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D L Curry

Publications and source records attributed to D L Curry.

At least 37 records · Page 2Linked to original sources
PubMed1990

Direct neural effect of lateral hypothalamic stimulation on insulin secretion by pancreases of normal and obese rats.

Perfusion of CNS intact pancreases with 200 mg/dl glucose with concomitant lateral hypothalamic area (LHA) stimulation significantly inhibited insulin secretion both in normal and obese rats. Sprague-Dawley, Zucker lean (FaFa) and Zucker obese (fafa) rats all responded in a similar manner, suggesting a general effect unrelated to metabolic state. Insulin secretion during mins 25-40 of perfusion was inhibited in Sprague Dawley, lean Zucker and obese Zucker rats by 31%, 42% and 33%, even though LHA stimulation took place from mins 20-25. Thus, the duration of inhibition was greater than the period of LHA stimulation, indicating that this pathway can induce prolonged changes in the responsiveness of the pancreas. The data presented in this study demonstrate that LHA stimulation, in the absence of humoral factors, results in a direct CNS-mediated suppression of insulin secretion which is relatively long lasting. This effect may illustrate a basic control mechanism by the CNS to regulate the endocrine pancreas.

Animals↗
PubMed1989

Effects of mannose and fructose on the synthesis and secretion of insulin.

Synthesis-secretion coupling of insulin was determined in perfused pancreases stimulated for 3 h by various sugars. These monosaccharide stimuli included glucose alone at either 200 or 300 mg/dl; mannose or fructose alone at 1,200 mg/dl; or combinations of mannose and fructose or galactose and fructose at 600 mg/dl each. Glucose and mannose each promoted insulin synthesis and secretion. Mannose at 1,200 mg/dl produced synthesis-secretion coupling similar to glucose at 200 mg/dl. Fructose alone at 1,200 mg/dl failed to cause any significant release of insulin, but it did significantly increase beta cell insulin content. When mannose and fructose were combined at 600 mg/dl each, in the absence of glucose, they resulted in a synergistic effect on insulin secretion and an additive effect on insulinogenesis, which was in excess of, or equal to, the insulinotropic effect of glucose at 300 mg/dl. These results clearly establish that the synthesis and secretion of insulin can be uncoupled. Mannose primarily stimulates the putative beta cell glucoreceptor, and fructose signals the insulin biosynthetic pathway. When combined, these monosaccharides couple synthesis-secretion of insulin comparable to glucose. The data suggest that the uncoupling of insulin secretion and synthesis, which may contribute either independently or in combination to abnormalities in pancreatic function observed in various diabetic conditions can be studied using the isolated perfused pancreas model. Use of this relatively physiological experimental model should provide optimal opportunity to further investigate and identify cellular controlling signals regulating either insulin biosynthesis, insulin secretion, or the coupling of both mechanisms.

Animals↗
PubMed1989

Direct effect of CNS on insulin hypersecretion in obese Zucker rats: involvement of vagus nerve.

It is hypothesized that the vagus nerve makes a major contribution to pancreatic insulin hypersecretion in the genetically obese rat (fa/fa) via direct pancreatic innervation. An in situ brain-pancreas perfusion model with intact pancreatic central nervous system (CNS) innervation was used in these studies. The dynamics of insulin secretion in response to a 40-min glucose stimulus (200 mg/dl) was investigated in CNS intact (INT), bilateral cervical vagotomized (VGX), and CNS functionally ablated (ABL) 11- to 12-wk-old homozygous lean (Fa/Fa) and obese (fa/fa) female Zucker rats. The overall pattern of insulin secretory dynamics from obese and lean rats was similar. However, insulin released during the entire 40-min perfusion period by pancreata from obese rats was significantly greater than in lean rats. In lean rats, there was no significant difference in insulin secretion from pancreata of CNS-INT, VGX, and ABL rats. In obese rats, CNS-INT pancreata secreted almost twice as much insulin as pancreata from obese ABL rats and four times as much insulin as CNS-INT lean rats. This demonstrates that hypersecretion of insulin in obese Zucker rats is comprised of a significant direct CNS component. Although vagotomy had little effect on CNS-INT lean rats, it reversed the CNS component of hypersecretion present in CNS-INT obese rats. Because insulin secretion in CNS-INT obese rats was lowered by vagotomy to that equivalent to values of CNS-ABL obese rats, this demonstrates a significant contribution by the parasympathetic nervous system to the hyperinsulinemia seen in the Zucker obese rat that is attributed to direct parasympathetic innervation of the pancreas.

Animals↗
PubMed1989

Synthesis-secretion coupling of insulin. Effect of cyclosporin.

This study investigated the effects of cyclosporin (Cs) on insulin secretion and synthesis from the endocrine pancreas. With in vitro perfused pancreases from control and Cs-treated rats (1, 5, 10, or 25 mg.kg-1.day-1 for 2 wk), a dose-response relationship between Cs dose and inhibition of insulin secretion was demonstrated. Examination of the dynamic secretory response to a glucose stimulus (200 mg/dl) over a 3-h perfusion revealed an inhibition of all three secretory phases. Similarly, the ability of the pancreases to synthesize insulin decreased as a function of Cs dose. Reversibility of Cs toxicity on the pancreas was established by 2 wk after cessation of treatment. To evaluate the effect of Cs treatment in vivo, intravenous glucose tolerance tests were performed. Rats treated with 25 mg.kg-1.day-1 Cs for 2 wk had significantly lower k values (slope of log glucose concentration over time) than controls. At 10 mg.kg-1.day-1, although curves that appeared abnormal were observed, k values were not significantly different from those of controls. In summary, this study demonstrates the profound inhibitory effect of Cs on the endocrine pancreas.

Animals↗
PubMed1988

Pancreatic hypersensitivity to glucose by young obese Zucker rats (fa/fa).

Insulin secretory response to glucose was investigated in 5- to 6-week-old male Zucker obese (fa/fa) and lean (Fa/Fa) rats using a pancreatic perfusion procedure. Blood glucose response to fasting was studied in lean and obese animals over 24 hours. Plasma glucose was slightly elevated in pentobarbital-anesthetized obese rats. However, plasma insulin was 4.6 times greater than that of leans. A hypoglycemic glucose stimulus (75 mg/dL) caused pancreata from obese animals to release 6 times more insulin than lean animals. Stimuli of 125 mg/dL (normoglycemic) and 600 mg/dL (hyperglycemic) caused hypersecretion of 8 and 5 times, respectively. Hypersecretion was not accounted for solely by the twofold increase in pancreatic insulin content. Obese animals had steeper decreases in plasma glucose than lean controls during seven to 13 hours of fasting. Hypersecretion by pancreata from young obese rats to physiological levels of glucose may result in hyperphagia in order to maintain normoglycemia.

Age Factors↗
PubMed1988

Episodic release of insulin by rat pancreas: effects of CNS and state of satiety.

This study reports that insulin is secreted in an episodic manner in rats and that the characteristics of its release can be modified by the central nervous system (CNS) and state of satiety. The pancreata of male Sprague-Dawley rats were perfused using the in situ brain-pancreas technique under urethan anesthesia. Episodic insulin release under non-fasted conditions was not altered by the presence or absence of CNS innervation to the pancreas. Under these conditions the interpeak period was 5.9 and 6 min, respectively, and cycle length was 3.7 and 4 min. However, perfusions that were performed following an overnight fast demonstrated that the CNS is capable of modulating episodic insulin release. After fasting, when comparing CNS-ablated with -intact preparations, the period was shortened from 5.2 to 4.1 min (P less than 0.05), and the number of episodes per 90-min perfusion increased from 16.0 to 19.0 (P less than 0.05) when the pancreas was innervated by the CNS. Additionally, the effect of fasting on denervated pancreata resulted in a shortening of the cycle length, which was prevented when the CNS was functional. These results demonstrate that episodic insulin release can be modified by metabolic conditions and are subject to mediation by the CNS.

Animals↗
PubMed1987

Stimulation of insulin secretion by beta-endorphins (1-27 & 1-31).

Synthetic human beta-endorphin potentiates insulin secretion by the isolated perfused rat pancreas when glucose is present in the perfusate at concentrations of either 125 or 200 mg/dl, whereas it fails to exert any effect on insulin secretion in the presence of a substimulatory concentration of 100 mg/dl. Similar potentiation of insulin secretion occurred in response to the 1-27 fragment (beta-endorphin1-27) of beta-endorphin. This transient potentiation lasts only 3 to 4 minutes, whereupon secretion returns toward control levels. Thus beta-endorphin produces only a transient spike-like secretory profile similar to the first phase of glucose-induced insulin secretion and it fails to produce any chronic insulin secretory response comparable to the second phase of insulin secretion. The insulinotropic effect of beta-endorphins occurred at concentrations varying from 0.1 to 5.0 ug/ml. These data suggest that beta-endorphin and beta-endorphin1-27 potentiate insulin secretion via a common beta cell opioid receptor, and that beta-endorphin may exert a paracrine control of insulin secretion. However, any such regulation appears to be via short-term alterations in the secretory process per se.

Animals↗
PubMed1987

Effect of age on the insulin secretory response of perfused rat pancreas to arginine and tolbutamide.

In this study we compared the ability of perfused pancreases from 2 1/2 month-old and 12 month-old rats to secrete insulin in response to arginine or tolbutamide. The results indicate that the insulin secretory response to either secretagogue was between 25-85% greater (two-way analysis of variance, P less than .01) by perfused pancreases of older rats. On the other hand, islet cell mass was approximately three-fold greater in the pancreases of the older rats. When this difference in mass of insulin secretory tissue was taken into consideration, it became apparent that insulin secretion per beta cell by perfused pancreases of the older rats was only half that of the younger rats in response to either arginine or tolbutamide (two-way analysis of variance, P less than 0.001). Thus, the decline with age in the ability of the beta cell to secrete insulin, previously noted in response to glucose, involves other insulin secretagogues as well.

Aging↗
PubMed1987

Synthesis-secretion coupling of insulin: effect of aging.

Synthesis-secretion coupling of insulin was measured in four age groups of perfused pancreases taken from Sprague-Dawley rats ranging in age from 2-12 months. The effect of long term (6 h) near-maximal glucose stimulation (300 mg/dl) on both insulin secretion and net insulinogenesis demonstrated an age-related increase in both parameters. Net insulinogenesis as well as total insulin secretion increased linearly as a function of aging. Compared to that in 2-month-old rats, total net insulin synthesis was more than 3-fold greater in 12-month-old rats, slightly less than 3-fold greater in 8-month-old rats, and twice as much in 4-month-old rats. Compared to that in 2-month-old rats, total glucose-stimulated insulin secretion was 3-fold greater in 12-month-old rats, approximately 2.2-fold greater in 8-month-old rats, and about 1.7-fold greater in 4-month-old rats. A shorter term (90 min) glucose stimulation at 150 mg/dl produced an age-related increase in insulin secretion which was relatively comparable to the higher glucose stimulus. Of equal importance is that fact that pancreases from the older rats exhibited the same degree of secretory responsiveness to changing glucose levels as did pancreases from the younger rats. Regardless of age, first phase insulin secretion was approximately twice as much in response to the higher glucose level as to the lower. Similarly, second phase insulin secretion was almost 3 times greater regardless of age. When normalized and reported in terms of insulin content, total insulin secretion was no different as a function of aging during the first 1 h of glucose stimulation (i.e. the first two phases of secretion), but it was significantly elevated in the third secretory phase (2-6 h) by the older rat groups. Total 6-h net insulinogenesis was also greater in the older rat groups. When normalized and reported in terms of total body weight, both insulin synthesis and total insulin secretion became comparable and showed no specific age-related difference. Thus, there is no indication that aging results in an uncoupling of relatively long term (6-h) insulin synthesis-secretion, since both glucose-induced responses parallel one another as a function of aging. Furthermore, reporting insulin secretion and synthesis on the basis of body weight, rather than age, totally normalizes synthesis-secretion coupling of insulin.

Aging↗
PubMed1987

Effect of age and sex on rat endocrine pancreas.

Maximal glucose-stimulated insulin secretion was quantified in perfused pancreases of 11-wk-old and 12-mo-old female and male rats. In addition, measurements were made of body weight, total pancreatic weight, and percentage of the pancreas occupied by islet tissue. Body weight (mean +/- SE) of male rats was greater than that of female rats at both 11 wk (319 +/- 3 vs. 237 +/- 13 g) and 12 mo (684 +/- 17 vs. 376 +/- 13 g) of age. Pancreatic weight and percentage of the pancreas occupied by islet tissue were also greater in male rats and increased in approximate proportion to the gain in weight. The first phase and the second phase of maximal glucose-stimulated insulin secretion were both qualitatively and quantitatively similar in all four groups of rats. However, because islet cell mass increased with age, maximal glucose-stimulated insulin secretion declined with age in rats of both sexes when expressed per unit islet tissue. Although the fall in insulin secretion (per islet cell mass) with age was observed in perfused pancreases from both male and female rats, the pancreases of female rats contained relatively less islet tissue and secreted more insulin per unit islet cell mass than pancreases of male rats at either age. Thus, there are sex differences in both islet cell structure and function, but the effect of age on endocrine pancreatic function seems to be independent of sex.

Aging↗
PubMed1986

Insulin content and insulinogenesis by the perfused rat pancreas: effects of long term glucose stimulation.

The dynamic response of the perfused pancreas differed between pancreases from fed and fasted rats. Insulin secretion was significantly lower in pancreases from fasted rats during the first 40 min of perfusion at glucose levels of 200 and 300 mg/dl. Thereafter, from 40-90 min, insulin secretion was similar by pancreases from both fed and fasted rats. The typical biphasic insulin secretory profile, consisting of a transient spike of insulin secretion followed by a slowly rising secretory phase, was observed in pancreases from fasted rats. In contrast, the transition from first to second phase secretion was accelerated in pancreases from fed rats. This suggests that transport of intracellular insulin stores may be accentuated due to the fact that insulinogenic sites (e.g. Golgi) in pancreases from fed rats may be fully primed for optimal secretion. Total pancreatic insulin measurements support this concept. Total pancreatic insulin content was determined under fed and 24-h fasted conditions after various times of perfusion (0, 60, and 90 min and 6 h) and in response to various glucose levels (0, 200, and 300 mg/dl). Fasting resulted in a significant decrease in insulin content at zero time compared with pancreases from fed rats (39.2 +/- 2.4 vs. 61.6 +/- 9.8 micrograms). In the fed rat pancreases, total insulin content decreased slightly after a 60-min glucose stimulus of 300 mg/dl, but returned to the basal level after 90 min and remained at that level during a 6-h period of perfusion. In the fasted state, insulin content remained constant as a function of time until 60 min, but increased by 90 min to a level comparable to that in pancreases from fed rats. The response to lower levels of glucose stimulation (200 mg/dl) was qualitatively similar by pancreases from fed and fasted rats compared to the response to a higher glucose dose (300 mg/dl), except that secretion was less. Insulin content remained relatively constant for periods of perfusion up to 60 min. Insulinogenesis (defined as de novo synthesis and conversion of existing preproinsulin and proinsulin to insulin, less intracellular degradation of insulin) was increased as a function of glucose concentration and differed temporally as a function of the food intake of the animal. At no time of perfusion with any level of glucose stimulation did the insulin content exceed the zero time value in pancreases from fed rats. This suggests that insulin secretion is the rate-limiting step for insulinogenesis.

Animals↗
PubMed1985

Effects of intravenous infusion of doxorubicin on blood chemistry, blood pressure and heart rate in rabbits.

The effects of a 1 h continuous infusion of doxorubicin (12.5 mg kg-1, 200 mg M-2) on blood chemistry was examined in rabbits over a 6-h period. Plasma glucose levels remained unchanged while insulin levels were significantly decreased to 39, 45 and 61% of the zero time value (12.8 +/- 2.9 ng ml-1) at 30, 60 and 120 min, respectively, after starting the drug infusion. Plasma cortisol levels were increased to 141, 140 and 131% of the initial zero time value (12.3 +/- 2.2 ng ml-1) at 120, 240 and 360 min, respectively. Doxorubicin had no effect on plasma electrolytes, osmolality and urea nitrogen but significantly increased plasma creatinine over the corresponding control value (2.2 +/- 0.8 micrograms ml-1 to 4.9 +/- 0.7 micrograms ml-1) at 120 min and the level remained elevated for the remaining period of the study. Systolic and diastolic pressure, and heart rate were also depressed at 240 and 360 min. The data collected in the present study indicate that the doxorubicin infusion might have a direct effect on beta cells in the pancreas as well as muscle tissue. Changes in cortisol, blood pressure and heart rate appear to be secondary to other effects produced by doxorubicin.

Animals↗
PubMed1985

Effects of intratracheal administration of bleomycin or saline in pair-fed and control-fed hamsters on daily food intake and on plasma levels of glucose, cortisol, and insulin, and lung levels of calmodulin, calcium, and collagen.

In the present study, the effects of intratracheal administration of bleomycin have been examined on daily food intake and on plasma levels of glucose, cortisol, and insulin, and on lung levels of calmodulin, calcium, and collagen in hamsters. Since bleomycin treatment caused nutritional deficiency leading to loss of body weight, we have included pair-fed and control-fed as control groups in order to rule out the nutritional deficiency-related effects on these measurements. Bleomycin-treated animals showed a dramatic decrease in daily food intake and body weight as compared to control-fed animals. Bleomycin-treated animals were hyperglycemic when compared to nutritionally comparable pair-fed animals and had plasma glucose levels similar to those of control-fed animals. Plasma cortisol levels in bleomycin-treated and pair-fed animals showed a time-dependent increasing trend, whereas plasma insulin levels in both groups tended to decrease. The lung levels of calmodulin and calcium in bleomycin-treated animals were significantly increased when compared with the pair-fed or control-fed group. Bleomycin-treated animals had significantly higher levels of lung collagen than pair-fed or control-fed at 7 and 13 days after treatment. The lung collagen content in pair-fed animals was significantly less than that of control-fed at 13 days. It was concluded that a disturbance in carbohydrate metabolism and increased lung levels of calmodulin and calcium might be somehow involved in fibroproliferative changes of the lung in bleomycin-treated animals.

Animals↗
PubMed1985

Dynamics of insulin hypersecretion by obese Zucker rats.

The relationship between obesity and hypersecretion of insulin by the pancreas was studied. We found that pancreata from obese Zucker rats secrete significantly more insulin than do pancreata from lean Zucker rats. At a glucose stimulation of 300 mg/dL, the overall dynamic biphasic insulin secretory profiles from obese and lean rats were similar. Further studies to investigate the glucose-insulin dose response relationship in obese and lean rat pancreata demonstrated insulin hypersecretion by pancreata from obese rats which was particularly pronounced at normoglycemic and hypoglycemic levels (by factors as much as 14-fold). This hypersecretion is so striking as to suggest that in the intact state the obese animal may lack the ability to readily "shut off" its insulin secretion under normoglycemic conditions, whereas lean animals possess such an ability. Under hypoglycemic conditions (75 mg/dL), the hypersecretion is transient and insulin secretion returns to normal basal levels after 30 minutes of perfusion. Thus the degree to which this hypersecretory phenomenon may occur in vivo remains to be established.

Animals↗
PubMed1985

Dynamics of pancreatic insulin release in young Zucker rats: a heterozygote effect.

Total pancreatic insulin, dynamic insulin response to glucose (325 mg/dl), or tolbutamide (40 mg/dl) using the isolated perfused pancreas preparation and body composition were determined for 2- and 4-wk-old homozygous lean Fa/Fa, heterozygous lean Fa/fa, unknown lean Fa/??, and homozygous obese fa/fa female Zucker rats. At 2-wk, obese rats (body fat greater than 16%) released significantly more insulin than homozygous lean rats during first (min 10-16) and second phases (min 17-70) (61 vs. 30 ng and 637 vs. 255 ng, respectively). Plasma insulinemia was 177 microU/ml in obese, compared with 51 microU/ml in homozygous lean rats. The dynamic response of unknown lean followed the pattern of either the homozygous lean or the obese rats. There was no significant difference in total pancreatic insulin among any of the groups at 2 wk of age (Fa/Fa, 1.72; Fa/??, 2.01; and Fa/Fa, 1.80 micrograms). At 4 wk, the dynamic response by obese (2.98 micrograms) was similar to that of heterozygous (3.31 micrograms), both being significantly greater than the homozygous lean (1.14 micrograms) or unknown lean rats (1.77 microgram). Total pancreatic insulin in 4-wk obese (19.8 micrograms) was greater than homozygous lean rats (14.5 micrograms). Tolbutamide-stimulated insulin release was significantly greater in 4-wk obese than homozygous lean rats. Exposure to tolbutamide reduced by 60% the second-phase insulin release in both obese and homozygous lean rats during a subsequent 40-min glucose (325 mg/dl) perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗