Combined effect of adenosine,alpha adrenergic and adenosine antagonists on serum insulin and insulin secretion from rat pancreatic islets

• 1.1. The effect of adenosine separately or in combination with alpha-1 adrenergic antagonist prazosin and alpha-2 adrenergic antagonist yohimbine as well as adenosine antagonists 8-phenyltheophylline and xanthine amine conjugate on glucose-induced insulin secretion from isolated rat pancreatic islets was studied.
• 2.2. Their in vivo effects on serum glucose and insulin levels were also investigated. Adenosine at 10 and 100 μM inhibited significantly, insulin secretion from the isolated islets whereas at 10 mM slightly increased the secretion of insulin.
• 3.3. Prazosin used at 100 μM inhibited insulin secretion. When it combined with adenosine (10 μM) it augmented the inhibitory effect of adenosine.
• 4.4. In vivo prazosin (21 mg/kg bodywt) caused a hyperglycaemia which was accompanied by hypoinsulinaemia.
• 5.5. Concurrent administration of this drug with adenosine neither affect the hyperglycaemic nor the hypoinsulinaemic effects of adenosine.
• 6.6. On the other hand, yohimbine (100 μM) has no effect neither separately nor in combination with adenosine (10 μM) in modulating the inhibitory effect of adenosine on insulin secretion.
• 7.7. When Yohimbine administered at 19.5 mg/kg body wt it did not alter serum glucose but it markedly increased the serum insulin level. Its combined administration with adenosine reduced the hyperglycaemic effect of adenosine with a remarkable increase in serum insulin.
• 8.8. Both adenosine-antagonists were ineffective in alteration of insulin secretion.
• 9.9. However, combination of 8-phenyltheophylline with adenosine (10 μM) totally blocked the inhibitory effect of adenosine on insulin secretion while xanthine amine conjugate failed to prevent this effect of adenosine.
• 10.10. These results indicate that the inhibitory effect of adenosine on insulin secretion is neither mediated via alpha-1 nor alpha-2 adrenoceptors. It might be via activation of specific adenosine receptors on rat islets which are sensitive to blockade by 8-phenyltheophylline.

     

Increased muscle glucose uptake in response to chronic glyburide treatment is not related to changes in glucose transporter (GLUT4) protein

• 1.1. The mechanism of action of glyburide (a sulfonylurea) on muscle has been investigated by measuring glucose uptake and glucose transporter (GLUT4) protein levels after chronic glyburide treatment.
• 2.2. A dietary induced insulin resistant rat model (4 wk of high-fat, high-sucrose feeding) was given glyburide (2mg/kg/day) for 10 days and glucose uptake was measured in a perfused hindquarter preparation.
• 3.3. Protein levels of the GLUT4 glucose transporter were determined by Western analysis.
• 4.4. After 7 days of treatment, rats fed glyburide had lower blood glucose concentrations 2 hr (72 ± 5 vs 103 ± 12 mg/dl) and 24 hr (97 ± 7 vs 123 ± 7 mg/dl) after glyburide administration with no difference in serum insulin levels compared to vehicle treated animals.
• 5.5. Glucose uptake was approx doubled in basal state (0 insulin) in response to glyburide (2.8 + 0.4 vs 1.7 ± 0.2μ mol/g per hr).
• 6.6. Maximal insulin (100 nM) stimulated glucose uptake tended to be higher in the glyburide treated group, but did not reach statistical significance (8.0 ± 0.7 vs 7.0 ± 0.6 μmol/g per hr).
• 7.7. Western analysis revealed no significant effect of glyburide on the GLUT4 protein level in skeletal muscle.
• 8.8. These results suggest that glyburide alters glucose uptake through some mechanism other than alterations in the level of the GLUT4 glucose transporter protein.

     

Variations in tissue reserves,plasma metabolites and pancreatic hormones during fasting in immature carp (Cyprinus carpio)

• 1.1. Immature carp were subjected to 2-month fasting periods. Mobilization of reserves in liver and muscle, and the energy contribution of each reserve were studied. Changes in plasma glucose, amino acids, insulin and glucagon levels were determined throughout the experiment.
• 2.2. No changes were observed in plasma glucose, insulin or glucagon at 19 days of fasting, but plasma amino acids increased. At 50 days of fasting, both plasma glucagon and amino acids increased, liver glycogen decreased and muscle proteolysis began.
• 3.3. Between 50 and 67 days of fasting, plasma glucose and insulin decreased significantly, while glucagon and amino acids continued to increase. Strong muscular proteolysis was observed while liver glycogen stabilized.
• 4.4. The contribution of each reserve in liver and muscle to energy production throughout fasting is considered.

     

A comparative study of glucose metabolism between the camel (Camelus dromedarius) and the sheep (Ovis aries)

• 1.1. Glucose entry rate was measured in two camels (Camelus dromedarius) and two sheep (Ovis wies) in the fed state and also after 72 hr of fasting.
• 2.2. Plasma glucose concentration in the fed camels (129 mg/100 ml) was considerably higher than that of the fed sheep (63 mg/100 ml).
• 3.3. The mean glucose entry rate in the fed camels (1.67mg/min per kg body wt) was very similar to the sheep (1.79 mg/min per kg body wt).
• 4.4. When the results were expressed as a function of the metabolic body size, the entry rates in the camel were 1.5 times greater than that of the sheep.
• 5.5. The relationship between glucose entry rate and plasma glucose concentration in different mammalian species is discussed.

     

Fetal lung metabolism: Response to maternal fasting

• 1.1. Fetal lung metabolic response to maternal fasting late in gestation was investigated.
• 2.2. Maternal fasting 4 days before term was associated with low fetal plasma glucose and insulin levels but increased levels of fetal plasma glucagon, glycerol, lactate and fatty acids.
• 3.3. Fetuses from fasted mothers showed a significant decrease in body weight (30%), lung weight (30%) and lung glycogen (46%), but no change in lung protein, phospholipid or total lung DNA, suggesting that lung size is affected more than maturation.
• 4.4. Fetal lung slices incubated in vitro showed that lactate oxidation to CO₂ equalled that of glucose in control fetal lungs and was unaffected by maternal fasting, while glucose oxidation was depressed (23%).
• 5.5. Maternal fasting significantly decreased in vitro incorporation of [U-¹⁴C]-glucose, [U-¹⁴C]lactate and [1-¹⁴C]palmitate into lung phospholipids.
• 6.6. Fetal lungs from fasted mothers showed increased conversion of lactate to glucose, indicating gluconeogenic potential by fetal lung.
• 7.7. These studies show that plasma lactate serves as an important energy fuel and substrate for lipid synthesis for the fetal lung, and maternal fasting markedly alters fetal lung metabolism.

     

Effects of streptozotocin-diabetes and l-thyroxine treatment on TSH and GH,and circulating glucose and glycerol in thyroidectomized rats

• 1.1.The response to exogenous thyroxine in thyroidectomized rats made diabetic by treatment with streptozotocin was greatly impaired, as shown by their growth retardation and the lack of increase in plasma GH and pituitary GH and TSH concentrations.
• 2.2.Insulin administration partially compensated for these endocrine alterations in diabetic thyroidectomized rats. When these animals received enough exogenous thyroxine to normalize their plasma PBI and TSH levels, insulin administration did not decrease their augmented glucose and glycerol concentrations.
• 3.3.These findings show the permissive action between thyroid hormones and insulin although some effects of the former counteract those of insulin.

     

Amino acid accumulation in kidney cortex of lambs and piglets as affected by insulin

• 1.1. Insulin stimulated intracellular accumulation of α-amino-isobutyric acid (AIB) in kidney cortex slices from young lambs and piglets.
• 2.2. The effect was similar in the absence or presence of glucose.
• 3.3. The induction of the stimulatory effect on renal AIB transport was blocked by cycloheximide. an inhibitor of protein synthesis.
• 4.4. The insulin stimulation of intracellular AIB accumulation is due to an increased influx and not to a reduced efflux of AIB.
• 5.5. Analysis of transport kinetics for AIB showed that insulin increased V_max but did not change K_m.
• 6.6. It is concluded that insulin stimulates uptake of certain neutral amino acids into kidney cortex cells in young animals.
• 7.7. The effect on renal amino acid transport appears to be mediated through increased synthesis of a membrane carrier.

     

2-Deoxyglucose transport by the frog sartorius: Effects of electrical stimulation and N-carbobenzoxy-glycyl-l-phenylalaninamide

• 1.1. Studies characterizing glucose transport in the frog sartorius were performed.
• 2.2. For nonstimulated and stimulated muscles, intracellular 2-deoxyglucose exceeded 2-deoxyglucose-6-phosphate at 15 min, showed little further increase, and was maintained below the extracellular concentration for 2 hr.
• 3.3. Accumulated 2-deoxyglucose-6-phosphate did not inhibit glucose transport.
• 4.4. Unlike in adipocytes, basal and stimulated 2-deoxyglucose transport showed no difference in sensitivity to N-carbobenzoxy-glycyl-l-phenylalaninamide.
• 5.5. Phenylarsine oxide blocked contraction-enhanced 2-deoxyglucose uptake.
• 6.6. These results suggest that the glucose transporter of the sartorius exhibits auto-regulation, and that basal transport is not regulated by the same process as in adipocytes.

     

Changes in plasma glucose and lipid concentrations during treadmill exercise in domestic fowl

• 1.1. Plasma glucose, non-esterified fatty acid, triglyceride, cholesterol and lactate concentrations were measured during 90 min treadmill exercise at a work intensity of 55–60% maximum.
• 2.2. After 90 min exercise plasma glucose fell by 35% whilst the non-esterified fatty acid concentration rose to as much as 3–4 times resting.
• 3.3. Exercise had no significant effect on plasma cholesterol, triglyceride or lactate concentrations.
• 4.4. The findings indicate a progressive increase in fat utilization during prolonged exercise. Possible hormonal mechanisms underlying exercise-induced changes in lipid and carbohydrate metabolism are discussed.

     

Blood volume recovery in hemorrhaged japanese quail

• 1.1. Blood volume and plasma biochemical changes and feed and water consumption in response to a hemorrhage by phlebotomy of 30% of the calculated total blood volume with and without replacement of blood volume with physiological saline were determined in juvenile male Coturnix coturnix japonica.
• 2.2. Plasma protein and osmolality decreased rapidly posthemorrhage and did not recover by 72 hr posthemorrhage.
• 3.3. Plasma glucose, Na⁺ and K⁺ increased within Ihr postphlebotomy. Plasma Na⁺ returned to nonphlebotomized levels within 6 hr postphlebotomy.
• 4.4. Saline replacement of blood volume resulted in hypervolemia within 3–5 min postphlebotomy.
• 5.5. Phlebotomized quail receiving no saline recovered blood volume to 0 hr (nonphlebotomized) levels within l hr postphlebotomy.

     

Characterization of the blood volume and iron kinetics in the three-toed sloth,Bradypus tridactylus

• 1.1. Blood volume and iron kinetics were determined in three specimens of Bradypus tridactylus which were obtained in the coastal north-east regions of Brazil.
• 2.2. The average blood volume, circulating red cell volume and plasma volume were 54.9, 19.5 and 35.4 ml/kg body weight, respectively.
• 3.3. The average plasma iron disappearance half-time was 150.6min; the red cell radioiron uptake was 62% and the serum iron was 74.3 μg/100 ml.
• 4.4. From these figures the plasma iron turnover rate was calculated to be 165.6 μg/kg per day and the red cell iron turnover rate 102.7 μg/kg per day.

     

Effects of insulin on the fatty acid composition of the total blood plasma lipids in the european EEL,Anguilla anguilla L

• 1.1. The fatty acid composition of plasma total lipids in the European eel, Anguilla anguilla L., was studied 3, 10, 24, 96, 168 and 336 hr after i.p. injection of bovine insulin (100 i.u./kg body wt) dissolved in glycine-NaOH buffer solution. Control eels were treated by buffer solution only.
• 2.2. The insulin-treated eels showed an elevated percentage of palmitoleic acid (16:1) 3 and 336 hr post-injection compared to buffer-treated control eels.
• 3.3. Insulin caused a significant decrease in the percentage of oleic acid (18:1) 336 hr post-injection.
• 4.4. Besides the observations mentioned above insulin was not found to have any pronounced effects on the fatty acid composition of total blood plasma lipids.

     

Aerobic glucose disposal in the oyster: An in vivo kinetic analysis

• 1.1. Aerobic glucose disposal in starved oysters exposed to 1 mM external glucose was 2.29 μg C/g wet wt/min.
• 2.2. It was hypothesized that the maximum disposal rate is limited by the maximum rate of transepithelial glucose transport.
• 3.3. The major recipients of glucose-carbon were glycogen and amino acids. 4. The rate of glucose-carbon disposal to these two pools was 0.80 and 0.42 μg C/g/min, respectively.
• 4.5. The internal energy state determines the pathways of glucose disposal.
• 5.6. Disposal of glucose-carbon in “glucose-primed” oysters is primarily into glycogen.
• 6.7. In fasted bivalves the disposal is primarily into amino acids and carboxylic acids.
• 7.8. The uptake of dissolved glucose has the potential of contributing significantly to growth under conditions where the external glucose concentration is kept artificially high.

     

Physiological responses to exercise and hypoglycaemia stress in pigs of differing adrenal responsiveness

• 1.1. Twelve Large White × Landrace male pigs, six with high adrenocortical response to ACTH, and six with low response, were subjected to mild and moderate exercise, and then to insulin-induced hypoglycaemia.
• 2.2. Plasma ACTH, cortisol, catecholamines and some haematological and plasma biochemical parameters were determined in response to exercise, and glucose and cortisol in response to insulin challenge.
• 3.3. High responders had significantly greater increases than low responders in ACTH, cortisol and catecholamines following exercise, and in cortisol following insulin challenge.
• 4.4. The results suggest that differences in adrenocortical response to exogenous ACTH are an accurate reflection of the animal's response to stressful stimuli.

     

Specificity of the permissive effect of d-Glucose on insulin release in chicken pancreas

• 1.1. As previously shown, 14 mM d-glucose, a non-insulinotropic concentration in isolated chicken pancreas, permits an insulin release in response to d-glyceraldehyde, (d-GA; a glycolytic fuel) and l-leucine or α-ketoisocaproic acid (α-KIC) (non-glycolytic fuels), which alone are not initiators of insulin release in this species.
• 2.2. The “permissive” effect of d-glucose was also observed in the presence of d-mannose (which, as shown herein, is not insulinotropic alone).
• 3.3. The specificity of glucose for this “permissive” effect was, therefore, subsequently questioned in the presence of 10mM α-KIC by substituting various glycolytic and non-glycolytic fuels to glucose.
• 4.4. d-GA (at 5 and 15mM), d-mannose (30 and 50 mM), or the association of l-glutamine + l-asparagine permitted an insulin release in response to α-KIC.
• 5.5. The response was, however, delayed with d-GA, only occasionally with 50 mM d-mannose, and required high concentrations and was delayed in the presence of l-glutamine + l-asparagine as compared to that obtained with 14mM d-glucose + α-KIC.
• 6.6. In conclusion, the threshold of fuel-induced insulin release is much higher in the chicken than in mammals and this threshold is most efficiently lowered by glucose.

     

Flight-induced increase in circulating levels of melatonin in the homing pigeon

• 1.1. Homing pigeons, receiving regular flight-training for participation in racing competitions, were flown from their usual release site, 48 km away from “home”.
• 2.2. On their return “home” within 60–80 min, blood samples for the measurement of melatonin were taken within 1–3 min of arrival.
• 3.3. Post-flight circulating levels of melatonin were found to be about 82% higher than those of the resting control pigeons without any change in plasma osmolality.
• 4.4. This daytime increase in circulating levels of melatonin suggests that melatonin, by virtue of its known hypothermic effect of facilitating peripheral heat dissipation, could prevent excessive flight-induced hyperthermia.
• 5.5. It is also suggested that the flight-induced increase in plasma levels of melatonin is consistent with the known analgesic and metabolic effects of the hormone.

     

Evidence that protein kinase C is involved in regulating glucose transport in the adipocyte

• 1.1. The role of protein kinase C in the mechanism of stimulation of glucose transport in rat adipocytes was investigated.
• 2.2. Glucose transprt was stimulated by dioleoylglycerol (DOG), tetradecanoyl phorbol acetate (TPA) and phospholipase C (PLC).
• 3.3. Agents that inhibit protein kinase C (polymyxin B, gossypol and quercitin) also inhibited glucose transport that had been stimulated by DOG, TPA, PLC and insulin.

     

Activation and inhibition of insulin receptor autophosphorylation by trypsin treatment of intact H35 cells

• 1.1. Treatment of intact cultured H35 cells with trypsin (1 mg/ml) for 15 min at low temperature (4°C) or for 30 sec at 37°C causes activation of the insulin receptor subsequently isolated from the cells.
• 2.2. Receptor activation was assessed by increased phosphotyrosine content of the β-subunit of the receptor, and increased autophosphorylation using [³²P]-ATP.
• 3.3. Treatment of the cells for 15 min at 37°C however completely abolished insulin binding and all insulin receptor kinase activity.
• 4.4. These data demonstrate that proteolytic damage of the extracellular domain of the insulin receptor can render the receptor kinase inactive and lead to a cell which is unresponsive to insulin.

     

The chemical composition of the follicular fluid of the teleost Clinus dorsalis (Perciformes: Clinidae)

• 1.1. The osmolarity and pH of the follicular fluid was determined and analyses of total glucose, total lipids, total proteins, amino acids, urea, sodium and potassium carried out.
• 2.2. The mean osmolarity of the follicular fluid was found to be 325 mOsm/kg and the mean pH was 7.9.
• 3.3. The embryotrophe was rich in lipids (1092.39 mg/100 ml) and amino acids with the amino acid concentration exceeding normal values for human plasma.

     

Flight effects on certain blood parameters in homing pigeons Columba livia

• 1.1. Various blood parameters were monitored in resting and flown homing pigeons. A homing flight of 48 km lasting 60–80 min did not significantly alter plasma levels of total protein, electrolytes and plasma osmolality, which indicated maintenance of the homeostatic stability of the internal milieu during moderate exercise.
• 2.2. Plasma concentrations of marker enzymes such as alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), laetate dehydrogenase (LDH) and creatine phosphokinase (CPK) that tend to denote muscle damage and metabolic flux in prolonged exercise, were also not altered, thereby indicating the steady state of tissue structure and function during a flight of this magnitude.
• 3.3. Significant increases in plasma levels of uric acid and creatinine and decreases in plasma albumin were observed in the flown pigeons.
• 4.4. The flight-induced increase in blood uric acid could be attributed to increased purine catabolism and the increase in creatinine to increased nucleotide turnover.
• 5.5. It is suggested that the higher uric acid levels should not only enhance water conservation, but may also reduce flight-induced hyperthermia besides acting as an antioxidant defence against oxidative tissue injury.
• 6.6. The rise in creatinine is indicative of the breakdown of phosphocreatine for energy during the initial period of flight prior to the utilization of carbohydrate and lipid as fuels.
• 7.7. The decrease in plasma albumin should account for the albumin as lipid carrier lost in transport to the muscles during flight.