Effect of metformin on liver insulin metabolism and regional blood flow.
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Animals↗
Biomedical subjects
M Chianelli
Publications and source records attributed to M Chianelli.
Retroviruses and diabetes in animal models: hypotheses for the induction of the disease.
This review examines the association between retroviruses and diabetes in the mouse model, the role of retroviruses in the pathogenesis of Type 1 diabetes and the mechanisms by which retroviruses can induce an autoimmune reaction. Three putative mechanisms are considered: the expression of retroviral protein(s) on the beta-cell surface as the first step in immune response against beta cells; the homology of a retroviral product with a self antigen inducing a cross-reacting autoimmune response (molecular mimicry); and a retroviral product showing homology with interleukin-2 and inducing T-cell activation against beta-cell antigens and loss of tolerance. These findings are discussed for their possible implications in the pathogenesis of human Type 1 diabetes.
Animals↗
Beta-endorphin in silent duodenal ulcer.
OBJECTIVE: To investigate whether duodenal ulcer patients with painful active peptic ulcer and those with silent active ulceration have different plasma beta-endorphin levels. PATIENTS: Forty-five patients (28 men and 17 women), aged 38-50 years, with at least a 5-year history of duodenal ulceration. Twenty-two patients had painful symptoms, while 23 had silent active duodenal ulcer. METHODS: Beta-endorphin plasma levels (pmol/l) were measured during an acute episode of duodenal ulcer, before and after antisecretory therapy with omeprazole. In three patients we measured the concentration of beta-endorphin in gastric juice before and after pentagastric (6 micrograms/kg subcutaneous) stimulation. RESULTS: The basal values of beta-endorphin in both patients with asymptomatic and those with symptomatic duodenal ulcer showed no difference before or after 30 days of antisecretory treatment. Plasma beta-endorphin levels (median values in the normal range < 12 pmol/l) were significantly higher (Student's t-test, P < 0.005) in the asymptomatic than in symptomatic patients, both before (9.07 +/- 4.8 versus 5.6 +/- 2.5 pmol/l) and after (8.7 +/- 4.1 versus 5.7 +/- 2.4 pmol/l) omeprazole treatment. The highest levels of beta-endorphin were found in four patients with a negative history for any pain symptom (visual analogue scale score 0). CONCLUSIONS: Our data suggest that the opioid system, particularly beta-endorphin, is involved in the perception of pain in duodenal ulcer disease, which explains the silent clinical characteristics of some peptic ulcers. In addition, the concentration of beta-endorphin found in gastric juice indicates a possible peripheral effect of this opiate.
Adult↗
SPECT imaging with 111In-octreotide for the localization of pancreatic insulinoma.
We evaluated the sensitivity of 111In-Octreotide scintigraphy in the diagnosis of pancreatic insulinoma in a selected number of patients. In addition, we compared the results of scintigraphy with those of other conventional diagnostic techniques. Seven patients with surgically confirmed insulinoma (< 1.5 cm in diameter) of the pancreas were studied. Before surgery, patients underwent arteriography with Ca-gluconate, CT scan, and 111In-Octreotide scintigraphy. 111In-Octreotide scintigraphy showed a higher diagnostic specificity (85%) than selective arteriography (83%) or CT scan (57%). We conclude that 111In-Octreotide scintigraphy should always be performed before surgery in cases of pancreatic insulinoma and that a SPECT acquisition should be performed both 6 and 24 hours post-injection in order to increase the diagnostic sensitivity of the test.
Adolescent↗
New approach for in vivo detection of insulitis in type I diabetes: activated lymphocyte targeting with 123I-labelled interleukin 2.
Insulitis is considered the histopathological hallmark of type I (insulin-dependent) diabetes. In the non-obese diabetic (NOD) mouse, diabetes has never been observed in the absence of insulitis. The in vivo detection of insulitis could be of relevance for early prediction of diabetes. As approximately 15% of islet-infiltrating lymphocytes express interleukin 2 receptors, we have labelled recombinant interleukin 2 with 123I and used this radiopharmaceutical to detect insulitis by gamma camera imaging. We studied 71 prediabetic NOD and 27 normal Balb/c mice. Labelled alpha-lactalbumin was used as the control protein. In the first set of experiments we studied the tissue distribution of radiolabelled interleukin 2 in isolated organs from animals sacrificed at different time points. Higher radioactivity was detected in the pancreas of NOD mice injected with labelled interleukin 2, as compared to NOD mice receiving labelled alpha-lactalbumin (p < 0.003 at 20 min: p < 0.001 at 40 min; p < 0.001 at 60 min) or Balb/c mice injected with labelled interleukin 2 (p < 0.05 at 40 min; p < 0.001 at 60 min). In another set of experiments, gamma camera images have been acquired after injection of 123I-labelled interleukin 2. Radioactivity in the pancreatic region of prediabetic NOD and Balb/c mice showed similar kinetics to those observed by single organ counting, with higher accumulation in the pancreatic region of NOD mice (p < 0.04 after 22-45 min in NOD mice vs Balb/c mice).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A simple method for the evaluation of receptor binding capacity of modified cytokines.
We have developed a flow cytometric method to evaluate the binding of interleukin-2 analogues to receptors. The method relies on competition for binding between a fluorescein-conjugated monoclonal antibody (MoAb) directed against the human interleukin-2 receptor alpha chain (fluorescein isothiocyanate (FITC) anti-IL-2R) and the test protein. IL-2R positive cells are incubated with FITC-anti-IL-2R MoAb in the presence of native IL-2 or IL-2 iodinated by either the chloramine-T or the lactoperoxidase-glucose-oxidase method. The binding of IL-2 is indicated by decreased fluorescence. This method is suitable for measuring the binding capacity of modified IL-2 molecules and avoids the need for radioactive tracers. It provides a simple and reproducible technique, which can be extended readily to the study of the receptor binding capacity of cytokines conjugated with toxins, drugs or other molecules.
Antibodies, Monoclonal↗
A radiopharmaceutical for imaging areas of lymphocytic infiltration: 123I-interleukin-2. Labelling procedure and animal studies.
The labelling of interleukin-2 (IL-2) with 123I and its in vivo application for imaging chronic pathological lymphocytic infiltrations are described. The lactoperoxidase/glucoseoxidase technique was the labelling method of choice leading to immunoreactive IL-2 with high specific activity. Labelled IL-2 was injected in diabetes-prone non-obese diabetic (NOD) mice with pancreatic lymphocytic infiltration. As control animals, Balb/c mice were used. As specificity control, monoclonal antibodies AMT13 and UCHT1, bovine serum albumin and alpha-lactalbumin were radioiodinated and injected in mice. Eighteen NOD mice and four control Balb/c mice were used for gamma camera imaging experiments. Fifty-four NOD and 20 Balb/c mice were used for time course single organ counting and autoradiography. Gamma camera images showed that radioactivity accumulated in the pancreatic region from the 10th minute onwards in NOD mice injected with 123I-IL-2 but not in Balb/c mice, or in NOD mice injected with control radiopharmaceuticals. These findings were confirmed by counting the radioactivity present in single organs. Autoradiography of NOD pancreas, after injection of labelled IL-2, showed that radioactivity was specifically associated with infiltrating lymphocytes. In conclusion, this technique is highly specific and easy to perform and we suggest its application in humans for in vivo detection of areas of lymphocytic infiltration.
Animals↗
Retinol binding protein: a short half life determinant of protein non enzymatic glycation in diabetes.
The non enzymatic glycation of circulating and structural proteins is the main biochemical consequence of the chronic hyperglycaemia of diabetes mellitus. Retinol binding protein (RPB) is a 21K plasma globulin with an half life of 12 hr; its non enzymatic glycation may reflect the variation of short term metabolic control (1-4 days). In this study two blood samples were withdrawn at four days interval from 24 non insulin dependent diabetic patients. Glycated RBP was measured by a two-site immunoradiometric assay and its variations correlated with the correspondent changes in the blood glucose level. A significant correlation (r = 0.471; p less than 0.02) was found between the time 4/time 0 ratios of glycated RBP and the time 4/time 0 ratios of blood glucose. These data suggest that measurement of non-enzymatically glycated RBP may be a useful tool to evaluate the short term state of non enzymatic glycation in diabetes.
Biomarkers↗
In vivo labelling of activated T lymphocytes by i.v. injection of 123I-IL2 for detection of insulitis in type 1 diabetes.
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Animals↗
Thymopentin administration and increase of sero-conversion after B-hepatitis vaccine in diabetic patients.
We have previously reported that 40% of diabetic patients have an impaired specific immune response after vaccination against B-hepatitis. Thymopentin (TP5), the active site of thymopoietin hormone, has been shown to increase antibody response (HbsAb) following B-hepatitis vaccination in several disease conditions. In the present study TP5 (50 mg) was administered subcutaneously three times per week to 17 diabetic patients for a week prior B-hepatitis vaccination and for three weeks afterwards. Sero-conversion was observed after the third dose of vaccine in 15 out of 17 (88%) patients and in 94% of a group of normal subjects acting as control. Although the median HbsAb titre was significantly lower in diabetics compared to normal subjects, we conclude that administration of TP5 in diabetic patients increases the rate of sero-conversion following B-hepatitis vaccination.
Adjuvants, Immunologic↗
Infliximab therapy in patients with secondary Sjögren's syndrome: functional evaluation.
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Adult↗
Effect of Tenidap, a novel anti-inflammatory compound on islet lymphocytic infiltration and diabetes incidence in the non obese diabetic (NOD) mouse.
Tenidap, a novel compound inhibiting cyclooxygenase and lipoxygenase, also possessing an inhibitory effect on interleukin-1 secretion by in vitro activated macrophages, has been administered to the non obese diabetic (NOD) mouse to evaluate its action on the induction and progression of insulitis and the diabetes incidence. Animals were allocated to three groups (group A: control group; group B: 12 mg/kg/day Tenidap; group C: 36 mg/kg/day Tenidap); female animals only were followed up to investigate the effect on diabetes incidence. The administration of Tenidap influenced the natural course of insulitis in male NOD mice; thus, at 60 and 100 days of age the mean percentage of infiltrated islets was significantly reduced compared to control animals (p less than 0.02). Moreover the severity of lymphocytic infiltration at 60 days of age was reduced in male mice of group B and C compared to control mice (p less than 0.004 and p less than 0.0001, respectively) whereas at 100 days of age this difference was not significant. However the progression towards severe insulitis in male animals receiving Tenidap was halted compared to control animals. Tenidap had also a significant dose dependent effect at 60 days on the severity of lymphocytic infiltration (group B vs. group C, p less than 0.01). By contrast, this agent had no effect on the degree of insulitis and diabetes incidence in female NOD mice. In both sexes at the end of follow-up a significant reduction in body weight was observed in animals of Group C compared to control animals (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
In vivo measurement of immunoglobulin accumulation in the pancreas of recent onset type 1 diabetic patients.
OBJECTIVE: The possibility to quantify in vivo the severity of the inflammatory process in the pancreas of patients with recent onset insulin dependent diabetes mellitus (IDDM) could be of great relevance for follow-up studies involving immunotherapy. Scintigraphy with radiolabelled human polyclonal immunoglobulins (99mTc-HIG) is currently used for the diagnosis and follow-up of several acute and chronic inflammatory diseases. In this longitudinal study we have investigated to what extent 99mTc-HIG accumulate in the pancreas of patients with recent onset IDDM and in subjects at risk to develop IDDM. METHODS: Combined computerised tomography and gamma camera imaging were used to measure the radioactivity in the pancreatic region, as the pancreas/bone radioactivity ratio (P/B). Patients with IDDM (n = 15) were investigated at the time of diagnosis and after 1 year. Five pre-diabetic ICA+ve subjects and 8 age and sex matched normal subjects were also investigated. RESULTS: Eight out of 15 newly diagnosed IDDM patients and 2/5 ICA+ve subjects showed a significant accumulation of radiolabelled HIG in the pancreas (P/B higher than the upper 1st centile of normal subjects). One year after the diagnosis a significant accumulation of immunoglobulins was still detectable in the pancreas of IDDM patients positive who were positive at diagnosis. CONCLUSIONS: These results suggest that immunoglobulins home and bind to the pancreas of patients with recent onset IDDM and also in some ICA+ve individuals. This may reflect an increased vascular permeability of pancreatic capillaries as a consequence of the inflammatory process involving the islets. Thus, this technique may be useful for monitoring the efficacy of immune intervention at diagnosis.
Adolescent↗