Abstract
Background: Insulin resistance is an intrinsic defect of polycystic ovary syndrome (PCOS), and elevated levels of cytosolic free calcium in insulin target cells may cause insulin resistance. To our knowledge, the relationship between intracellular calcium and insulin resistance in PCOS has not been investigated. The purpose of this study was to determine whether the levels of intracelluar calcium are changed and if they have any association with insulin resistance in women with PCOS. Methods: The intracellular calcium levels in the platelets and the insulin sensitivity were measured by fluorescent spectrophotometry and the euglycemic hyperinsulinemic clamp technique, respectively, in 16 women with PCOS and 6 normal cycling women. A 2h, 75 g oral glucose tolerance test was performed to determine the glucose tolerance. Results: The insulin sensitivity measured by the glucose disposal rate(the M-value), was significantly lower in women with PCOS(4.6$\pm$1.5mg/kg/min vs. 7.0$\pm$1.3mg/kg/min, p<0.01), but the intracellular calcium levels were significantly higher in women with PCOS compared to the controls(122.7$\pm$36.7 vs 59.1$\pm$29.3mmol/L, p<0.01). When the women with PCOS were divided into the overweight or obese(n=9, BMI ≧23kg/m2) and lean(n=7, BMI<23kg/m2) groups, both groups had significantly lower M values compared to the control subjects(3.9$\pm$1.3, 5.5$\pm$1.2 vs. 7.0$\pm$1.3μmg/kg/min, p<0.001), and these levels between the overweight/obese and lean PCOS groups showed a significant difference(p<0.001). The overweight/ obese and lean women with PCOS had significantly higher levels of intracellular calcium compared to the control subjects(131.3$\pm$39.6, 111.7$\pm$31.8 vs. 59.1$\pm$29.3nmol/L, p<0.01), but these levels did not differ significantly between the overweight/obese and lean women with PCOS. The intracellular calcium levels showed a significant positive correlation with age, and a negative correlation with the M value(r=-0.55, p<0.05). The BMI-adjusted partial correlation showed marginal significance between elevated levels of intracellular calcium and insulin sensitivity (r=-0.47, p=0.07). Conclusion: Women with PCOS showed both insulin resistance and increased levels of intracellular calcium compared to the control subjects. Increased levels of intracellular calcium were associated with insulin resistance in women with PCOS(J Kor Diabetes Assoc 28:101-110, 2004).
연구배경: 인슐린저항성은 다낭성난소증후군(PCOS)의 주된 병인이며, 인슐린 표적 세포내 칼슘농도의 과다한 증가는 포도당 운반을 감소시키며 인슐린의 신호전달을 저해하여 인슐린저항성의 유발에 관여할 것으로 생각된다. 그러나 현재까지 다낭성난소증후군에서 인슐린저항성과 세포내 칼슘 농도의 증가사이의 연관성에 대한 보고는 없다. 본 연구는 다낭성난소증후군에서 세포내 칼슘농도의 변화가 있는지 관찰하고 이러한 변화가 인슐린저항성과 관련되는지 알아보고자 시행되었다. 방법: PCOS 16명과 정상대조군 6명을 대상으로 하여 정상혈당클램프 검사와 75그람 경구당부하검사를 시행하여 인슐린감수성지표(M-value)를 판정하였다. 말초 혈액에서 혈소판을 분리하여 형광분광광도기를 이용하여 세포내 칼슘농도를 측정하였다. 결과: PCOS 여성에서 M-value는 정상대조군에 비해 유의하게 낮았으며(4.6$\pm$1.5 vs 7.0$\pm$1.3 mg/kg/min, p<0.01), 세포내칼슘 농도는 유의하게 높았다(122.7$\pm$ 36.7 vs 59.1$\pm$29.3mmol/L, p<0.01). PCOS를 체질량지수 23kg/m2를 기준으로 구분하였을 때, M-value는 overweight/obese(n=9) 및 lean PCOS(n=7)에서 모두 정상대조군에 비해 유의하게 낮았으며(3.9$\pm$1.3, 5.5$\pm$1.2 vs 7.0$\pm$1.3mg/kg/min, p<0.001), overweight/ obese PCOS와 lean PCOS사이도 통계적으로 유의한 차이가 있었다(p<0.001). 세포내칼슘 농도는 overweight/obese 및 lean PCOS에서 정상대조군에 비해 유의하게 높았으며(131.3$\pm$39.6, 111.7$\pm$31.8 vs 59.1$\pm$ 29.3nmol/L, p<0.01), overweight/obese PCOS와 lean PCOS사이에 유의한 차이는 없었다. 세포내칼슘 농도는 연령과 유의한 양의 상관관계가 있었으며, M-value와는 유의한 음의 상관관계를 보였다(r=-0.55, p<0.05). 체질량지수를 보정한 후 세포내칼슘 농도는 M-value와 음의 상관성의 경향을 보였다(r=-0.47, p=0.07). 결론: 다낭성난소증후군 여성은 인슐린저항성을 보이고 세포내칼슘농도가 증가되어 있었으며, 증가된 세포내 칼슘 농도는 인슐린저항성과 관련될 것으로 생각된다.