+/+)), suggesting an eNOS-dependent PGIS nitration in vivo. We conclude that diabetes increases PGIS nitration in vivo, likely via dysfunctional eNOS.

Inhibitory effect of pine extract on α-glucosidase activity and postprandial hyperglycemia

Objective This study investigated the inhibitory effect of pine bark extract (PBE) and needle extract on carbohydrate-hydrolyzing enzymes and the hypoglycemic effect in diabetic mice ( Lep ob [ ob/ob]). Methods Pine bark and needle were dried and then placed in ethanol, and the extracts were assayed for the measurement of inhibition mode of PBE against α-amylase (EC 3.2.1.1) and α-glucosidase (EC 3.2.1.20). We also investigated the effect of long-term treatment with extracts on levels of postprandial blood glucose, body weight, food efficiency ratio, and gene expression of glucose transporter-4 in quadriceps muscle in diabetic mice ( Lep ob [ ob/ob]). Results The PBE showed competitive inhibition against salivary α-amylase and the combination of non-competitive and uncompetitive inhibition against yeast α-glucosidase. In animal experiments, PBE effectively suppressed the increase of postprandial blood glucose level by delaying absorption of diet, and body weights of the group that received PBE were significantly lower than that in the group administered 0.5% carboxylmethyl cellulose (control) 21 d after administration. Conclusions PBE can be used to suppress postprandial hyperglycemia of diabetic patients. It also can be applied for control of obesity by decreasing the food efficiency ratio, especially carbohydrates.

Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its antinociceptive effect

Diabetic neuropathic pain is one of the most commonly encountered neuropathic pain syndromes. However, the treatment of diabetic neuropathic pain is challenging because of partial effectiveness of currently available pain relievers. It is well known that diabetic animals are less sensitive to the analgesic effect of morphine, and opioids are found to be ineffective in the treatment of diabetic neuropathic pain. Cannabinoids are promising drugs and they share a similar pharmacological properties with opioids. It has been reported that cannabinoid analgesia remained intact and to be effective in some models of nerve injury. Thus, we investigated antinociceptive efficacy and the effects of cannabinoids on behavioral sign of diabetic neuropathic pain in diabetic mice by using WIN 55, 212-2, a cannabinoid receptor agonist. Diabetes was induced by streptozotocin (STZ) (200 mg/kg) and animals were tested between 45 and 60 days after onset of diabetes. Antinociception was assessed using the radiant tail-flick test. Mechanical and thermal sensitivities were measured by Von Frey filaments and hot-plate test, respectively. Tactile allodynia, but not thermal hyperalgesia developed in diabetic mice. Systemic WIN 55, 212-2 (1, 5 and 10 mg/kg) produced a dose-dependent antinociception both in diabetic and control mice. WIN 55, 212-2-induced antinociception were found to be similar in diabetic mice when compared to controls suggesting efficacy of cannabinoid antinociception was not diminished in diabetic mice. WIN 55, 212-2 also produced a dose-dependent antiallodynic effect in diabetic mice. This study suggests that cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain.

Hypoglycemic effects of aqueous extract of Rhizoma Polygonati Odorati in mice and rats

Water soluble extract of Rhizoma Polygonati Odorati (RPO) was studied for its hypoglycemic effect in diabetic mice and rats. Results showed that RPO significantly lowered hyperglycemia caused by starch loading in both normal and diabetic mice. Four week's administration with RPO reduced fasting blood glucose, decreased glycosylated hemoglobin (GHb), and improved the glucose tolerance in diabetic mice. In diabetic rats complicated with hyperlipemia, RPO prevented and reduced both hyperglycemia and hypertriglyceridemia. The results support the view that RPO may influence glucose or carbohydrate metabolism of diabetic animals in many ways including inhibiting the activity of α-glucosidase in digestive canal, and improving the metabolism of glucose and triglyceride.

Antinociceptive Effect of Gosha-jinki-gan, a Kampo Medicine, in Streptozotocin-Induced Diabetic Mice

We evaluated the antinociceptive effect of Gosha-jinki-gan, a Kampo medicine including processed Aconiti tuber, and its mechanism in streptozotocin-induced diabetic mice. Gosha-jinki-gan (0.1–1.0 g/kg, p.o.) showed a more potent antinociceptive effect in diabetic mice than in non-diabetic mice. The antinociceptive effect of Gosha-jinki-gan (0.3 g/kg, p.o.) in diabetic mice was inhibited by administration of either anti-dynorphin antiserum (5 μg, i.t.) or nor-binaltorphimine (10 mg/kg, s.c.), a κ-opioid antagonist. The antinociceptive activity of Gosha-jinki-gan (0.3, 1.0 g/kg, p.o.) was decreased by excluding processed Aconiti tuber. Furthermore, the antinociceptive effect of processed Aconiti tuber (0.03, 0.1 g/kg, p.o.) was also shown to be enhanced in diabetic mice. These results suggest that the increased antinociceptive effect of Gosha-jinki-gan in diabetic mice is partly derived from the action of processed Aconiti tuber and that it is based on stimulation of spinal κ-opioid receptors via dynorphin release. Gosha-jinki-gan was considered useful for treating painful diabetic neuropathy.

Effects of diabetes on methamphetamine-induced place preference in mice

The effects of diabetes on methamphetamine-induced place preference in mice were examined. Methamphetamine caused a dose-dependent place preference in both diabetic and non-diabetic mice. Methamphetamine preferentially induced place preference in diabetic mice as compared to those in non-diabetic mice. Indeed, methamphetamine-induced place preference at a dose of 0.3 mg/kg in diabetic mice was similar to that at 3 mg/kg in non-diabetic mice. Furthermore, methamphetamine-induced place preference in both diabetic and non-diabetic mice was significantly antagonized by pretreatment with quinpirole, a dopamine D 2/D 3 receptor agonist. Methamphetamine-induced place preference was also antagonized by pretreatment with 7-hydroxy- N,N-di- n-propyl-2-aminotetralin (7-OH-DPAT), a selective dopamine D 3 receptor agonist. On the other hand, 7-OH-DPAT produced significant place aversion in non-diabetic mice. 7-OH-DPAT produced neither place preference nor place aversion in diabetic mice. These results suggest that methamphetamine-induced place preference may be modulated by dopamine D 3 receptors. Furthermore, increased dopamine neurotransmission associated with the down-regulation of presynaptic dopamine D 3 receptor-mediated functions may account for the enhancement of methamphetamine's reinforcing effect in diabetic mice.

Role of spleen or spleen products in the reduced locomotor-enhancing effect of morphine in diabetic mice

In the present study, we examined the possibility that factor(s) derived from spleen cells are involved in the reduced morphine-induced hyperlocomotion in diabetic mice. The mean total locomotor activity after s.c. administration of morphine (20 mg/kg) in non-diabetic mice was significantly greater than that in diabetic mice. Splenectomized diabetic mice had a significantly higher sensitivity to morphine-induced hyperlocomotion than untreated or sham-operated diabetic mice. However, morphine-induced hyperlocomotion in non-diabetic mice was unaffected by splenectomy or sham-operation. Furthermore, 7 days after adoptive transfer of the supernatant of spleen cell homogenate (SSCH) from diabetic mice (SSCH-D), naive mice that had been injected with SSCH-D showed lower morphine-induced locomotor activity than mice which had been injected with SSCH from non-diabetic mice (SSCH-ND). These results suggest that some factor(s) derived from spleen cells may play an important direct or indirect role in the selective reduction of morphine's locomotor-enhancing effect in diabetic mice.

Antinociceptive effects of the selective non-peptidic δ-opioid receptor agonist TAN-67 in diabetic mice

The antinociceptive potencies of 2-methyl-4 aα-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12 aα-octahydro-quinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptidic δ-opioid receptor agonist, were examined using the acetic acid abdominal constriction test and the tail-flick test in diabetic mice. TAN-67, at doses of 3–100 mg/kg, i.p., produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal constrictions in both non-diabetic and diabetic mice. The antinociceptive effect of TAN-67 in the acetic acid abdominal constriction test in diabetic mice was greater than that in non-diabetic mice. Indeed, the ED 50 (95% confidence limits) value of TAN-67 for the inhibition of acetic acid-induced abdominal constrictions in diabetic mice (6.0 (3.5–10.5) mg/kg) was significantly lower than that in non-diabetic mice (31.4 (14.2–69.4) mg/kg). The antinociceptive effect of TAN-67 was not antagonized by pretreatment with either β-funaltrexamine, a selective μ-opioid receptor antagonist, or nor-binaltorphimine, a selective κ-opioid receptor antagonist. When 7-benzylidenenaltrexone (0.3 mg/kg, s.c.), a selective δ 1-opioid receptor antagonist, was administered 10 min before treatment with TAN-67, the antinociceptive effect of TAN-67 was significantly antagonized. However, naltriben, a selective δ 2-opioid receptor antagonist, had no significant effect on the antinociceptive effect of TAN-67. Furthermore, in the tail-flick test, TAN-67 at doses of 3–30 mg/kg, i.p., also produced a marked and dose-dependent antinociceptive effect in diabetic mice, but not in non-diabetic mice. In conclusion, TAN-67 produced an antinociceptive effect through the activation of δ 1-opioid receptors. Furthermore, the results of this study support our hypothesis that mice with diabetes are selectively hyperresponsive to δ 1-opioid receptor-mediated antinociception.

Antinociceptive effect of l-arginine in diabetic mice

The antinociceptive effect of L-arginine in streptozotocin-indueced diabetic mice was examined. Although s.c. administration of l-arginine produced a dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of l-arginine in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective δ-opioid receptor antagonist. However, neither β-funaltrexamine, a selective μ-opioid receptor antagonist, nor nor-binaltorphimin, a selective κ-opioid receptor antagonist, significantly affected the antinociceptive effect of l-arginine in diabetic and non-diabetic mice. These results suggest that l-arginine produces a marked antinociceptive effect in diabetic mice through the activation of δ-opioid receptors.

O-392 - Antinociceptive effect of L-arginine in diabetic mice.

Abstract The antinociceptive effect of L -arginine in streptozotocin-indueced diabetic mice was examined. Although s.c. administration of l -arginine produced a dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of l -arginine in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective δ-opioid receptor antagonist. However, neither β-funaltrexamine, a selective μ-opioid receptor antagonist, nor nor-binaltorphimin, a selective κ-opioid receptor antagonist, significantly affected the antinociceptive effect of l -arginine in diabetic and non-diabetic mice. These results suggest that l -arginine produces a marked antinociceptive effect in diabetic mice through the activation of δ-opioid receptors.

Antinociceptive effect of lipopolysaccharide from Pantoea agglomerans on streptozotocin-induced diabetic mice

The antinociceptive effect of lipopolysaccharide from Pantoea agglomerans (LPSp) in streptozotocin-induced diabetic mice was examined. Although subcutaneous (s.c.) administration of LPSp produced a dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of LPSp in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective δ-opioid receptor antagonist or nor-binaltorphimine, a selective κ-opioid receptor antagonist, but not by β-funaltrexamine, a selective μ-opioid receptor antagonist. These results suggest that LPSp produces a marked antinociceptive effect in diabetic mice through the activation of δ- and κ-opioid receptors.

Therapeutic efficacy of beta-lactam and aminoglycoside antibiotics on experimental pneumonia caused by Klebsiella pneumoniae B-54 in diabetic mice.

The therapeutic efficacy of six beta-lactam and aminoglycoside antibiotics were compared in diabetic mice with experimentally induced Klebsiella pneumoniae pneumonia. beta-Lactams caused a reduction in the numbers of bacteria, with clearance of bacteria from the lungs of diabetic and normal mice. The effect in diabetic mice, however, was very poor. In contrast thereto, no remarkable difference was seen between diabetic and normal mice when treated with aminoglycosides. The concentration of the test antibiotics to the lungs in diabetic mice was lower than in normal mice. The aminoglycosides were more effective than the beta-lactams. These data suggest that in treating acute and more chronic forms of pulmonary infection caused by K. pneumoniae in diabetic mice aminoglycoside antibiotics are particularly valuable, whereas beta-lactams must be given in large quantities using multiple administrations.