naloxone and Diabetes-Mellitus--Type-2

In this large population-based cohort, individuals with more-severe obesity, central obesity, or genetic predisposition for obesity are at higher risk of developing severe-COVID-19.. The use of different references for the classification of a high %BF implied a difference in the diagnostic sensitivity of the BMI. Higher cutoff points resulted in greater sensitivity and ability to differentiate individuals with and without obesity.

Topics: Acyclic Monoterpenes; Adipose Tissue; Adolescent; Adult; Aged; Aged, 80 and over; Air Pollutants; Air Pollutants, Occupational; Amino Acid Transport Systems; Analgesics, Opioid; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Arthrobacter; Bacteria; Bacteriological Techniques; Benzaldehydes; Biodegradation, Environmental; Biofilms; Biological Transport; Biomarkers; Biomass; Bioreactors; Body Composition; Body Mass Index; Brassica; Brazil; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Caco-2 Cells; Cadmium; Calcium; Calcium Carbonate; Calcium Channels; Catalysis; Cell Degranulation; Cell Line; Cell Membrane; Chitosan; Chromatography, High Pressure Liquid; Chromium; Cobalt; Cohort Studies; Colony Count, Microbial; Composting; Copper; COVID-19; Cross-Sectional Studies; Cytoplasm; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diarrhea; Diethylhexyl Phthalate; Dose-Response Relationship, Drug; Drug Implants; Drug Stability; Drug Synergism; Electroplating; Endometrial Neoplasms; Endometrium; Environmental Monitoring; Environmental Restoration and Remediation; Estradiol; Estrogens; Feces; Female; Food Microbiology; Food Preservation; Fruit and Vegetable Juices; Gasotransmitters; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gene Expression Regulation, Developmental; Genetic Predisposition to Disease; Glutathione; Gold; Graphite; Growth Hormone; Harm Reduction; Hot Temperature; Humans; Hydrocortisone; Hydrogen; Hydrogen Peroxide; Hydrogen Sulfide; Hydrogen-Ion Concentration; Ileum; Imidazoles; Injections, Intraperitoneal; Insecticides; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 5; Insulin-Like Growth Factor I; Intestinal Absorption; Light; Lignin; Liver; Magnetics; Male; Manganese; Mast Cells; Melanoma; Membrane Potentials; Metals; Methadone; Microbial Viability; Microplastics; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Middle Aged; Mitochondrial Swelling; Molecular Dynamics Simulation; Monophenol Monooxygenase; Morocco; Naloxone; Naltrexone; Nanocomposites; Nanomedicine; Nanoparticles; Narcotic Antagonists; Neonicotinoids; Nitric Oxide; Nitro Compounds; Nitrogen; Nitrogen Compounds; Obesity; Obesity, Abdominal; Occupational Exposure; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Oryza; Overweight; Oxidative Stress; Oxides; Oxygen; Perception; Photoelectron Spectroscopy; Plants; Plastics; Point Mutation; Polychlorinated Biphenyls; Polycyclic Aromatic Hydrocarbons; Potassium; Premenopause; Prodrugs; Prospective Studies; Protons; Pyrolysis; Qualitative Research; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Resins, Synthetic; Rhodamines; Risk Factors; ROC Curve; Salmo salar; SARS-CoV-2; Seawater; Severity of Illness Index; Sewage; Social Media; Soil; Soil Microbiology; Soil Pollutants; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Staining and Labeling; Stainless Steel; Steel; Stress, Physiological; Substance Abuse Treatment Centers; Symporters; T-Lymphocytes; Toluene; Triclosan; Ultraviolet Rays; Waist Circumference; Waste Disposal, Fluid; Wastewater; Water Purification; Welding; X-Ray Diffraction; Young Adult

Administration of synthetic human corticotropin-releasing factor (hCRF, 2 micrograms/kg body weight) during simultaneous application of the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) produced a significant increase in plasma C-peptide levels of six male Type 2 diabetic patients which even exceeded the postprandial values. This stimulatory effect of hCRF/naloxone on plasma C-peptide was less pronounced in six healthy men. hCRF alone did not provoke any reaction of plasma C-peptide in either group. The possibility of a paracrine, CRF-dependent mechanism in pancreatic islets which somehow involves inhibitory opioid receptors is preferentially discussed. Such a mechanism may underlie the stimulatory action of hCRF/naloxone on B cells and would explain the absent reaction of peripheral venous plasma C-peptide to hCRF alone as well as the amplifying effect of simultaneous opioid receptor blockade.

Topics: Blood Glucose; C-Peptide; Corticotropin-Releasing Hormone; Diabetes Mellitus, Type 2; Eating; Humans; Naloxone; Receptors, Opioid

Topics: Aged; Antitussive Agents; Blood Glucose; Codeine; Consciousness Disorders; Diabetes Mellitus, Type 2; Diagnosis, Differential; Drug Overdose; Female; Humans; Naloxone; Narcotic Antagonists

Pediatric pain management underwent many changes since the undertreatment of pain in children was reported in the literature in 1980. Increasing data also suggest that long-term behavioural effects can be observed in children, following pain episodes as early as in the neonatal period. Therefore, the knowledge about safe and effective management of pain in children should be applied with greater effectiveness into clinical practice. Other advances in the field include the findings of long-term residual behavioural and metabolic effects induced by pain experienced during the critical periods of development in laboratory animals. Recent data in laboratory animals and clinical data in children suggest that early repeated and/or severe pain and other stressful procedures applied in the perinatal periods may produce not only behavioral, but also important hormonal, immune and metabolic long-term effects. In this paper we shall report data on some metabolic conditions described in adult humans following disruption of hormonal-metabolic programming produced in the peri-natal period. Quite similar signs can be found between animal models and human conditions, most of them being connected with hypothalamus-pituitary-adrenal hormones (HPA) dysfunction. In addition, some signs in animal models, such as overweight and abdominal overweight are prevented by treatment with the μ- and δ-opioid receptor antagonist naloxone during the lactating period. This indicates that some long-term consequences following stress received during the early phases of life in mammals may be bound to the HPA system dysregulation, whereas others are bound to different (e,g., opioid) endogenous brain receptors and/or neuromediators alteration.

Topics: Adult; Animals; Animals, Newborn; Child; Diabetes Mellitus, Type 2; Female; Hormones; Humans; Hypothalamo-Hypophyseal System; Infant, Newborn; Male; Mice; Models, Biological; Naloxone; Oligonucleotides, Antisense; Pain; Pituitary-Adrenal System; Pregnancy; Pro-Opiomelanocortin; Stress Disorders, Post-Traumatic; Stress, Physiological; Stress, Psychological; Translational Research, Biomedical

In previous investigations we added a physical stress (mild pain) to the "classical" post-natal psychological stress in male mice, and we found that this combination produced a series of dysmetabolic signs very similar to mild human type-2 diabetes. Here, for the first time we demonstrate that within this diabetes model at least two groups of signs depend on the unbalance of two different endogenous systems. Newborn male mice were daily exposed to stressful procedures for 21 days (brief mother separation plus sham injection). Other groups underwent the same procedure, and also received naloxone (Na) to block μ-δ endogenous receptors, or a phosphorothioate antisense oligonucleotide (AS) directed against pro-opiomelanocortin (POMC)-mRNA [to block adrenocorticotropin (ACTH)- and POMC-derived opioid peptides]. Adult mice which received only post-natal stress increased body weight (+7.5%), abdominal overweight (+74%), fasting glycemia (+43%), plasma corticosterone (+110%), plasma (+169%) and pituitary (+153%) ACTH levels. Conversely, hypothalamic ACTH and corticotropin-releasing hormone (CRH) were reduced (-70% and -75%, respectively). Neonatal AS administration reverted all parameters to control values. Neonatal naloxone had little or no influence on glucose, corticosterone, ACTH, CRH levels, whereas it prevented body overweight and abdominal overweight. We conclude that, within this type-2 diabetes model in male mice at least two endocrino-neurohumoral systems are damaged, one concerning the opioid system, and the other concerning HPA hormones. The use of the two drugs was of primary importance to demonstrate this statement, and to demonstrate that these two groups of signs could be defined as "separate entities" following our complex post-natal stress model.

Topics: Adrenocorticotropic Hormone; Animals; Animals, Newborn; Corticosterone; Corticotropin-Releasing Hormone; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Hypothalamo-Hypophyseal System; Male; Maternal Deprivation; Mice; Naloxone; Phosphorothioate Oligonucleotides; Pituitary-Adrenal System; Pro-Opiomelanocortin; Receptors, Opioid; Stress, Psychological

Acupuncture at the Zhongwan acupoint has been widely used in traditional Chinese medicine to relieve symptoms of diabetes mellitus. Our study investigated the effect on plasma glucose of electroacupuncture applied at the Zhongwan acupoint in rat diabetic models. Plasma concentrations of insulin, glucagon and beta-endorphin- were also determined using radioimmunoassay. A decrease in plasma glucose was observed in rats after electroacupuncture (15 Hz, 10 mA) for 30 min at the Zhongwan acupoint. This was observed in normal rats and rat models with Type II (non-insulin-dependent) diabetes mellitus. No significant effect on plasma glucose was observed in rat models with Type I (insulin-dependent) diabetes mellitus: neither the streptozotocin (STZ)-induced diabetic rats nor the genetic (BB/W) rats. Further, the hypoglycaemic action of electroacupuncture stimulation disappeared in rats with insulin-resistance induced by an injection of human long-acting insulin repeated daily to cause the loss of tolbutamide-induced hypoglycaemia. An insulin-related action can thus be hypothesised. This hypothesis is supported by an increase in plasma insulin-like immunoreactivity after electroacupuncture stimulation in normal rats. Participation of glucagon was ruled out because there was no change in plasma glucagon-like immunoreactivity resulting from electroacupuncture stimulation. In addition to an increase in plasma beta-endorphin-like immunoreactivity, the plasma glucose lowering action of electroacupuncture stimulation at Zhongwan acupoint was abolished by naloxone in a sufficient dose to block opioid receptors. Thus we suggest that electroacupuncture stimulation at the Zhongwan acupoint induces secretion of endogenous beta-endorphin which reduces plasma glucose concentration in an insulin-dependent manner.

Topics: Acupuncture Points; Animals; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Electroacupuncture; Glucagon; Hypoglycemia; Insulin; Insulin Resistance; Male; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Tolbutamide

In order to investigate the relationships between glucose metabolism, insulin secretion and endogenous opioids in obese patients, we have studied the effects of a naloxone infusion on insulin and C-peptide release after a normal meal (800 kcal) eaten at 12.00 hr in 16 obese women, aged 20-61 yr, with a BMI ranging from 25 to 37.2 kg/m2, with normal glucose tolerance (Group 1) and with NIDDM (Group 2). Naloxone was administered in a bolus of 1.6 mg i.v., followed by a continuous infusion of 4 mg in 2 hr starting immediately after feeding. In Group 1 naloxone infusion significantly increased the glucose levels, but insulin secretion was unaffected. In Group 2, naloxone infusion failed to modify significantly the postprandial levels of glucose, insulin and C-peptide. Therefore, in our study naloxone infusion seems to have beta-endorphin-like effects in non-diabetic obese subjects by increasing their glycemic levels, with no evidence of expected insulin decrease. In diabetic obese patients we observed a trend towards decrease in glycemic values during naloxone infusion, as expected, due to insulin plasma levels increase. By these data we can hypothesise a complex regulatory role of opioids in metabolic balance in obesity. In diabetic patients, naloxone can improve the surviving insulin secretion with better glucose tolerance. In non-diabetic subjects naloxone exerts its effects, probably, on peripheral organs.

Topics: Adult; Analysis of Variance; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Infusions, Intravenous; Insulin; Middle Aged; Naloxone; Obesity

We report the case of a 61-year-old diabetic woman with end-stage renal disease who was on hemodialysis and who developed an encephalopathy and episodes of hypotension and hypoventilation, all of which showed rapid and dramatic responses on multiple occasions to the administration of the opiate antagonist naloxone. Improvement in encephalopathy was confirmed by electroencephalography. The patient had received no exogenous opiates and had a normal beta-endorphin level. She subsequently developed myoclonus and was treated for possible aluminum overload that was of borderline magnitude. We conclude that this patient had an encephalopathy that responded to opiate receptor blockade. Because of cerebrovascular disease, episodes of diminished blood pressure due to a state of increased opiate receptor stimulation may have unmasked this underlying encephalopathy. These effects may have been secondary to increased opiate-binding sites or to elevated central nervous system levels of endogenous opiates.

Topics: Brain Diseases; Diabetes Mellitus, Type 2; Electroencephalography; Female; Humans; Kidney Failure, Chronic; Middle Aged; Naloxone; Renal Dialysis

Administration of synthetic human corticotropin-releasing factor (hCRF, 2 micrograms/kg body weight) to 6 normal men produced a significant rise in plasma pancreatic polypeptide (PP) levels. This PP-stimulating effect of hCRF could not be observed in 6 male Type 2 diabetic patients. Simultaneous application of the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) led to a restoration of the normal PP response to hCRF in the diabetic patients, while in normal subjects, during this combined treatment, the hCRF-induced PP peak occurred somewhat delayed. Our results provide further evidence for a role of hCRF as a stimulatory factor of PP release in normal men. Moreover, it is suggested that endogenous opioids may be part of a modulatory principle co-regulating the secretion of PP. An elevated tone of such an opioidergic PP control system could be responsible for the impaired PP response to hCRF in Type 2 diabetics.

Topics: Adult; Corticotropin-Releasing Hormone; Diabetes Mellitus, Type 2; Humans; Kinetics; Male; Middle Aged; Naloxone; Pancreatic Polypeptide; Reference Values

Non insulin-dependent diabetes mellitus (Type II) is characterized by the loss of the acute insulin response to glucose. Met-enkephalin, catecholamines and prostaglandin E (PGE) have all been reported to inhibit the acute insulin response to glucose in normal humans. To evaluate the hypothesis that an increased sensitivity to these endogenous substances may play a role in defective insulin secretion in diabetes, we evaluated the effects of three blocking drugs upon the impaired insulin response to glucose in Type II diabetic subjects, as well as glucose-induced insulin secretion in normal humans. In diabetics, acute insulin responses to glucose were significantly increased by all the agents tested (naloxone, phentolamine and lysine acetylsalicylate), but only the cyclooxygenase inhibitor significantly augmented second phase insulin secretion and glucose disappearance rates. The combined infusion of the three agents caused a striking increase of the acute insulin response to glucose (response before: 3 +/- 2 uU/ml; after: 22 +/- 6 uU/ml, p less than 0.01). This was accompanied by a ninefold augmentation of the second phase of insulin secretion which was the result of a synergistic interaction between the three drugs (response significantly higher than the sum of single effects). In normals, insulin responses to glucose were also significantly increased by the combined infusions of the drugs, but to a significantly lesser extent than that of diabetics. This different degree of insulin potentiation between normals and diabetics under the infusion of the three agents persisted even when the prestimulus glucose level of normals was matched to that of diabetics by a glucose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Analgesics; Aspirin; Blood Glucose; Diabetes Mellitus, Type 2; Drug Interactions; Glucose; Humans; Insulin; Insulin Secretion; Kinetics; Lysine; Middle Aged; Naloxone; Phentolamine

The response of plasma immunoreactive met-enkephalin (IR-met-enkephalin) to ethanol (8 g by mouth) after chlorpropamide (250 mg daily for 14 d) was studied in three groups of non-insulin dependent diabetics (a) six diabetics who showed chlorpropamide alcohol flush (CPAF) and in whom the reaction could be blocked by indomethacin, (b) five diabetics who showed CPAF but in whom the flush could not be blocked by indomethacin and (c) five diabetics who did not show CPAF. A rise in plasma IR-met-enkephalin was observed in all three groups. When the two groups of flushers were re-tested with the addition of an infusion of naloxone a rise in plasma IR-met-enkephalin was still demonstrated in both groups regardless of whether the flush was blocked by naloxone. Naloxone blocked the flush only in those six subjects whose flush could be blocked by indomethacin. In five subjects, all flushers, CPAF was tested using intravenous and oral ethanol in doses producing similar plasma ethanol levels. A facial flush was induced by both intravenous and oral ethanol. In three flushers, plasma IR-met-enkephalin levels were measured during CPAF testing with both intravenous and oral ethanol. None showed a rise in plasma IR-met-enkephalin after intravenous ethanol, despite the appearance of a facial flush, whereas all showed a rise after oral ethanol. We therefore conclude that CPAF is unlikely to be caused by a rise in plasma IR-met-enkephalin.

Topics: Administration, Oral; Adult; Aged; Chlorpropamide; Diabetes Mellitus, Type 2; Drug Interactions; Enkephalin, Methionine; Ethanol; Female; Flushing; Humans; Indomethacin; Injections, Intravenous; Male; Middle Aged; Naloxone