The purpose of this study was to investigate the involvement of growth hormone in the diurnal variation of insulin sensitivity in healthy adults. Afternoon (16:00 hr) or night (23:00 hr) pretreatment with a subcutaneo...The purpose of this study was to investigate the involvement of growth hormone in the diurnal variation of insulin sensitivity in healthy adults. Afternoon (16:00 hr) or night (23:00 hr) pretreatment with a subcutaneous injection of normal saline, human growth hormone to mimic the normal nocturnal rise in growth hormone, or octreotide to inhibit endogenous growth hormone secretion to create a state of relative nocturnal growth hormone deficiency, was given 16 hours before undergoing the modified insulin suppression test in healthy subjects. The morning and evening experiments were separated by an interval of at least 3 days. Thus, each subject was tested on six separate occasions arranged in a random order. A higher value of the steady-state plasma glucose (SSPG) is indicative of lower insulin sensitivity. Plasma glucose, serum insulin, insulin-like growth factor-1, nonesterified fatty acids (NEFA), and metabolic clearance rate of insulin (MCRI) were measured. In the normal saline and human growth hormone groups, SSPG levels were lower in the morning than in the evening. Evening SSPG levels, MCRI, and NEFA concentrations were higher in the participants treated with normal saline and growth hormone than in the octreotide group. Differences in SSPG levels between the morning and evening values were higher in the participants pretreated with normal saline and growth hormone than in those treated with octreotide. A diurnal variation in insulin sensitivity existed in healthy subjects. These results provided direct evidence that the role of growth hormone in regulating insulin sensitivity might be related to changes in the MCRI and the metabolism of NEFA in healthy subjects.展开更多
目的观察宣白承气汤辅助治疗2型糖尿病患者黎明现象的效果,并基于核受体亚家族1组D成员1(Nr1D1)预测宣白承气汤的作用机制。方法2型糖尿病合并黎明现象的患者60例,按随机数字表法分为对照组和观察组各30例。对照组采用强化胰岛素治疗,...目的观察宣白承气汤辅助治疗2型糖尿病患者黎明现象的效果,并基于核受体亚家族1组D成员1(Nr1D1)预测宣白承气汤的作用机制。方法2型糖尿病合并黎明现象的患者60例,按随机数字表法分为对照组和观察组各30例。对照组采用强化胰岛素治疗,研究组采用宣白承气汤联合强化胰岛素治疗。治疗7 d后记录两组治疗前后3 d的空腹血糖(FPG)、早餐后2 h血糖(2 h PG)、空腹血糖与夜间最低点血糖净增值(∂glucose1)、早餐后2 h血糖与空腹血糖净增值(∂glucose2)、日内平均血糖(MBG)、日内血糖波动幅度(MAGE)。通过TCMSP数据库筛选宣白承气汤关键活性成分,利用Cytoscape3.7.2软件构建中药—活性成分—靶点网络图。采用Maestro11.5软件构建Nr1D1虚拟靶点模型,与宣白承气汤活性成分进行分子对接。结果两组治疗后FPG、2 h PG、∂glucose1、MBG、MAGE均较治疗前降低,且观察组低于对照组(P均<0.05)。观察组低血糖发生率低于对照组(P<0.05)。筛选出宣白承气汤45种活性成分,其中,15个活性成分与Nr1D1具有较好的结合活性。其中,来自大黄的5个成分(MOL000554、MOL002280、MOL002260、MOL002259、MOL002288)主要作用于PHE111、ARG172、GLY174、TYR113、LYS122、ARG126、TYR113、GLY174、GLU119、PHE173、SER109、HID112等氨基酸残基组合的活性位点。结论宣白承气汤联合强化胰岛素治疗可显著抑制2型糖尿病患者黎明现象,减少日间血糖波动。宣白承气汤君药大黄中的活性成分可能通过与Nr1D1结合,进而发挥治疗作用。展开更多
文摘The purpose of this study was to investigate the involvement of growth hormone in the diurnal variation of insulin sensitivity in healthy adults. Afternoon (16:00 hr) or night (23:00 hr) pretreatment with a subcutaneous injection of normal saline, human growth hormone to mimic the normal nocturnal rise in growth hormone, or octreotide to inhibit endogenous growth hormone secretion to create a state of relative nocturnal growth hormone deficiency, was given 16 hours before undergoing the modified insulin suppression test in healthy subjects. The morning and evening experiments were separated by an interval of at least 3 days. Thus, each subject was tested on six separate occasions arranged in a random order. A higher value of the steady-state plasma glucose (SSPG) is indicative of lower insulin sensitivity. Plasma glucose, serum insulin, insulin-like growth factor-1, nonesterified fatty acids (NEFA), and metabolic clearance rate of insulin (MCRI) were measured. In the normal saline and human growth hormone groups, SSPG levels were lower in the morning than in the evening. Evening SSPG levels, MCRI, and NEFA concentrations were higher in the participants treated with normal saline and growth hormone than in the octreotide group. Differences in SSPG levels between the morning and evening values were higher in the participants pretreated with normal saline and growth hormone than in those treated with octreotide. A diurnal variation in insulin sensitivity existed in healthy subjects. These results provided direct evidence that the role of growth hormone in regulating insulin sensitivity might be related to changes in the MCRI and the metabolism of NEFA in healthy subjects.
文摘目的观察宣白承气汤辅助治疗2型糖尿病患者黎明现象的效果,并基于核受体亚家族1组D成员1(Nr1D1)预测宣白承气汤的作用机制。方法2型糖尿病合并黎明现象的患者60例,按随机数字表法分为对照组和观察组各30例。对照组采用强化胰岛素治疗,研究组采用宣白承气汤联合强化胰岛素治疗。治疗7 d后记录两组治疗前后3 d的空腹血糖(FPG)、早餐后2 h血糖(2 h PG)、空腹血糖与夜间最低点血糖净增值(∂glucose1)、早餐后2 h血糖与空腹血糖净增值(∂glucose2)、日内平均血糖(MBG)、日内血糖波动幅度(MAGE)。通过TCMSP数据库筛选宣白承气汤关键活性成分,利用Cytoscape3.7.2软件构建中药—活性成分—靶点网络图。采用Maestro11.5软件构建Nr1D1虚拟靶点模型,与宣白承气汤活性成分进行分子对接。结果两组治疗后FPG、2 h PG、∂glucose1、MBG、MAGE均较治疗前降低,且观察组低于对照组(P均<0.05)。观察组低血糖发生率低于对照组(P<0.05)。筛选出宣白承气汤45种活性成分,其中,15个活性成分与Nr1D1具有较好的结合活性。其中,来自大黄的5个成分(MOL000554、MOL002280、MOL002260、MOL002259、MOL002288)主要作用于PHE111、ARG172、GLY174、TYR113、LYS122、ARG126、TYR113、GLY174、GLU119、PHE173、SER109、HID112等氨基酸残基组合的活性位点。结论宣白承气汤联合强化胰岛素治疗可显著抑制2型糖尿病患者黎明现象,减少日间血糖波动。宣白承气汤君药大黄中的活性成分可能通过与Nr1D1结合,进而发挥治疗作用。
