beta-endorphin and Hyperglycemia

Plasma beta-endorphin (beta-E) concentration was determined before, during, and after a standardized incremental exercise test to maximal capacity in eight type I diabetic patients and eight normal control subjects. Diabetic patients were studied under normoglycemic and hyperglycemic conditions in a single-blind random fashion to differentiate between the effects of acute hyperglycemia and of diabetes per se on the beta-E response to exercise. The perceived magnitude of leg effort elicited by exercise was evaluated using a category scale. Whereas plasma beta-E concentrations increased in control subjects with increasing workload, causing significantly higher beta-E levels at the end of exercise than at the beginning (P < .001), no such increase could be observed in the diabetic patients under normoglycemic and hyperglycemic conditions. In addition, baseline plasma beta-E concentrations were significantly lower in normoglycemic (P < .01) and hyperglycemic (P < .001) diabetic patients than in control subjects. Even during the recovery period, patients' beta-E levels remained significantly lower than those of control subjects. At submaximal levels of power output, the perceived intensity of leg effort was significantly higher in normoglycemic and hyperglycemic diabetic patients than in control subjects. We conclude that in type I diabetic patients, the ability of the endogenous opioid system to respond to exercise-induced stress is impaired under hyperglycemic and even under normoglycemic conditions. Considering the effect of endogenous opioids on stress tolerance, such changes may compromise exercise performance in diabetic patients.

Topics: Adult; beta-Endorphin; Diabetes Mellitus, Type 1; Exercise Test; Female; Hemodynamics; Humans; Hyperglycemia; Lactates; Leg; Male; Physical Exertion; Respiratory Mechanics; Single-Blind Method

The levels of beta-endorphin, insulin, cortisol, GH, glucagon, prolactin and TSH were measured in serum samples of 9 hyperglycaemic patients (3 female, 6 male) with a mean age of 4.1 years admitted to the pediatric emergency unit. All patients were in acute stress due to severe diseases (acute gastroenteritis, bronchopneumonia, septicaemia, etc.). Initial and repeat blood samples for hormone determination were taken at admission and in the recovery phase (after 4-6 weeks of treatment). OGTT was also performed in the recovery phase. The hyperglycaemia, monitored hourly following the initial determination, returned to normal in all patients in 1-5 h without specific treatment. Mean serum glucose values at admission and in the recovery phase were 287.0 and 84.1 mg/dl. Concomitant to the hyperglycaemia encountered in these patients in the acute phase of stress, an increase was noted in all hormone levels excluding glucagon and cortisol. All elevated hormone levels fell to normal in 4-6 weeks with significant differences from initial levels for beta-endorphin (P < 0.05) and insulin (P < 0.01). OGTT gave a normal curve. These results indicate that stress hyperglycaemia, despite high insulin levels, is associated with an increase in beta-endorphin levels. The results also show that hyperglycaemia in acute disease does not alter OGTT in short-term follow up.

Topics: Acute Disease; beta-Endorphin; Blood Glucose; Bronchopneumonia; Child; Child, Preschool; Female; Gastroenteritis; Glucagon; Growth Hormone; Hormones; Humans; Hydrocortisone; Hyperglycemia; Infant; Insulin; Male; Prolactin; Sepsis; Stress, Physiological; Thyrotropin

Diosmin is one of the flavonoids contained in citrus and has been demonstrated to improve glucose metabolism in diabetic disorders. However, the mechanism(s) of diosmin in glucose regulation remain obscure. Therefore, we investigated the potential mechanism(s) for the antihyperglycaemic action of diosmin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Diosmin lowered hyperglycaemia in a dose-dependent manner in STZ-diabetic rats. This action was inhibited by naloxone at a dose sufficient to block opioid receptors. Additionally, we determined the changes in plasma β-endorphin-like immunoreactivity (BER) using enzyme-linked immunosorbent assay (ELISA). Diosmin also increased BER dose-dependently in the same manner. Repeated treatment of STZ-diabetic rats with diosmin for 1 week resulted in an increase in the expression of the glucose transporter subtype 4 (GLUT 4) in the soleus muscle and a reduction in the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. These effects were also inhibited by naloxone at a dose sufficient to block opioid receptors. Bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of diosmin, including both the reduction in hyperglycemia and the elevation of plasma BER. In conclusion, our results suggest that diosmin may act on the adrenal glands to enhance the secretion of β-endorphin, which can stimulate the opioid receptors to attenuate hepatic gluconeogenesis and increase glucose uptake in soleus muscle, resulting in reduced hyperglycemia in STZ-diabetic rats.

Topics: Animals; beta-Endorphin; Blood Glucose; Citrus; Diabetes Mellitus, Type 1; Diosmin; Dose-Response Relationship, Drug; Flavonoids; Hyperglycemia; Hypoglycemic Agents; Male; Rats; Rats, Sprague-Dawley

Canavanine is a guanidinium derivative that has the basic structure of a ligand for the imidazoline receptor (I-R). Furthermore, canavanine is found in an herb that has been shown to improve diabetic disorders. Thus, the present study was designed to investigate the anti-hyperglycemic action of canavanine in rats with streptozotocin (STZ)-induced type 1-like diabetes. Canavanine decreased hyperglycemia in the STZ-induced diabetic rats, and this action was blocked by the antagonist specific to imidazoline I-2 receptors (I-2R), BU224, in a dose-dependent manner. Additionally, canavanine increased the plasma β-endorphin level, as measured using enzyme-linked immunosorbent assay (ELISA), and this increase was also blocked by BU224 in the same manner. Moreover, amiloride at a dose sufficient to block I-2AR attenuated the actions of canavanine, including the increased β-endorphin level and the antihyperglycemic effect. Otherwise, canavanine increased the radioactive glucose uptake into skeletal muscles isolated from the diabetic rats. Furthermore, canavanine increased the phosphorylation of AMPK measured using Western blot analysis in these isolated skeletal muscles in a dose-dependent manner. Additionally, the insulin sensitivity of the diabetic rats was markedly increased by canavanine, and this action was also blocked by BU224. Overall, canavanine is capable of activating imidazoline I-2R; I-2AR is linked to an increase in the plasma level of β-endorphin, and I-2BR is related to effects on the glucose uptake by skeletal muscle that reduces hyperglycemia in type 1-like diabetic rats. Therefore, canavanine can be developed as effective agent to treat the diabetic disorders in the future.

Topics: Animals; beta-Endorphin; Blotting, Western; Canavanine; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Hyperglycemia; Imidazoline Receptors; Male; Protein Binding; Rats; Rats, Wistar

Rhodiola rosea (Rhodiola) is a plant in the Crassulaceae family that grows in cold regions of the world. It is mainly used in clinics as an adaptogen. Recently, it has been mentioned that Rhodiola increases plasma β-endorphin to lower blood pressure. Thus, the present study aims to investigate the antidiabetic action of Rhodiola in relation to opioids in streptozotocin-induced diabetic rats (STZ-diabetic rats).. In the present study, the plasma glucose was analyzed with glucose oxidase method, and the determination of plasma β-endorphin was carried out using a commercially available enzyme-linked immunosorbent assay. The adrenalectomy of STZ-diabetic rats was used to evaluate the role of β-endorphin. In addition, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to investigate mRNA and protein expressions.. Rhodiola-water extract dose-dependently lowered the plasma glucose in STZ-diabetic rats and this action was reversed by blockade of opioid μ-receptors using cyprodime. An increase of plasma β-endorphin by rhodiola-water extract was also observed in same manner. The plasma glucose lowering action of rhodiola-water extract was attenuated in bilateral adrenalectomized rats. In addition, continuous administration of rhodiola-water extract for 3 days in STZ-diabetic rats resulted in an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle and a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. These effects were also reversed by blockade of opioid μ-receptors.. Taken together, rhodiola-water extract improves hyperglycemia via an increase of β-endorphin secretion from adrenal gland to activate opioid μ-receptors in STZ-diabetic rats.

Topics: Adrenal Glands; Animals; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Glucose Transporter Type 4; Hyperglycemia; Hypoglycemic Agents; Intracellular Signaling Peptides and Proteins; Liver; Male; Muscle, Skeletal; Phosphoenolpyruvate Carboxykinase (GTP); Plant Extracts; Rats; Rats, Wistar; Receptors, Opioid, mu; Rhodiola; RNA, Messenger; Water

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.

Topics: Adrenal Medulla; Adrenalectomy; Animals; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Eleutherococcus; Glucosides; Hyperglycemia; Hypoglycemic Agents; Injections, Intravenous; Male; Mice; Mice, Knockout; Phenylpropionates; Phytotherapy; Rats; Rats, Wistar; Receptors, Opioid, mu; Streptozocin; Tissue Extracts

In this study aiming to clarify the relationships between beta-endorphin and glucose levels, beta-endorphin levels were determined in children in acute stress. The study was carried out on 32 critically ill children between 5 days and 12 years presenting with clinical symptoms of acute infectious conditions. 11 healthy children were taken as controls. The results showed that although beta-endorphin levels were elevated in all critically ill patients, these levels were significantly higher than control values in hyperglycaemic cases. The insulin levels were also elevated. A follow-up of nine of the hyperglycaemic cases showed a significant decline in beta-endorphin and insulin levels with recovery. Glucose tolerance was also normal. These results confirm the reports of many other studies on the role of beta-endorphin as a stress hormone.

Topics: Acute Disease; beta-Endorphin; Blood Glucose; Child; Child, Preschool; Follow-Up Studies; Humans; Hyperglycemia; Infant; Infant, Newborn; Insulin; Prognosis; Stress, Physiological

Topics: Adult; beta-Endorphin; Body Mass Index; Female; Glucagon; Glucose Clamp Technique; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Obesity

The relationship between beta-endorphin(beta-EP)/beta-lipotropin(beta-LP) and insulin secretion in the basal state and after glucose challenge was studied in obese male Zucker rats and their lean littermates. Baseline plasma beta-EP/beta-LP concentrations were similar in the two groups of animals. Baseline plasma insulin and serum glucose concentrations were significantly higher in the obese animals. Following glucose challenge, the increase in plasma beta-EP/beta-LP concentrations was significantly lower in the obese animals than in their lean littermates. Opioid blockade with naloxone failed to alter the baseline hyperinsulinemia and hyperglycemia seen in the obese animals. The data suggest that the hyperinsulinemia in the obese Zucker rat is not due to endogenous hyperendorphinemia as shown in humans with polycystic ovary syndrome. The obese rats showed dissociation between glucose-stimulated plasma levels of beta-EP/beta-LP and insulin levels which may contribute to the hyperinsulinemia and insulin resistance in these animals.

Topics: Animals; beta-Endorphin; beta-Lipotropin; Blood Glucose; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Secretion; Male; Obesity; Radioimmunoassay; Rats; Rats, Mutant Strains; Rats, Zucker

Topics: Adult; beta-Endorphin; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Islets of Langerhans; Male; Middle Aged

Intracisternal administration of synthetic human beta-endorphin to conscious, ambulatory adult male rats caused dose-related increases in plasma glucose concentration. The largest dose of beta-endorphin examined, 7.25 nmol, increased plasma glucose concentration within 7 min and this effect lasted 2.5 h. On the other hand, only 58 pmol was required to induce transient hyperglycemia, when compared to the response observed in saline-injected control rats. This hyperglycemic effect of beta-endorphin was prevented by prior systemic administration of naloxone, thus supporting the hypothesis that this beta-endorphin-induced effect is mediated at opioid receptors. beta-Endorphin also markedly increased plasma concentrations of epinephrine, norepinephrine and, to a lesser extent, dopamine. A significant positive correlation was demonstrated between plasma glucose and plasma epinephrine responses to increasing doses of intracisternally administered beta-endorphin. In addition, intracisternal beta-endorphin also increased plasma glucagon concentration without significantly increasing plasma insulin concentration. Thus, it is probable that epinephrine and glucagon are the major factors mediating this hyperglycemic effect. beta-Endorphin-induced hyperglycemia was prevented by ganglionic blockade with chlorisondamine. This further supports the thesis that intracerebral beta-endorphin increases plasma glucose concentration by activation of the central autonomic outflow. In addition to these effects on short-term regulators of glycemia, intracisternal beta-endorphin increased plasma concentrations of corticosterone and growth hormone. Both of these glucose counterregulatory hormones may play minor roles in modulating beta-endorphin-induced hyperglycemia.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Cisterna Magna; Corticosterone; Dopamine; Epinephrine; Glucagon; Growth Hormone; Hyperglycemia; Injections, Intra-Arterial; Injections, Intraventricular; Insulin; Male; Norepinephrine; Rats; Rats, Inbred Strains; Receptors, Opioid

The effect of human beta-endorphin on plasma glucose, insulin, and glucagon concentrations was studied in patients with noninsulin-dependent diabetes mellitus and in normal subjects. The subjects were divided according to their body weight into lean (body mass index, less than 25) and obese (body mass index, greater than 29.5) groups. In lean subjects, infusion of 0.5 mg/h beta-endorphin caused significant increases in peripheral plasma glucose and glucagon levels, but no change in plasma insulin. In obese subjects, there was an immediate marked increase in both plasma insulin and glucagon concentrations during the beta-endorphin infusion, but the plasma glucose response was lower than that of lean subjects. In lean diabetic patients, beta-endorphin produced significant simultaneous increments in both insulin and glucagon concentrations and significantly decreased plasma glucose levels. These hormonal responses to beta-endorphin were amplified in the obese diabetic patients. There was a significant correlation (r = 0.61; P less than 0.01) between fasting plasma glucose levels and the integrated insulin area in response to beta-endorphin. The infusion of a lower dose of beta-endorphin (0.05 mg/h) in diabetic patients produced similar increments in both insulin and glucagon levels and also decreased plasma glucose concentration. These results indicate that beta-endorphin may have important glucoregulatory effects in man depending on the dose administered, the presence of obesity, and the prevailing plasma glucose concentration.

Topics: Adult; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Endorphins; Glucagon; Humans; Hyperglycemia; Infusions, Intravenous; Middle Aged; Obesity

Topics: Animals; beta-Endorphin; Diabetes Mellitus, Type 2; Dogs; Endorphins; Glucose; Humans; Hyperglycemia; Islets of Langerhans; Stress, Physiological

Seven healthy untrained men were studied to determine if sustained hyperglycemia is a stimulus to enhanced plasma levels of beta endorphin (beta-EP) and if so whether prior exercise affects that enhancement. After an overnight fast hyperglycemic glucose clamps were performed on 3 separate days: after prior rest, 2 h after exercise, and 48 h after exercise. Subjects exercised on a bicycle ergometer for 1 h at 150 W (64% VO2 max). Plasma glucose concentration was elevated in 4 continuous sequential stages to 7, 11, 20 and 35 mM with each stage lasting 90 min. Plasma glucose concentrations did not differ for each subject across the three clamps. beta-EP immunoreactivity was measured in arterialized venous blood samples using a specific and sensitive radioimmunoassay. Resting beta-EP at basal glucose concentrations was 3.8 +/- 0.7 fmol X ml-1 (mean +/- se) and prior exercise either 2h (3.2 +/- 0.5 fmol X ml-1) or 48 h (4.3 +/- 0.7 fmol X ml-1) before a clamp study did not effect these levels, (p greater than 0.05). At no time during the 3 hyperglycemic clamps did plasma levels of beta-EP differ significantly from resting values. At the highest level of hyperglycemia (35 mM) beta-EP was 3.1 +/- 0.2, 4.9 +/- 0.6 and 4.8 +/- 0.7 fmol X ml-1 in the resting, 2h and 48 h post exercise clamp studies respectively. The significance of these data is that this lack of a response is in distinct contrast to elevations of this peptide found during hypoglycemic states. We conclude that sustained hyperglycemia is not a stimulus to enhanced secretion of beta-EP into plasma and this lack of a response is not effected by prior exercise.

Topics: Adult; beta-Endorphin; Endorphins; Hematocrit; Humans; Hydrocortisone; Hyperglycemia; Male; Physical Exertion

The present study was designed to investigate the in vivo effects of beta-endorphin on plasma levels of glucagon, insulin and glucose in rabbits, and to elucidate some of the mechanisms involved. beta-Endorphin (50 micrograms) injected intravenously into fasted rabbits, decreased plasma levels of insulin (-4.5 +/- 1.3 microU/ml, P less than 0.05) and increased plasma levels of glucose (+2.7 +/- 0.4 mmol/l, P less than 0.05). Similar hypoinsulinemic and hyperglycemic effects were observed for 25 and 2.5 micrograms beta-endorphin in fasted and 50 and 0.5 micrograms beta-endorphin in fed rabbits. beta-Endorphin produced slight and transient increases in plasma levels of glucagon at the highest dose in fed rabbits, only (+80 +/- 9 pg/ml, P less than 0.05). The beta-endorphin-induced hypoinsulinemia was not inhibited by phentolamine, yohimbine, propranolol or atropine, which is in consistency with a direct inhibitory effect of beta-endorphin on the beta-cell in rabbits. The beta-endorphin-induced hyperglycemia was reduced by naloxone (+0.8 +/- 0.1 mmol/l) but not by N-methyl-naloxone (ORG 10908) a peripheral opiate receptor blocking drug (+2.2 +/- 0.2 mmol/l), suggesting a central nervous action on opiate receptors. This central action of beta-endorphin was probably not mediated by catecholamine release or other stimulation of adrenergic or muscarinic receptors, since the beta-endorphin-induced hyperglycemia was not inhibited by phentolamine, yohimbine, propranolol or atropine. These results suggest that the beta-endorphin-induced hyperglycemia was caused, at least in part, by a peripheral inhibition of insulin release and a central stimulation on glucoregulation.

Topics: Animals; Atropine; beta-Endorphin; Blood Glucose; Endorphins; Female; Glucagon; Hyperglycemia; Injections, Intravenous; Insulin; Naloxone; Phentolamine; Propranolol; Quaternary Ammonium Compounds; Rabbits; Yohimbine

Three experiments were designed to study the changes in brain biogenic amines, beta-endorphin and insulin in response to hyperglycemia in adult male rats. In all three experiments, animals were decapitated 10 minutes post injection (IP) of either 2.5 ml of 40% glucose or 0.9% saline. In the first experiment brain DA, NE, 5-HT and 5-HIAA were measured using fluorometric method. Plasma glucose, insulin (RIA) and corticosterone (CPB) were also determined. In addition to these measurements, brain beta-endorphin was determined (RIA) in the second experiment and brain insulin (RIA) in the third experiment. In all three experiments the hyperglycemic groups showed a significant increase in plasma insulin, brain NE and 5-HT and a significant decrease in brain 5-HIAA and no significant change in plasma corticosterone, brain DA, beta-endorphin and insulin. The results obtained in these experiments suggest that high levels of glucose may have an inhibitory effect on the metabolism of NE and 5-HT resulting in increases in the level of both amines. They also suggest that brain insulin is independent of the pancreatic one since high blood glucose did not influence the central level.

Topics: Animals; beta-Endorphin; Biogenic Amines; Brain Chemistry; Dopamine; Endorphins; Hydroxyindoleacetic Acid; Hyperglycemia; Insulin; Male; Norepinephrine; Rats; Rats, Inbred Strains; Serotonin

Intermittent inescapable foot shock stress for 1 hour elicited significant hyperglycemia in mice. Pretreatment with the long acting narcotic antagonist naltrexone (1.0 mg/kg, 1 hr prior to stress) prevented stress hyperglycemia. Naltrexone did not affect blood glucose in unstressed control mice. These findings suggest the involvement of endogenous opioids in the hyperglycemic response to stress in mice. The possible mode of interaction of endorphin in stress hyperglycemia is discussed.

Topics: Animals; beta-Endorphin; Blood Glucose; Endorphins; Hyperglycemia; Male; Mice; Mice, Inbred BALB C; Naltrexone; Stress, Physiological