Synchronization of ovulation and fertility in weaned sows treated with intravaginal triptorelin is influenced by timing of administration and follicle size.

A 100 µg dose of triptorelin was tested for synchronizing ovulation in sows. In Experiment 1, conducted in April through June, sows (n = 125) were assigned to Control (untreated), TG-96 (Triptorelin Gel (TG) given intravaginally at 96 h post-weaning), or TG-E (given intravaginally at estrus). To optimize AI timing, sows were inseminated at 2 and 26 h after estrus for Control and TG-E and at 8 and 32 h following TG-96. Ovulation by 48 h post-treatment tended to be affected by treatment (P = 0.08) and more (P < 0.05) TG-96 sows ovulated (57.9%) compared to Controls (34.2%), but TG-E (45.1%) did not differ (P > 0.10). Duration of estrus was reduced (P < 0.005) in TG-96 (51 h) and TG-E (58 h) compared to Controls (65 h). There was no treatment effect on farrowing rate (71%) or total born (10.4). Average follicle size <6.5 mm at 96 h after weaning was associated with reduced (P < 0.01) estrus, ovulation and farrowing rate. Experiment 2 was conducted in August through September using 503 weaned sows. The TG-96 treatment reduced duration of estrus (P = 0.03), but treatment did not affect estrus expression, farrowing rate or total pigs born. In conclusion, use of a 100 µg dose of triptorelin intravaginally at 96 h or at estrus advanced ovulation and when used with timed insemination, resulted in similar farrowing rates and litter sizes comparable to sows mated based on estrus. However, ovulation induction and timed AI success may benefit from an approach that ensures sows have adequate follicle development at time of treatment.

Endocrine, ovulatory and reproductive characteristics of sows treated with an intravaginal GnRH agonist.

The present study examined the effectiveness of intravaginal administration of a GnRH agonist, triptorelin, on the induction of the preovulatory LH surge; synchronization of time of ovulation; and reproductive characteristics in weaned sows. Sows were given 100microg of triptorelin in 0.9, 1.2, or 1.5% methylcellulose gel intravaginally 96h after weaning and then bred at 8 and 32h post-treatment. Untreated sows inseminated once each day of estrus served as the positive controls, while females treated with only the methyl cellulose gel and also bred once each day of estrus were negative controls. Sows treated intravaginally with triptorelin exhibited preovulatory LH surges with magnitudes comparable to those that occurred spontaneously in the negative controls. Preovulatory LH surges were initiated over a narrow and well-defined time interval that occurred 4-12h after treatment in sows receiving triptorelin in 1.2 or 1.5% methyl cellulose gel. As a result, the majority of the sows in these two treatments had ovulations within a 12h time frame 36-48h after treatment. In contrast, both the LH surge and ovulation occurred over extended periods of time after weaning in negative controls and sows given triptorelin in 0.9% methylcellulose gel. Farrowing rates and litter size were similar between untreated controls and triptorelin-treated sows that were bred with two fixed timed inseminations. Insemination of sows induced to have ovulations and bred at least once while not in estrus did not have any overt negative effects on reproductive characteristics. These results demonstrate that 100microg of triptorelin administered intravaginally in a least 1.2% methyl cellulose gel induced a normal preovulatory LH surge and synchronized time of ovulation in weaned sows. Furthermore, there were no obvious changes in reproductive performance when these sows were bred with two fixed time inseminations regardless of whether they exhibited a standing reflex.

Efficacy of an intravaginal progesterone insert and an injection of PGF2alpha for synchronizing estrus and shortening the interval to pregnancy in postpartum beef cows, peripubertal beef heifers, and dairy heifers.

The objective was to test the efficacy of an intravaginal progesterone insert and injection of PGF2alpha for synchronizing estrus and shortening the interval to pregnancy in cattle. Cattle were assigned to one of three treatments before a 31-d breeding period that employed artificial insemination. Control cattle were not treated, and treated cattle were administered PGF2alpha or an intravaginal progesterone-releasing insert (CIDR) for 7 d and treated with PGF2alpha on d 6. The treatments were applied in one of three experiments that involved postpartum beef cows (Exp. 1; n = 851; 56+/-0.6 d postpartum), beef heifers (Exp. 2; n = 724; 442.5+/-2.8 d of age), and dairy heifers (Exp. 3; n = 260; 443.2+/-4.5 d of age). Luteal activity before treatment was determined for individual cattle based on blood progesterone concentrations. In Exp. 1, there was a greater incidence of estrus during the first 3 d of the breeding period in CIDR+PGF2alpha-treated cows compared with PGF2alpha-treated or control cows (15, 33, and 59% for control, PGF2alpha, and CIDR+PGF2alpha, respectively; P < 0.001). The improved estrous response led to an increase in pregnancy rate during the 3-d period (7, 22, and 36% for control, PGF2alpha, and CIDR+PGF2alpha, respectively; P < 0.001) and tended to improve pregnancy rate for the 31-d breeding period for cows treated with CIDR+PGF2alpha, (50, 55, and 58% for control, PGF2alpha, and CIDR+PGF2alpha, respectively, P = 0.10). Improvements in rates of estrus and pregnancy after CIDR+PGF2alpha, were also observed in beef heifers. Presence of luteal activity before the treatment period affected synchronization and pregnancy rates because anestrous cows (Exp. 1) or prepubertal heifers (Exp. 2) had lesser synchronization rates and pregnancy rates during the first 3 d of the breeding period as well as during the entire 31-d breeding period. The PGF2alpha, and CIDR+PGF2alpha but not the control treatments were evaluated in dairy heifers (Exp. 3). The CIDR+PGF2alpha-treated heifers had a greater incidence of estrus (84%) during the first 3 d of the breeding period compared with the PGF2alpha-treated heifers (57%), but pregnancy rates during the first 3 d or during the 31-d breeding period were not improved for CIDR+PGF2alpha compared with PGF2alpha-treated heifers. In summary, the concurrent treatment of CIDR and PGF2alpha improved synchronization rates relative to PGF2alpha alone or control. Improved estrus synchrony led to greater pregnancy rates for beef cows and beef heifers but failed to improve pregnancy rates for dairy heifers.

Induced and synchronized estrus in cattle: dose titration of estradiol benzoate in peripubertal heifers and postpartum cows after treatment with an intravaginal progesterone-releasing insert and prostaglandin F2alpha.

Peripubertal beef heifers (n = 57) and postpartum multiparous cows (n = 52) were used to determine the optimal dose of estradiol benzoate (EB) to induce and synchronize estrus after treatment with intravaginal progesterone inserts (IVP4, EAZI-BREED CIDR). All females received an IVP4 for 7 d (d 0 = insertion day) with a 25-mg injection of PGF2alpha (Lutalyse) on d 6. At 24 to 30 h after IVP4 removal, females were randomly assigned to be injected subcutaneously with EB at the following doses: heifers 0, .2, .38, or .75 mg and cows 0, .25, .5, or 1 mg. Furthermore, seven heifers and seven cows from each dose group were bled every 4 h for 76 h starting at EB injection. Serum was collected and assayed for LH and estradiol-17beta (E2). Observations for signs of estrus were made twice daily for 21 d after removal of IVP4, and females were artificially inseminated 8 to 20 h after detection of estrus. The percentage of females showing estrous behavior was increased by EB (P < .04); the greatest response was at .38 mg in heifers (86%) and 1 mg in cows (100%). Dose x time interaction affected (P < .01) E2 concentrations in heifers and cows; the animals that received the higher doses of EB had greater E2 concentrations in a shorter time than those that received the smaller doses. The percentage of cows and heifers with an acute preovulatory LH release (peak LH) was affected by dose, with a linear (P < .01) and a quadratic (P < .01) response. Highest concentrations of LH during peak LH were affected by dose with a linear (P < .01) response in heifers and linear (P < .01) and quadratic (P < .08) responses in cows. Heifers receiving .38 mg and cows receiving .5 and 1 mg of EB had the highest peak LH. Time to LH peak had a linear (P < .03) response in heifers and had linear (P < .04) and quadratic (P < .05) responses in cows. Pregnancy rate was affected (P < .02) in heifers by whether or not they were anestrous before IVP4 treatment (those with estrous cycles = 52% vs those that were anestrous = 22%) and in cows by dose of EB (P < .01; 8, 23, 21, and 67% for 0, .25, .5, and 1 mg, respectively). In conclusion, in females treated with IVP4 and PGF2alpha to induce and synchronize estrus, an injection of EB increased concentrations of E2 and LH and increased number of animals showing estrus. Also, EB increased pregnancy rates in cows. Optimal responses were at .38 mg EB for heifers and at 1 mg EB for cows.

Chronic recombinant equine somatotropin (eST) administration does not affect aerobic capacity or exercise performance in geriatric mares.

The purpose of this experiment was to test the hypothesis that chronic (89 days) administration of recombinant equine somatotropin (eST) would increase aerobic capacity and improve exercise performance in old mares. Fifteen, healthy, unfit, aged (20-26 year old) mares were randomly assigned to a treatment (eST, 12.5 mg day-1 in 3 ml glycine/manitol buffer, s.c., n = 7) or control (vehicle, 3 ml day-1, s.c., n = 8) group. Aerobic capacity and exercise performance were measured using a standardized exercise test (SET) performed on a high speed treadmill. Tests were conducted before (-21 days), during (+43 days and +89 days) and after (+127 days) treatment. During the SET, resting data were collected and the horses then ran up a fixed 6% grade, starting at 4 m s-1, with a 1 m s-1 increase every 60 s (omitting 5 m s-1) until fatigue. Oxygen uptake (VO2) was measured using an open flow calorimeter and blood lactate concentration (LA) via a lactate analyser. Venous blood samples (10 ml) were collected at rest, during the last 10 s of each step of the SET, and after exercise and used to measure LA, plasma protein concentration (PP), hematocrit (HCT), and the plasma concentrations of creatine kinase (CK) and aspartamine transferase (AST). There were no differences (P > 0.05) in resting VO2, LA, TPP, or HCT due to treatment or test time. Furthermore, there were no differences (P > 0.05) in maximal oxygen uptake (VO2max), top run velocity, run time, watts at VO2max, velocity to produce a lactate of 4 mmoll-1 (VLA4), watts at VLA4, peak HCT or peak LA. Finally, there were no differences (P > 0.05) in resting or post-exercise CK or AST. These data indicate that chronic eST administration does not affect aerobic capacity or indices of exercise performance in unfit aged mares.

Luteal function and estrus in peripubertal beef heifers treated with an intravaginal progesterone releasing device with or without a subsequent injection of estradiol.

The objectives of this experiment were to determine if treatment of beef heifers with progesterone (P4) using an intravaginal device alone or in combination with estradiol benzoate (EB) would induce estrus and cause development of corpora lutea (CL) with a typical life span. Peripubertal heifers (n = 311) were used when about 40% of the heifers had a functional CL. The heifers were assigned to receive one of the following treatments on Day 0: 1) a sham device for 7 d (C, n = 108); 2) an intravaginal device containing P4 for 7 d (P, n = 102); or 3) an intravaginal device containing P4 for 7 d plus an injection of 1 mg EB 24 to 30 h after device removal (PE, n = 101). Serum concentrations of P4 were determined on Days -7, 0, 8, 15 and 22. Weight and age of the heifers at the start of the trial averaged 292 +/- 45 kg and 365 +/- 38 d, respectively. A greater (P < 0.0001) proportion of the heifers from the PE than P group was in standing estrus (81 vs 37%) and formed normal CL (68 vs 44%) after device removal. Of the heifers exhibiting estrus, a greater (P < 0.05) proportion of PE (94%) than P (80%) heifers was active 1 to 3 d after implant removal. Short-term progesterone treatment increased the proportion of heifers in estrus and those forming normal CL, and adding EB to the progesterone treatment further enhanced these responses.

Pulsatile release of somatotropin related to meal feeding and somatotropin response to secretagogues in horses.

Our goal was to establish a time of day and(or) interval from feeding that would avoid the refractory period after a somatotropin (ST) surge and optimize the responsiveness of horses to ST secretagogues. Two experiments were conducted with eight geldings conditioned to consume grain at 0800 and 1600 daily. In Exp. 1, during a 24-h period, these geldings averaged 3.2 +/- .3 pulses of ST with peak amplitude of 4.2 +/- .4 ng/mL, pulse duration of 55 +/- 6 min, and interpeak interval of 400 +/- 57 min. No ST peaks occurred within 2 h after either grain feeding. In Exp. 2, eight geldings were given 50 micrograms of ST-releasing factor (STRF) at 0800. Two geldings that had a pulse of ST between 0700 and 0800 failed to respond to STRF, but the other six responded with a pulse of ST at 37 +/- 3 min; peak amplitude was 4.6 +/- 2.2 ng/mL and duration was 123 +/- 25 min. Experiments 3 and 4 were with mares aged 20 to 26 yr and conditioned to be fed grain at 0800 daily. In Exp. 3, blood was sampled for 8 h beginning at 0500. Seven of the eight mares had a ST pulse in progress at 0500. Five additional pulses were detected, all from 0740 to 0940, but none from 0600 to 0700 or from 1000 to 1300. In Exp. 4, four of the same eight mares were given 50 micrograms of STRF at 0700 and the other four at 1300. Three of the four treated at 0700 and all four treated at 1300 responded to STRF with ST peaks at 20 +/- 5 min; peak amplitude was 12.7 +/- 9.5 ng/mL and duration was 69 +/- 6 min. In Exp. 5, nine mares aged 20 to 26 yr were fed grain at 0800 and 1600 as in Exp. 1 and 2 and given a nonpeptidal ST secretagogue (STS, Merck L-163,255) i.v. at 0, 1, or 5 mg/kg (n = 3 mares/dose) at 1300. No mare had a pulse of ST during the 1 h before treatment. All six mares given STS responded with ST pulses. The ST responses to STS at 1 and 5 mg/kg did not differ (P > .05); time to ST peak was 35 +/- 4 min, pulse amplitude was 24.0 +/- 6.3 ng/mL, and pulse duration was 100 +/- 9 min. We conclude that mares and geldings fed grain once or twice daily usually have a period of 2 to 5 h after feeding with no ST pulses. When horses are fed grain at 0800, one may give a ST secretagogue at 1300 to avoid a refractory period and improve the probability of an ST response.

Estrus and luteal function in suckled beef cows that were anestrous when treated with an intravaginal device containing progesterone with or without a subsequent injection of estradiol benzoate.

The objectives in this study were to determine whether treatment with progesterone (P4) via an intravaginal device would induce estrus and development of corpora lutea (CL) with typical life spans and whether treatment with estradiol benzoate (EB) following device removal would enhance the responses. At treatment initiation (d 0), suckled beef cows (n = 362) that were anestrous received one of the following: 1) an intravaginal device containing P4 for 7 d plus an injection of 1 mg of EB 24 to 30 h after device removal (P4+EB), 2) an intravaginal device containing P4 for 7 d (P4), 3) a sham device for 7 d plus an injection of 1 mg of EB 24 to 30 h after device removal (EB), or 4) a sham device for 7 d (control). Progesterone treatment increased the proportion of cows that formed CL with a typical lifespan (P < .001) and exhibited behavioral estrus (P < .05). Treatment with EB in combination with P4 increased (P < .001) the proportion of cows that exhibited estrus. Treatment with P4 alone had no effect, but the combination of P4 and EB increased (P < .01) the proportion of cows that formed short-lived or typical lifespan CL by the end of the experiment compared with untreated cows. In summary, treatment with P4 increased the incidence of estrus and the proportion of cows that formed CL with a typical lifespan. Treatment with P4 resulted in resumption of luteal function in suckled beef cows that were anestrous, with most cows developing CL with a typical lifespan, whereas EB enhanced the expression of estrus.

Acute effects of short-term feed deprivation and refeeding on circulating concentrations of metabolites, insulin-like growth factor I, insulin-like growth factor binding proteins, somatotropin, and thyroid hormones in adult geldings.

Two studies were performed with Standardbred geldings 7 to 21 yr of age to determine the sequence of changes in blood plasma concentrations of some hormones and metabolites during feed deprivation for 48 h and for 12 h after refeeding. Plasma hormone and metabolite concentrations were determined with methods validated for horse plasma. Insulin-like growth factor binding proteins (IGFBP) were determined with radioligand analysis following SDS-PAGE electrophoresis. In both experiments, plasma concentrations of triiodothyronine and thyroxine decreased (P < .01) during feed deprivation and increased (P < .01) during refeeding. Plasma glucose and IGF-I either decreased or were not altered during feed deprivation. In contrast, plasma concentrations of NEFA and urea nitrogen increased (P < .01) during feed deprivation and decreased (P < .01) during the refeeding period. Plasma somatotropin (ST) increased (P < .01) approximately 80% at 24 to 36 h of feed deprivation, declined (P < .01) to control values at 48 h of feed deprivation, increased (P < .01) nearly three fold at 3 h after refeeding, and returned to control values by 6 h after refeeding. We identified five IGFBP, and their plasma concentrations were not significantly altered during feed deprivation or following refeeding. We conclude that metabolite availability during feed deprivation and following refeeding alters the secretion of thyroid hormones, ST, and possibly IGF-I, thereby maintaining homeostasis in horses.

Feed intake, body weight, body condition score, musculation, and immunocompetence in aged mares given equine somatotropin.

Sixteen 20- to 26-yr-old mares were given 0, 6.25, or 12.5 mg/d equine somatotropin (eST) to determine whether aged mares respond to ST with changes in feed intake, body weight, body condition score (based mostly on fat cover), or immunocompetence. Neither dry matter intake, body weight, nor body condition scores were altered during the 6 wk of eST injection. However, based on photographs taken to evaluate musculation before and after treatment (scores 0 to 4), mares given eST developed greater (P < .07) muscle definition (1.8 +/- .6 and 2.5 +/- .6 for 6.25 and 12.5 mg eST/d, respectively) than control mares (.7 +/- .4). Total circulating leukocytes increased (P < .05) in both of the eST-treated groups during the 6-wk injection period, caused by an increase (P < .05) in granulocytes. Lymphocyte numbers were not altered. Granulocyte oxidative burst activity was not altered by eST treatment. Although lymphocyte proliferative responses to phytohemagglutinin, pokeweed mitogen, or lipopolysaccharide were not altered during the treatment period, lymphocyte proliferation in response to phytohemagglutinin and pokeweed mitogen increased twofold in eST-treated horses at 2 wk after eST treatment. In overview, the increased musculation and the increase in granulocyte numbers in mares given eST suggest that eST supplementation may improve the health and well-being of aged mares.

Age and breed differences in thyroid hormones, insulin-like growth factor (IGF)-I and IGF binding proteins in female horses.

A survey with horses was conducted to determine whether plasma concentrations of triiodothyronine (T3), thyroxine (T4), insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP) change as horses grow, mature sexually, and age. Jugular blood was sampled from Standardbred fillies and mares at ages 0, 1, 7, and 14 d, at 1, 2, 4, 5, 6, and 9 mo, and at 5 to 8 and 16 to 22 yr (n = 5 to 18). In a second survey, we measured the same variables in eight breeds of horses with markedly different adult body sizes, from Miniatures to Friesians. Plasma T3, T4, and IGF-I were determined by radioimmunoassays validated for horses, and IGFBP were estimated from radioligand assay following separation of the IGFBP by SDS-PAGE electrophoresis. Plasma T3 decreased (P < .01) nearly continuously from 7.9 ng/mL on the day of birth to .9 ng/mL at 6 mo, and then changed little from .7 ng/mL at 9 mo to .5 ng/mL in mares 16 to 22 yr old. Similarly, T4 declined (P < .01) from 233 ng/mL on the day of birth to 49 ng/mL at 14 d and varied from 35 to 9 ng/mL among all of the older age groups. Plasma concentrations of IGF-I increased (P < .01) from 285 ng/mL on the day of birth to 572 ng/mL at 14 d, remained relatively constant until 9 mo of age (530 ng/mL), and then declined (P < .01) to low levels (295 ng/mL) in the oldest mares. We detected six IGFBP. The two smallest IGFBP (26 and 39 kDa) were highest during the first 14 d after birth and lowest (P < .01) in aged mares. The four larger IGFBP were lowest at birth and increased to the highest values during the most rapid growth period, but these changes were not significant (P > .20). In agreement with data for other species, our data suggest that IGF-I and IGFBP modulate growth in horses. Although there were impressive interbreed differences in circulating concentrations of T3, T4, IGF-I, and IGFBP, these were not related to differences in adult body size.

The hypothalamo-pituitary gonadotrophic axis of suckled and nonsuckled dairy cows postpartum.

The objective was to determine whether the suckling-induced delay in return to estrus postpartum could be explained by changes in hypothalamic LHRH content or ability of the pituitary to release LH and FSH in response to LHRH or 59 mM K+ in vitro. In addition, serum concentrations of several other hormones were measured. Nine Holstein cows were suckled ad libitum by two calves and milked by machine twice daily and eight were milked by machine only from calving until slaughter on day 14 postpartum. On day 13 postpartum, blood was collected at 15-min intervals from 0815 to 1200 hr and from 2015 to 2400 hours. Suckled cows had lower (P less than .05) mean serum LH concentrations on day 13 postpartum than did nonsuckled controls. This decrease resulted from a 60% reduction in frequency and a 40% reduction in amplitude of episodic LH peaks. Suckling did not affect body weight change postpartum or serum concentrations of progesterone, estradiol-17 beta, total glucocorticoids, prolactin or FSH during the first 14 days postpartum. The suckling-induced decrease in serum LH was not reflected by a reduction in hypothalamic LHRH or pituitary LH on day 14 postpartum. However, pituitary explants from suckled cows on day 14 postpartum secreted 50% less (P less than .01) LH in response to LHRH (25 ng/ml for 30 min) or K+ (59 mM for 30 min) in vitro than did those from nonsuckled cows. Secretion of FSH was increased 20-fold by LHRH and K+ in vitro, but differences due to suckling treatment were not significant. Decreased frequency and amplitude of episodic LH secretion in vivo and reduced capacity of pituitaries to respond to LHRH may be the cause of suckling-induced inhibition of postpartum ovulation in cattle.

Suckling and four-times daily milking: influence on ovulation, estrus and serum luteinizing hormone, glucocorticoids and prolactin in postpartum holsteins.

Holstein cows were assigned at calving to be (1) milked at 12-hr (n = 5) or (2) 6-hr (n =5) intervals or (3) suckled ad libitum by one calf and milked at 12-hr intervals (n = 6). Suckling resulted in an increase in the postpartum (PP) interval to first ovulation (39.7 vs 21.2 days), but increased milking frequency did not. Delayed resumption of episodic luteinizing hormone (LH) secretion was associated with the increased PP interval to ovulation in suckled cows. Both frequency and amplitude of episodic LH peaks were reduced (P less than .05) on days 7 and 14 PP in suckled cows compared to nonsuckled cows (1.2 vs 2.5 peaks/4.5 hr and 1.8 vs 2.8 ng/ml, respectively). Suckling did not significantly modify basal of milking-induced concentrations of prolactin or total glucocorticoids. Nor did serum concentrations of progesterone or estradiol-17 beta differ between suckled and nonsuckled cows, or between day 7 and day 14 PP. Milking-induced secretion of both prolactin and total glucocorticoids were greater (P less than .05) on day 14 PP than on day 7 PP in both suckled and nonsuckled cows. These results suggest that suckling may delay the first PP ovulation by suppressing episodic LH secretion. Alternations in prolactin, total glucocorticoids, progesterone or estradiol-17 beta do not apper to mediate directly the effects of suckling on PP episodic LH secretion and (or) ovulation.

Serum glucocorticoids, growth hormone and insulin and plasma glucose in bulls given prostaglandin E2 or F2 alpha 1.

Plasma glucose and serum insulin, growth hormone and glucocorticoid concentrations were determined in five yearling bulls given (im) 5, 15 or 30 mg prostaglandin E2 (PGE2), 30 mg prostaglandin F2 alpha(PGF2 alpha) or saline. Jugular blood was collected at frequent intervals around the time of injection and at .5--hr intervals from 1 to 9 hr after injections. Thirty milligrams PGE2 and 30 mg PGF2 alpha each caused 15- to 20-fold increases in serum glucocorticoids. Glucocorticoids increased with increasing doses of PGE2. Although PGE2 and PGF2 alpha each increased blood growth hormone, this effect was about twofold larger after PGE2. By contrast, PGE2 depressed serum insulin about 50% for 1 hr, then insulin increased about sixfold until 3 to 4 hours. Blood serum insulin increased after PGF2 alpha, but this effect only approached significance (P less than .10). Plasma glucose increased about 10 mg/100 ml after PGE2, but was not affected significantly by PGF2 alpha. Thus, the effects of PGE2 and PGF2 alpha on hormones which control glucose metabolism differ markedly. We speculate that PGE2 caused a twofold increase in growth hormone secretion within 10 to 20 min, that increased growth hormone induced increased blood glucose within 1 to 2 hr and that increased glucose caused increased insulin secretion at 2 to 4 hr, but we cannot rule out a transitory (1 hr) suppressive effect of PGE2 directly on the pancreas.