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Biomedical subjects

D L Curry

Publications and source records attributed to D L Curry.

At least 55 records · Page 3Linked to original sources
PubMed1985

Dynamics of insulin and glucagon release in rats: influence of dietary manganese.

The effect of manganese on endocrine pancreatic function was examined in manganese-sufficient (control) and manganese-deficient (Mn-) Sprague-Dawley rats. Pancreatic insulin release was lower (P less than 0.05) in Mn- rats than in controls in response to both a 300 mg/dl and a 100 mg/dl glucose stimulus. The 300 mg/dl glucose stimulus induced the synthesis of 19.4 micrograms insulin/g pancreas in control rats. Additionally, no appreciable intracellular degradation of insulin occurred over an 80-min perfusion period. By contrast, in Mn- rats, there occurred an intracellular insulin degradation amounting to 7.8 micrograms/g pancreas. This enhanced degradation was partially compensated by a net insulin synthesis of only 3.4 micrograms insulin/g pancreas. Initial (min 1-3) insulin release by Mn- rats in response to 10 mM arginine was lower (P less than 0.05) than that observed in controls. Pancreatic glucagon release in response to 10 mM arginine was not affected by manganese deficiency. These findings demonstrate that manganese deficiency results in depressed pancreatic insulin synthesis and enhanced degradation. These factors may be responsible for the abnormal carbohydrate metabolism observed in Mn- animals.

Animals↗
PubMed1984

Effect of manganese deficiency on insulin secretion and carbohydrate homeostasis in rats.

The effects of manganese (Mn) deficiency on carbohydrate metabolism in the Sprague-Dawley rat were investigated. Oral glucose tolerance tests were performed on offspring from Mn-sufficient female rats fed 45 micrograms Mn per gram diet (C-C), offspring from Mn-deficient female rats fed 1 microgram Mn per gram diet (D1-D1) and rats not exposed to Mn deficiency in utero but fed D1 diet from weaning to maturity (D1). Mn-deficient rats, D1 and D1-D1, had significantly lower concentrations of Mn in liver, kidney, heart and pancreas than controls. D1-D1 rats responded with a diabetic type of glucose tolerance curve when given oral glucose. Insulin levels of D1-D1 rats were not commensurate with their high glucose levels. Measurements made by using an isolated perfused-pancreas preparation indicate that insulin output due to release of stored hormone was 76% of control levels in D1-D1 rats. This suggests either lower insulin stores or impaired release of insulin in D1-D1 rats. Second phase insulin release was also significantly lower in D1-D1 rats than in controls. Pancreatic insulin content was 63% of control levels in D1-D1 rats, further supporting the idea of lower insulin stores in Mn-deficient rats. No differences in plasma glucose levels were observed between D1 rats and controls after an oral-glucose load. These findings indicate that dietary Mn deficiency can result in impaired insulin secretion producing impaired carbohydrate metabolism; however, the timing of the deficiency may be a critical factor in the expression of this abnormality.

Animals↗
PubMed1984

Glucose-induced insulin secretion by perfused pancreas of 2- and 12-mo-old Fischer 344 rats.

Previous studies have shown that cells from older Sprague-Dawley rats secrete insulin less efficiently in response to a maximal glucose challenge than do beta-cells from young animals. In the current study we have asked whether this change in beta-cell response occurs in another strain of rat, and, if so, whether the secretory defect occurs at submaximal as well as maximal glucose stimulatory levels. Pancreas perfusions were carried out on 2- and 12-mo-old Fischer 344 rats at perfusate glucose concentrations of 150 and 300 mg/dl. The secretory data for each pancreas was subsequently corrected for differences in islet cell mass and expressed as insulin secretion per unit islet cell. The results show that 12-mo-old Fischer rats release more insulin per total pancreas than do 2-mo-old animals at both glucose concentrations. However when corrected for islet cell mass, the amount of insulin secretion per islet cell is actually reduced in the older Fischer rat. These data are comparable to those seen previously in the 12-mo-old Sprague-Dawley rat and indicate that the insulin secretory defect seen as rats grow older is not species specific.

Aging↗
PubMed1984

Reflex inhibition of insulin secretion: vagus nerve involvement via CNS.

The in situ brain-pancreas experimental model was used to investigate the influence of the vagus nerve during tonic direct central nervous system (CNS) inhibition of insulin secretion. Tonic CNS inhibition of insulin secretion was partially and transiently reversed following bilateral cervical vagotomy, suggesting that this inhibition includes a vagally mediated component. However, a substantial CNS inhibition of insulin secretion still occurred in the vagotomized preparations. This demonstrates that a major component producing tonic CNS inhibition of insulin secretion is independent of the vagus nerve and, furthermore, that it must be via direct sympathetic efferent pathways to the pancreas (because these preparations are functionally parasympathectomized via vagotomy). Further investigation into the vagus nerve involvement was carried out by stimulating either the afferent (central) or efferent (pancreatic) cut end of the vagus nerve of bilaterally vagotomized brain-pancreas preparations. Stimulation of the efferent vagus did not appreciably alter the effect of vagotomy on insulin secretion. However, when the central cut vagus was stimulated, the early transient reversal of tonic inhibition, which occurred in the vagotomized preparations, was totally reversed. This suggests that the vagally mediated early transient component of tonic CNS inhibition of insulin secretion is via afferent (central) neurons in the vagus nerve. These data demonstrate a reflex pathway for inhibition of insulin secretion that is comprised of vagal afferent neurons, the CNS, and sympathetic efferent neurons ending directly on the islets of Langerhans. It is tempting to speculate that gastrointestinal receptors exist that are capable of initiating this reflex inhibition of insulin secretion.

Animals↗
PubMed1984

Magnesium requirement for somatostatin inhibition of insulin secretion.

Rat pancreas perfusions were performed using a perfusate with a fixed calcium concentration of 5 mEq/l and magnesium varying from 0 to 0.6 mEq/dl. Insulin secretion was stimulated by a constant glucose infusion of 300 mg/dl. This glucose concentration produces the typical biphasic insulin secretory response. We observed that in the absence of magnesium, somatostatin concentrations of 0.5 and 2.0 ng/ml were without effect on first phase insulin secretion. However, these same somatostatin levels produced 50% or more inhibition of insulin secretion in the presence of magnesium at 0.3 or 0.6 mEq/l. Similarly, in the absence of magnesium, somatostatin at 50 ng/ml failed to inhibit second phase insulin secretion, whereas this same somatostatin level produced about 50% inhibition of insulin secretion in the presence of magnesium at 0.3 mEq/l. Thus, altering perfusate magnesium concentrations without changing calcium is an important determinant of the degree of inhibition of secretion produced by somatostatin. In particular, in the absence of magnesium ion, somatostatin concentrations which would 'normally' produce 50% inhibition of secretion (ID50) are without effect. Therefore, magnesium ion is necessary for the full inhibitory effect of somatostatin to occur. These results suggest that inhibitors, as well as potentiators, of the insulin secretory process may act by altering intracellular/membrane calcium-magnesium ratios, but in opposite directions.

Animals↗
PubMed1983

Effects of paraquat on plasma glucose, cortisol, catecholamines, and insulin in the beagle.

Paraquat is known to produce hyperglycemia in rodents, although the mechanisms responsible for the hyperglycemic effect of paraquat are not clearly understood. In this study we report the effects of paraquat (25 mg/kg iv) on plasma glucose, cortisol, catecholamines, and insulin in dogs. Paraquat caused a significant increase in plasma glucose level at all times of measurement except at 0.5 hr following paraquat administration. The cortisol levels after paraquat treatment were increased to 133, 305, 279, 418, 517, 672, and 567% above zero time control at 0.5, 1.5, 3, 6, 12, and 24 hr, and at death time respectively. The catecholamines at these times were increased to 42, 17, 72, 118, 138, 226, and 435% above the control. In contrast to cortisol and catecholamines, the plasma insulin levels after paraquat treatment were significantly decreased at 3, 6, 12, and 24 hr. These hormonal observations can explain, at least in part, the observed hyperglycemia, since all promote hyperglycemic states. For example, cortisol is gluconeogenic, catecholamines are glycogenolytic, and lower insulin levels result in depressed peripheral glucose utilization.

Animals↗
PubMed1983

Direct tonic inhibition of insulin secretion by central nervous system.

An experimental animal model was developed to investigate the influence of the central nervous system (CNS) on insulin secretion via direct innervation to the pancreas. This model eliminates any indirect CNS effect on the pancreas by hormonal factors. It consists of a vascularly isolated, in situ perfused rat pancreas preparation with the cephalic portion of the animal functional, including innervation to the pancreas. Using this rat model, we have demonstrated that the nonstimulated rat brain exerts a tonic inhibition of glucose-stimulated insulin secretion in nonfasted rats. This inhibition can only occur directly via neurons from brain to pancreas, probably via the sympathetic nervous system. The brain does not alter the biphasic pattern of insulin secretion, but it suppresses the overall insulin secretory process throughout both phases of insulin secretion by a relatively constant degree ranging from 38 to 47%. The physiological purpose of this tonic suppression of insulin secretion is open to speculation, but it is well known that tonic sympathetic stimulation of the cardiovascular system represents an important physiological control mechanism. An analogous control may exist with respect to insulin secretion.

Adrenal Glands↗
PubMed1982

Dynamics of insulin and glucagon secretion by the isolated perfused cat pancreas.

1. The dynamics of insulin and glucagon secretion by the isolated perfused cat pancreas was studied in response to glucose and amino acid stimuli. 2. Insulin secretion is biphasic in response to either glucose or amino acid stimuli. 3. Glucose caused a much more pronounced first phase release than did a complete amino acid mixture; whereas glucose and the amino acid mixture stimulated late second phase insulin secretion equipotently. 4. The same amino acid mixture produced a biphasic secretion of glucagon characterized by a rapid and transient spike-release which was followed by a substantial, relatively steady-state, second secretory phase. 5. Various combinations of glucose and amino acids resulted in insulin secretion which suggests a simple additive stimuli phenomenon; whereas no such additive effect was observed with respect to amino acid stimulation of glucagon secretion. 6. Instead, various of the amino acids appear to stimulate maximal glucagon secretion independently. 7. Glucose failed to cause a suppression of amino acid induced glucagon release. 8. The quantitative aspects of this study suggest that the cat pancreas is very responsive to amino acid modulation of hormone release, a fact which may well reflect the high amino acid content of the cat's diet.

Amino Acids↗
PubMed1981

Ethanol-insulin interrelationships in the rat studied in vitro and in vivo: evidence for direct ethanol inhibition of biphasic glucose-induced insulin secretion.

The effect of ethanol (ETOH) on glucose-stimulated insulin secretion was studied using: (1) an in vitro isolated pancreas perfusion system, and (2) an in vivo preparation utilizing unrestrained, unanesthetized rats with indwelling jugular and aortic catheters. ETOH exposure in vitro resulted in a decrease in glucose-stimulated insulin secretion from the perfused rat pancreas. Second phase secretion (min 30-60) was inhibited at low ETOH exposure (100 mg/dl) and both first (min 2-8) and second phase secretion were inhibited at higher ETOH levels (1000 mg/dl). This indicates that second phase secretion of insulin from the pancreas is more sensitive to the acute effects of ETOH than is first phase secretion. ETOH preinfusion of 4 hr in vivo resulted in an approximate 20 mg/dl decrease in plasma glucose concentrations with little or no alteration in plasma insulin levels. One hour ETOH preinfusion produced a modest 8 mg/dl fall in plasma glucose. Intravenous glucose tolerance tests following low level ETOH infusion of 4 hr resulted in an enhancement in the insulin response with no change in glucose removal. This enhancement was not observed at higher ETOH levels or after high-level, short (1 hr) ETOH preinfusion. The data suggest that stimulus-induced insulin secretion may be enhanced by an ETOH metabolite if the ETOH exposure is prolonged and at a low level. Higher ETOH concentration appears to directly block this enhancement. Due to response similarities the rat model may be of considerable value to study the effects of ETOH on stimulus-induced insulin secretion in human subjects.

Animals↗
PubMed1980

Kinetics of insulin clearance by the liver in perfused liver-pancreas.

The relationship between hepatic insulin extraction velocity and portal plasma insulin concentration was assessed using in situ perfused liver-pancreas preparations from rats fasted 24 or 48 hours. During hepatic transit of the first phase of glucose-stimulated insulin secretion, hepatic extraction velocities followed first order kinetics for all insulin concentrations observed (less than 1 to 17 ng/ml). During the second phase of insulin release, saturation of the insulin removal process occurred at insulin concentrations between 12 and 14 ng/ml. At non-saturating insulin levels, livers from rats fasted 24 hours clear insulin at about 4.0 ml/min corresponding to an extraction ratio of 52%. In contrast, livers of liver-pancreases from 48 hour fasted rats clear insulin at 2.4 ml/min with an extraction ratio of 31%.

Animals↗
PubMed1979

Effect of fasting on insulin removal by liver of perfused liver-pancreas.

Using in situ perfused rat liver-pancreas preparations, the hepatic clearance of biphasically released endogenous insulin was studied using livers of fed and fasted rats. Hepatic insulin extraction was determined by subtracting the mean endogenous insulin output found in the posthepatic vena cava effluent of liver pancreas preparations from the amount of insulin found in the prehepatic portal effluent of perfused pancreas preparations. All pancreas perfusions and liver-pancreas perfusions were subjected to the same plasma glucose stimulus (250 mg/dl) for 40 min. In the fed state, no significant hepatic extraction of insulin occurred. The biphasic pattern of insulin appearance in the posthepatic vena cava effluent, which ranged from less than 1 to 21 ng/ml, was unaffected by passage through the liver. In contrast, when rats were fasted for 24 h, approximately 50% of the insulin released into the portal vein was removed by their livers during one transhepatic passage. After a 48-h fast, insulin extraction capacity decreased relative to the capacity observed for livers of 24-h fasted rats.

Animals↗
PubMed1977

Magnesium modulation of glucose-induced insulin secretion by the perfused rat pancreas.

Increasing levels of magnesium were found to cause a marked depression of glucosestimulated insulin secretion at fixed calcium levels, particularly at levels which bracketed the concentration of ultrafiltrable magnesium found in normal rat plasma (1.3 meq/l), i.e., increasing magnesium from 0.6 to 1.2 meq/l depressed secretion, and increasing magnesium from 1.2 to 2.4 meq/l resulted in a further depression. Paradoxically, when magnesium was omitted from the perfusing medium, insulin secretion was also depressed. The data strongly suggest that the calcium/magnesium ratio is a primary regulator of the insulin secretory process, since a relatively slight alteration of the physiologic ratio of calcium to magnesium (approximately 2.5) results in a marked alteration of total insulin secretion. In addition, small amounts of magnesium are necessary for optimum secretion, possibly reflecting the requirement for magnesium in several enzymatic processes. Thus, magnesium may play an important role in the regulation of insulin secretion by altering the sensitivity of the beta cells of the Islets of Langerhans to glucose.

Animals↗
PubMed1976

Does somatostatin inhibition of insulin secretion involve two mechanisms of action?

Somatostatin, the hypothalamic growth hormone release inhibitory factor (GHRIF), directly inhibits both the first and second phases of insulin secretion. The sensitivities of these two phases of insulin secretion to somatostatin differ remarkably. The first phase of secretion is approximately 25 to 50 times more sensitive to somatostatin inhibition than is the second phase. In addition, somatostatin inhibition of insulin secretion during the second phase is "reversed" by supplemental calcium, whereas the somatostatin effect on the first phase is unaffected by additional calcium. These findings suggest that the cellular events which produce the two phases of insulin secretion are separate processes, and that somatostatin has a dual mechanism of action in inhibiting insulin secretion.

Animals↗
PubMed1976

Enhancement of insulin secretion by human chorionic somatomammotropin and related hormones.

Hypophysectomized rats were treated for 6 days with 200 mug per day of either human chorionic somatomammotropin, human pituitary growth hormone, plasmin-modified human pituitary growth hormone, or ovine prolactin. All hormone preparations except ovine prolactin enhanced the ability of the pancreases of hypophysectomized rats to secrete insulin in the isolated pancreas perfusion system.

Animals↗
PubMed1975

Dynamics of insulin release by perfused hamster )Mesocricetus auratus) pancreases: effects of hypophysectomy, bovine and human growth hormone, and prolactin.

The hamster exhibits a biphasic pattern of insulin secretion; however, the dynamic response differs qualitatively from that of the rat in that there is a steady-state second release phase. A marked attenuation of insulin secretion as a result of hypophysectomy was observed after 3 weeks, but not after 2 weeks. This depression of insulin secretion was restored to near or above normal levels by bovine growth hormone, human growth hormone, and prolactin.

Animals↗