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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine of the innate immune system that plays a major role in the induction of immunoinflammatory responses. To examine the role of endogenous MIF in the pathogenesis of type 1 diabetes (TID) we evaluated the effects of administration of neutralizing anti-MIF antibodies to NOD mice with accelerated forms of diabetes induced by injection of cyclophosphamide or by transfer of diabetogenic spleen cells. Both accelerated forms of diabetes were markedly reduced by anti-MIF antibody. Furthermore, MIF-deficient (MIF(-/-)) mice were less susceptible to the induction of immunoinflammatory diabetes, insulitis and apoptosis within the endocrine pancreas by multiple low doses of streptozotocin (MLD-STZ) than genetically matched wild type (WT) mice. MIF deficiency resulted in lower proliferation and lymphocyte adhesion, as well as reduced production from the spleens and peritoneal cells of a variety of inflammatory mediators typically associated with development of the disease including IL-12, IL-23, TNF-alpha, and IL-1beta. Furthermore, MIF deletion affected the production of IL-18, TNF-alpha, IL-1beta, and iNOS in the islets of Langerhans. These data, along with the higher expression of IL-4 and TGF-beta observed in the periphery and in the pancreas of MLD-STZ-challenged MIF(-/-) mice as compared to WT controls suggest that MIF deficiency has induced an immune deviation towards protective type 2/3 response. These results suggest that MIF participates in T1D by controlling the functional activity of monocytes/macrophages and T cells and modulating their secretory capacity of pro- and anti-inflammatory molecules.
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PMID:Macrophage migration inhibitory factor (MIF) is necessary for progression of autoimmune diabetes mellitus. 1806 33

We employed streptozotocin-induced diabetic rats (STZ-diabetic rats) as type 1 diabetes-like animal models to investigate the mechanism(s) of antihyperglycemic action produced by syringin, an active principle purified from the rhizome and root part S of ELEUTHEROCOCCUS SENTICOSUS (Araliaceae). Bolus intravenous (i. v.) injection of syringin dose-dependently decreased the plasma glucose of STZ-diabetic rats in 30 minutes in a way parallel to the increase of plasma beta-endorphin-like immunoreactivity (BER). Syringin enhanced BER release from the isolated adrenal medulla of STZ-diabetic rats in a concentration-dependent manner from 0.001 to 10 micromol/l. Bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of syringin (1 mg/kg, i. v.) including the plasma glucose-lowering effect and the plasma BER-elevating effect. Also, syringin failed to lower plasma glucose in the presence of micro-opioid receptor antagonists and/or in the micro-opioid receptor knockout diabetic mice. In conclusion, the obtained results suggest that syringin can enhance the secretion of beta-endorphin from adrenal medulla to stimulate peripheral micro-opioid receptors resulting in a decrease of plasma glucose in diabetic rats lacking insulin.
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PMID:Increase of beta-endorphin secretion by syringin, an active principle of Eleutherococcus senticosus, to produce antihyperglycemic action in type 1-like diabetic rats. 1807 69

Decreased hind limb pressure pain threshold (PPT) is an early indicator of insulinopenia and neuropathy developing in STZ-rat models of type 1 diabetes and pre-diabetes. To test if pain on pressure is also a hallmark of compensated insulin resistance and type 2 diabetes in this work we measured PPT of Zucker lean (ZL), Zucker fatty (ZF) and Zucker fatty diabetic rats (ZDF; 8 animals per group). Using clinically accepted cut-off values for diagnosis of human diabetes and pre-diabetes, at 6th week of age (the study entry), all animals maintained random blood glucose within a normal range (< 7.9 mM). Over the following 4 weeks, the random glucose remained normal in lean and ZF rats; it however crossed 11 mM cut-off for the diagnosis of diabetes in all ZDF rats. With no detectable relation to blood glucose levels or changes throughout the study, lean, ZF and ZDF rats maintained respectively highest, intermediate and lowest PPT levels (83+/-1, 70+/-1 and 59+/-1 g; mean values for all tests per group). Thus in Zucker rat model, type 2 diabetes-associated impairment of nerve function precedes the development of hyperglycemia. Furthermore, since normoglycemic, but displaying decreased PPT, ZF rats were strongly hyperinsulinemic (plasma insulin concentration 30+/-4 ng/ml vs. 2.4+/-0.3 ng/ml in lean rats) these data suggest that hyperinsulinemia compensating for glucose metabolism might not restore compromised nerve function.
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PMID:Pressure pain precedes development of type 2 disease in Zucker rat model of diabetes. 1879 4

Macroangiopathy is a major complication of diabetes mellitus in which dysfunction of vascular endothelium induced by excessive oxidative stress is an early and key determinant. As an endogenous antioxidant, taurine possesses endothelial protective effect in vitro. LOX-1 is an endothelial receptor for oxidized low-density lipoprotein (oxLDL) which might mediate endothelial dysfunction and subsequent atherogenesis in diabetes. We used streptozotocin-induced rats as models of type 1 diabetes to evaluate the protective effect of taurine against vascular endothelial dysfunction in type 1 diabetes and the possibly involved molecule mechanism. Eight male Wistar rats were used as normal control group. Sixteen diabetic rats induced by one single injection of streptozocin (60 mg/kg, i.p.) were randomly divided into two groups after the diabetes onset: diabetes mellitus group and taurine-treated diabetes group. 6 weeks afterward, endothelium-dependent vasodilation of isolated thoracic aorta, serum oxLDL and soluble intercellular adhesion molecule (sICAM-l) levels, LOX-1 and intercellular adhesion molecule (ICAM-1) expression on aortas were determined respectively. Streptozocin-induced diabetic rats were complicated with excessive oxidative stress and endothelial dysfunction: increased serum oxLDL and sICAM-1, inhibited endothelium-dependent vasodilator responses to acetylcholine (1 nM-0.1 microM). Simultaneously, LOX-1 and ICAM-1 expression were enhanced in aortas of diabetic rats; whereas blunted endothelium-dependent vasodilator responses to acetylcholine, increased serum oxLDL and sICAM-1 level as well as overexpression of LOX-1 and ICAM-1 were all attenuated significantly by taurine treatment. In conclusion, taurine improves vascular endothelial dysfunction induced by experimental type 1 diabetes and this effect might be associated with downregulation of LOX-1 and ICAM-1 expression on aortic vascular endothelium via its antioxidative property.
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PMID:Taurine rescues vascular endothelial dysfunction in streptozocin-induced diabetic rats: correlated with downregulation of LOX-1 and ICAM-1 expression on aortas. 1879 3

Diabetes is characterized by elevated fasting blood glucose (FBG) resulting from improper insulin regulation and/or insulin resistance. Herein we used female C57BL/6J mouse models for type 1 diabetes (streptozotocin [STZ] treatment) and type 2 diabetes (high-fat diet) to examine the ability of 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII) to intervene in the progression of diabetes. THII (100 microM in drinking water) significantly diminished and partially reversed the increase in FBG levels produced by STZ. After 10 weeks on a high-fat diet, mice had normal FBG levels, but exhibited fasting hyperinsulemia and loss of glucose tolerance. THII significantly diminished these changes in glucose and insulin. In isolated liver mitochondria, THII inhibited succinate-dependent H(2)O(2) production, while in white adipose tissue, THII inhibited NADPH oxidase-mediated H(2)O(2) production and lipid peroxidation. Without intervention, such oxidative processes might otherwise promote diabetogenesis via inflammatory pathways. THII also increased O(2) consumption and lowered respiratory quotient (CO(2) produced/O(2) consumed) in vivo, indicating a greater utilization of fat for metabolic fuel. Increased metabolic utilization of fat correlated with a decrease in the rate of body weight gain in THII-treated mice fed the high-fat diet. We conclude that THII may retard the progression of diabetes via multiple pathways, including the inhibition of oxidative and inflammatory pathways.
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PMID:Tetrahydroindenoindole inhibits the progression of diabetes in mice. 1882 64

Diabetes-induced complications are associated with mitochondrial dysfunction and increasing evidence suggests that diabetes has an adverse effect on male reproductive function. The STZ-induced diabetic rat was used as an animal model for the type 1 form of the disease with the aim of determining its effects in spermatogenesis and testicular mitochondrial function. Several aspects of mitochondrial function were measured, including respiratory and electric potential function, as well as mitochondrial calcium loading capacity. Additionally oxidative stress production, antioxidant levels and possible apoptotic alterations were also evaluated. We observed that diabetic animals present alterations in spermatogenesis in both the testis and epidydimus. However, and surprisingly, the overall results in mitochondrial parameters failed to reveal severe testicular mitochondrial dysfunction in diabetic animals, with the exception of a decrease in calcium load. Taken together, results suggest that in animal models that mimic untreated type 1 diabetes the severe effects of the condition on spermatogenesis are not directly mitochondrial-mediated.
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PMID:Testicular mitochondrial alterations in untreated streptozotocin-induced diabetic rats. 1910 Mar 45

Streptozotocin (STZ) given intravenously destroys pancreatic beta cells and is widely used in animal models to mimic type 1 diabetes. The effects of STZ on the clinical state of health and metabolism were studied in six high health certified domestic pigs weighing 19+/-1.3 kg at the start of the experiment. A single STZ dose of 150 mg/kg of body weight successfully induced hyperglycaemia and alterations in amino acid metabolism. Within 9 h after STZ administration, the blood glucose values fell from 5.4-7.5 mmol/L to 0.8-2.2 mmol/L. Hypoglycaemia was treated with 0.5 g glucose/kg body weight. In all pigs, hyperglycaemia was produced 24 h after STZ treatment, and 3 days after STZ injection, the glucose concentration was >25 mmol/L. Mean C-peptide concentration was 0.25+/-0.16 microg/L since 2 days after STZ injection until the end of the study. The serum concentration of the branched-chain amino acids (BCAA) increased four-fold, and alanine and taurine decreased by approximately 70% and 50%, respectively, after STZ treatment. All but one pig remained brisk and the physical examination was normal except for a retarded growth rate and a reduction of the skeletal muscle. At the end of the study, the pigs were moderately emaciated. Postmortem examination confirmed muscle wasting and a reduction of abdominal and subcutaneous fat. In conclusion, STZ-induced diabetes in pigs fulfils the requirements for a good animal model for type 1 diabetes with respect to clinical signs of the disease and alterations in the carbohydrate and amino acid metabolism.
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PMID:Effects of streptozotocin-induced diabetes in domestic pigs with focus on the amino acid metabolism. 1924 3

Recently, we characterized the more severe nature of hearing loss in aged Type 2 diabetic human subjects [Frisina, S.T., Mapes, F., Kim, S., Frisina, D.R., Frisina, R.D., 2006. Characterization of hearing loss in aged type II diabetics. Hear. Res. 211, 103-113]. The current study prospectively assessed hearing abilities in middle age CBA/CaJ mice with Type 1 diabetes mellitus (T1DM) (STZ injection) or Type 2 diabetes mellitus (T2DM) (high fat diet), for a period of 6 months. Blood glucose, body weight and auditory tests (Auditory Brainstem Response-ABR, Distortion Product Otoacoustic Emissions-DPOAE) were evaluated at baseline and every 2 months. Tone and broad-band noise-burst responses in the inferior colliculus were obtained at 6 months. Body weights of controls did not change over 6 months (approximately 32 g), but there was a significant (approximately 5 g) decline in the T1DM, while T2DM exhibited approximately 10 g weight gain. Blood glucose levels significantly increased: 3-fold for T1DM, 1.3-fold for T2DM; with no significant changes in controls. ABR threshold elevations were found for both types of diabetes, but were most pronounced in the T2DM, starting as early as 2 months after induction of diabetes. A decline of mean DPOAE amplitudes was observed in both diabetic groups at high frequencies, and for the T2DM at low frequencies. In contrast to ABR thresholds, tone and noise thresholds in the inferior colliculus were lower for both diabetic groups. Induction of diabetes in middle-aged CBA/CaJ mice promotes amplification of age-related peripheral hearing loss which makes it a suitable model for studying the interaction of age-related hearing loss and diabetes. On the other hand, initial results of effects from very high blood glucose level (T1DM) on the auditory midbrain showed disruption of central inhibition, increased response synchrony or enhanced excitation in the inferior colliculus.
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PMID:Interactions of hearing loss and diabetes mellitus in the middle age CBA/CaJ mouse model of presbycusis. 1927 13

Insulin dependent diabetes mellitus (IDDM) results from irreversible loss of beta cells (beta-cells) of the pancreas. A Streptozotocin (STZ)-induced diabetes in animal model mimics, in some aspects, recent onset IDDM. This study was conducted to investigate the effect of nicotinamide on experimentally-induced IDDM. Thirty Spraque Dawley rats were divided into 3 groups; a control group, a diabetic group which received an intraperitoneal (i.p.) injection of 55 mg/kg STZ and a nicotinamide group (1g/kg/day) which were dosed orally for 3 days followed by (i.p.) STZ (55 mg/kg) with the nicotinamide treatment continuing for an additional 14 days. Rats receiving STZ became diabetic after 2 weeks. This diabetic group showed hyperglycemia, and a very low level of C-peptide. Furthermore, pancreatic islets exhibited increased nitric oxide (NO) production together with an increased apoptotic index (as detected by TUNEL and electron microscopy). Nicotinamide treatment prevented STZ-induced diabetes, it also antagonized an increase in NO, and inhibited beta-cell apoptosis. Fasting blood glucose, serum insulin and serum C-peptide were all within the normal range in the nicotinamide group. The nicotinamide protection of beta-cells may be facilitated via inhibition of apoptosis and nitric oxide generation. It is suggested that nicotinamide might be considered an effective agent for the prevention and treatment of IDDM in prediabetic, and early stages, of IDDM.
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PMID:Effect of nicotinamide on experimental induced diabetes. 1927 54

The anti-hyperglycemic and immunomodulatory activities of the ethanol extract from Paecilomyces Hepiali Chen (PHC), a Chinese medicine, were investigated in streptozotocin-induced type 1 diabetic (T1DM) mice. Male Balb/c mice, which were i.p. injected with streptozotocin (STZ, 50 mg/kg, for 5 consecutive days) on Day 7, were orally administered saline (the normal control and diabetic control group), Metformin (60 mg/kg, b.w., positive group), or the extract (100 mg/kg, b.w., PHC prevention group) from Day 1 to Day 28, Mice i.p. injected with streptozotocin (STZ, 50 mg/kg, b.w.) for 5 consecutive days prior to PHC treatment (100 mg/kg, b.w.) were used as the PHC treatment group. The effects of PHC on postprandial blood glucose concentrations, plasmatic insulin levels, morphology of pancreatic beta cells and CD4(+) T cells proliferation after 28-day treatment were monitored. Results showed that PHC administered 6 days before STZ induction of diabetes in mice significantly decreased blood glucose level (p < 0.01). An increase of insulin level was also observed as compared to those in the diabetic control group (p < 0.01). In addition, fewer inflammatory cells infiltrated the pancreatic islet and fewer beta cells death by apoptosis within the inflamed islets were observed. More importantly, the CD4(+) T cell proliferation was remarkably attenuated ex vivo in mice preventively treated with PHC (p < 0.01). In comparison to the PHC prevention group, no significant hypoglycemia, changes of insulin level and beta cell protection were observed in mice treated with PHC after STZ administration. Our findings demonstrated that preventive administration of PHC protected beta cells from apoptosis in type 1 diabetes induced by STZ, and the underlying mechanism may be involved in suppressing CD4(+) T cells reaction, reducing inflammatory cells infiltration and protecting beta cell apoptosis in pancreatic islet.
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PMID:beta cell protecting and immunomodulatory activities of Paecilomyces Hepiali Chen mycelium in STZ induced T1DM mice. 1950 78


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