human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene . We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene . METHODS We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome . Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo .  Serum progesterone was measured on days 14 , 28 , 35 , 44 , and 53 , and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter ( 26 nmol per liter ) on any of these days . RESULTS Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study . Among the 21 women given metformin plus clomiphene , the mean ( + /-SE ) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute ( 40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute , P=0.03 ) , but it did not change significantly in the 25 women given placebo plus clomiphene . Nineteen of the 21 women ( 90 percent ) who received metformin plus clomiphene  ovulated ( mean peak serum progesterone concentration , 23.8+/-3.4 ng per milliliter [ 7.6+/-10.9 nmol per liter ] ) . Two of the 25 women ( 8 percent ) who received placebo plus clomiphene  ovulated ( P<0.001 ) . Overall , 31 of the 35 women ( 89 percent ) treated with metformin  ovulated spontaneously or in response to clomiphene  , as compared with 3 of the 26 women ( 12 percent ) treated with placebo . CONCLUSIONS The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin OBJECTIVE To determine whether the administration of D-chiro-inositol , a putative insulin-sensitizing drug , would affect the concentration of circulating insulin , the levels of serum and rogens , and the frequency of ovulation in lean women with the polycystic ovary syndrome . METHODS In 20 lean women ( body mass index , 20.0 to 24.4 kg/m 2 ) who had the polycystic ovary syndrome , treatment was initiated with either 600 mg of D-chiro-inositol or placebo orally once daily for 6 to 8 weeks . We performed oral glucose tolerance tests and measured serum sex steroids before and after therapy . To monitor for ovulation , we determined serum progesterone concentrations weekly . RESULTS In the 10 women given D-chiro-inositol , the mean ( + /- st and ard error ) area under the plasma insulin curve after oral administration of glucose decreased significantly from 8,343 + /- 1,149 mU/mL per min to 5,335 + /- 1,792 mU/mL per min in comparison with no significant change in the placebo group ( P = 0.03 for difference between groups ) . Concomitantly , the serum free testosterone concentration decreased by 73 % from 0.83 + /- 0.11 ng/dL to 0.22 + /- 0.03 ng/dL , a significant change in comparison with essentially no change in the placebo group ( P = 0.01 ) . Six of the 10 women ( 60 % ) in the D-chiro-inositol group ovulated in comparison with 2 of the 10 women ( 20 % ) in the placebo group ( P = 0.17 ) . Systolic ( P = 0.002 ) and diastolic ( P = 0.001 ) blood pressures , as well as plasma triglyceride concentrations ( P = 0.001 ) , decreased significantly in the D-chiro-inositol group in comparison with the placebo group , in which these variables either increased ( blood pressure ) or decreased minimally ( triglycerides ) . CONCLUSION We conclude that , in lean women with the polycystic ovary syndrome , D-chiro-inositol reduces circulating insulin , decreases serum and rogens , and ameliorates some of the metabolic abnormalities ( increased blood pressure and hypertriglyceridemia ) of syndrome Some actions of insulin are mediated by inositolphosphoglycan ( IPG ) mediators . Deficient release of a putative D-chiro-inositol-containing ( DCI ) IPG mediator may contribute to insulin resistance in women with polycystic ovary syndrome ( PCOS ) . Previously , we demonstrated that oral DCI supplementation improved ovulation and metabolic parameters in women with PCOS . However , whether oral DCI mediates an increase in the release of the DCI-IPG mediator and an improvement in insulin sensitivity in women with PCOS is unknown . We conducted a r and omized controlled trial of DCI supplementation vs placebo in 11 women with PCOS who were assessed at 2 time points 6 weeks apart .  Plasma DCI , DCI-IPG release during oral glucose tolerance test ( AUC(DCI-IPG ) ) , and insulin sensitivity ( S(i ) ) by frequently sample d intravenous glucose tolerance test were assessed at baseline and end of study . The study was terminated early because of a sudden unavailability of the study drug . However , in all subjects without regard to treatment assignment , there was a positive correlation between the change in AUC(DCI-IPG)/AUC(insulin ) ratio and the change in S(i ) during the 6-week period ( r = 0.69 , P = .02 ) , which remained significant after adjustment for body mass index ( P = .022 ) and after further adjustment for body mass index and treatment allocation ( P = .0261 ) . This suggests that , in women with PCOS , increased glucose-stimulated DCI-IPG release is significantly correlated with improved insulin sensitivity . The significant relationship between DCI-IPG release and insulin sensitivity suggests that the DCI-IPG mediator may be a target for therapeutic interventions in PCOS Some actions of insulin are mediated by putative inositolphosphoglycan mediators , and a deficiency in D-chiro-inositol-containing inositolphosphoglycan ( DCI-IPG ) may contribute to insulin resistance in women with polycystic ovary syndrome ( PCOS ) . Furthermore , similar effects of DCI and metformin , an insulin-sensitizing drug , have been demonstrated in PCOS women . To determine whether metformin improves insulin actions by increasing biologically active DCI-IPG in women with PCOS , we analyzed DCI-IPG during an oral glucose tolerance test in 19 obese women with PCOS before and after 4 - 8 wk of metformin or placebo .  After treatment , the mean ( + /-SE ) area under the curve ( AUC ) during the oral glucose tolerance test of insulin ( AUC(insulin ) ) decreased significantly more in the metformin group , compared with the placebo group [ -3574 + /- 962 vs. + 1367 + /- 1021 micro IU/min.ml ( -26 + /- 7 vs. + 10 + /- 7 nmol/min.liter ) , P = 0.003 ] , but the AUC of DCI-IPG ( AUC(DCI-IPG ) ) decreased similarly in both groups ( -1452 + /- 968 vs. -2207 + /- 1021%/min , P = 0.60 ) . However , the ratio of AUC(DCI-IPG)/AUC(insulin ) increased by 160 % after metformin and decreased by 29 % after placebo ( P = 0.002 between groups ) . Moreover , metformin seemed to improve the positive correlation between AUC(DCI-IPG ) and AUC(insulin ) but not placebo ( r = 0.32 , P = 0.68 at baseline ; r = 0.52 , P = 0.12 after metformin ; and r = -0.39 , P = 0.30 after placebo ) . We conclude that in obese women with PCOS , metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators , as evidence d by increased bioactive DCI-IPG released per unit of insulin BACKGROUND Obese women with polycystic ovary syndrome ( PCOS ) manifest impaired insulin-stimulated release of a d-chiro-inositol-containing inositolphosphoglycan ( DCI-IPG ) insulin mediator during oral glucose tolerance testing ( OGTT ) , which appears to be restored by the administration of metformin . This suggests that either obesity or PCOS is associated with a defect in the coupling of the stimulation of the insulin receptor by insulin to the release of the DCI-IPG mediator . The objective of this study was to compare the release of bioactive DCI-IPG between normal nonobese women and obese PCOS women during stimulation with two different concentrations of insulin when glucose levels are clamped . METHODS We performed a cross-sectional case-control study at the clinical research center of an academic medical center . A two-step euglycemic-hyperinsulinemic clamp was carried out in 8 nonobese normal and 8 obese PCOS women , during which DCI-IPG bioactivity was monitored . RESULTS At baseline , PCOS women were significantly more obese , hyperinsulinemic , and insulin resistant than the controls . During the clamp studies , DCI-IPG bioactivity increased significantly over the first 45 min of the low-insulin step of the clamp in normal nonobese women ( P = 0.046 ) and then decreased to baseline levels ; DCI-IPG increased again after initiation of the high-insulin step ( P = 0.029 ) . Despite higher insulin levels during the clamp in PCOS women , DCI-IPG bioactivity remained flat throughout both insulin steps and was thus significantly lower than in controls during the initial periods of both steps . CONCLUSIONS The coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in obese PCOS women , which may contribute to the insulin resistance in these women 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene . We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene . METHODS We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome . Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo .  Serum progesterone was measured on days 14 , 28 , 35 , 44 , and 53 , and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter ( 26 nmol per liter ) on any of these days . RESULTS Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study . Among the 21 women given metformin plus clomiphene , the mean ( + /-SE ) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute ( 40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute , P=0.03 ) , but it did not change significantly in the 25 women given placebo plus clomiphene . Nineteen of the 21 women ( 90 percent ) who received metformin plus clomiphene  ovulated ( mean peak serum progesterone concentration , 23.8+/-3.4 ng per milliliter [ 7.6+/-10.9 nmol per liter ] ) . Two of the 25 women ( 8 percent ) who received placebo plus clomiphene  ovulated ( P<0.001 ) . Overall , 31 of the 35 women ( 89 percent ) treated with metformin  ovulated spontaneously or in response to clomiphene  , as compared with 3 of the 26 women ( 12 percent ) treated with placebo . CONCLUSIONS The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin OBJECTIVE To determine whether the administration of D-chiro-inositol , a putative insulin-sensitizing drug , would affect the concentration of circulating insulin , the levels of serum and rogens , and the frequency of ovulation in lean women with the polycystic ovary syndrome . METHODS In 20 lean women ( body mass index , 20.0 to 24.4 kg/m 2 ) who had the polycystic ovary syndrome , treatment was initiated with either 600 mg of D-chiro-inositol or placebo orally once daily for 6 to 8 weeks . We performed oral glucose tolerance tests and measured serum sex steroids before and after therapy . To monitor for ovulation , we determined serum progesterone concentrations weekly . RESULTS In the 10 women given D-chiro-inositol , the mean ( + /- st and ard error ) area under the plasma insulin curve after oral administration of glucose decreased significantly from 8,343 + /- 1,149 mU/mL per min to 5,335 + /- 1,792 mU/mL per min in comparison with no significant change in the placebo group ( P = 0.03 for difference between groups ) . Concomitantly , the serum free testosterone concentration decreased by 73 % from 0.83 + /- 0.11 ng/dL to 0.22 + /- 0.03 ng/dL , a significant change in comparison with essentially no change in the placebo group ( P = 0.01 ) . Six of the 10 women ( 60 % ) in the D-chiro-inositol group ovulated in comparison with 2 of the 10 women ( 20 % ) in the placebo group ( P = 0.17 ) . Systolic ( P = 0.002 ) and diastolic ( P = 0.001 ) blood pressures , as well as plasma triglyceride concentrations ( P = 0.001 ) , decreased significantly in the D-chiro-inositol group in comparison with the placebo group , in which these variables either increased ( blood pressure ) or decreased minimally ( triglycerides ) . CONCLUSION We conclude that , in lean women with the polycystic ovary syndrome , D-chiro-inositol reduces circulating insulin , decreases serum and rogens , and ameliorates some of the metabolic abnormalities ( increased blood pressure and hypertriglyceridemia ) of syndrome Some actions of insulin are mediated by inositolphosphoglycan ( IPG ) mediators . Deficient release of a putative D-chiro-inositol-containing ( DCI ) IPG mediator may contribute to insulin resistance in women with polycystic ovary syndrome ( PCOS ) . Previously , we demonstrated that oral DCI supplementation improved ovulation and metabolic parameters in women with PCOS . However , whether oral DCI mediates an increase in the release of the DCI-IPG mediator and an improvement in insulin sensitivity in women with PCOS is unknown . We conducted a r and omized controlled trial of DCI supplementation vs placebo in 11 women with PCOS who were assessed at 2 time points 6 weeks apart .  Plasma DCI , DCI-IPG release during oral glucose tolerance test ( AUC(DCI-IPG ) ) , and insulin sensitivity ( S(i ) ) by frequently sample d intravenous glucose tolerance test were assessed at baseline and end of study . The study was terminated early because of a sudden unavailability of the study drug . However , in all subjects without regard to treatment assignment , there was a positive correlation between the change in AUC(DCI-IPG)/AUC(insulin ) ratio and the change in S(i ) during the 6-week period ( r = 0.69 , P = .02 ) , which remained significant after adjustment for body mass index ( P = .022 ) and after further adjustment for body mass index and treatment allocation ( P = .0261 ) . This suggests that , in women with PCOS , increased glucose-stimulated DCI-IPG release is significantly correlated with improved insulin sensitivity . The significant relationship between DCI-IPG release and insulin sensitivity suggests that the DCI-IPG mediator may be a target for therapeutic interventions in PCOS Some actions of insulin are mediated by putative inositolphosphoglycan mediators , and a deficiency in D-chiro-inositol-containing inositolphosphoglycan ( DCI-IPG ) may contribute to insulin resistance in women with polycystic ovary syndrome ( PCOS ) . Furthermore , similar effects of DCI and metformin , an insulin-sensitizing drug , have been demonstrated in PCOS women . To determine whether metformin improves insulin actions by increasing biologically active DCI-IPG in women with PCOS , we analyzed DCI-IPG during an oral glucose tolerance test in 19 obese women with PCOS before and after 4 - 8 wk of metformin or placebo .  After treatment , the mean ( + /-SE ) area under the curve ( AUC ) during the oral glucose tolerance test of insulin ( AUC(insulin ) ) decreased significantly more in the metformin group , compared with the placebo group [ -3574 + /- 962 vs. + 1367 + /- 1021 micro IU/min.ml ( -26 + /- 7 vs. + 10 + /- 7 nmol/min.liter ) , P = 0.003 ] , but the AUC of DCI-IPG ( AUC(DCI-IPG ) ) decreased similarly in both groups ( -1452 + /- 968 vs. -2207 + /- 1021%/min , P = 0.60 ) . However , the ratio of AUC(DCI-IPG)/AUC(insulin ) increased by 160 % after metformin and decreased by 29 % after placebo ( P = 0.002 between groups ) . Moreover , metformin seemed to improve the positive correlation between AUC(DCI-IPG ) and AUC(insulin ) but not placebo ( r = 0.32 , P = 0.68 at baseline ; r = 0.52 , P = 0.12 after metformin ; and r = -0.39 , P = 0.30 after placebo ) . We conclude that in obese women with PCOS , metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators , as evidence d by increased bioactive DCI-IPG released per unit of insulin BACKGROUND Obese women with polycystic ovary syndrome ( PCOS ) manifest impaired insulin-stimulated release of a d-chiro-inositol-containing inositolphosphoglycan ( DCI-IPG ) insulin mediator during oral glucose tolerance testing ( OGTT ) , which appears to be restored by the administration of metformin . This suggests that either obesity or PCOS is associated with a defect in the coupling of the stimulation of the insulin receptor by insulin to the release of the DCI-IPG mediator . The objective of this study was to compare the release of bioactive DCI-IPG between normal nonobese women and obese PCOS women during stimulation with two different concentrations of insulin when glucose levels are clamped . METHODS We performed a cross-sectional case-control study at the clinical research center of an academic medical center . A two-step euglycemic-hyperinsulinemic clamp was carried out in 8 nonobese normal and 8 obese PCOS women , during which DCI-IPG bioactivity was monitored . RESULTS At baseline , PCOS women were significantly more obese , hyperinsulinemic , and insulin resistant than the controls . During the clamp studies , DCI-IPG bioactivity increased significantly over the first 45 min of the low-insulin step of the clamp in normal nonobese women ( P = 0.046 ) and then decreased to baseline levels ; DCI-IPG increased again after initiation of the high-insulin step ( P = 0.029 ) . Despite higher insulin levels during the clamp in PCOS women , DCI-IPG bioactivity remained flat throughout both insulin steps and was thus significantly lower than in controls during the initial periods of both steps . CONCLUSIONS The coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in obese PCOS women , which may contribute to the insulin resistance in these women 
    Output:
    