人参糖肽降血糖机制(英文)

目的:研究人参糖肽(GGP)降血糖机制。方法:为了观察GGP对胰岛素分泌和糖酵解的影响,给予GGP后,测定血糖(BG)和肝糖元(LG)含量,及胰岛素、乳酸脱氢酶(LDH)、乳酸(LC)水平。通过测定给予GGP前后肝组织柠檬酸合成酶(CTS)、苹果酸脱氢酶(MDH)、琥珀酸脱氢酶(SDH)和细胞色素氧化酶(CCO)活性变化,推测对糖有氧氧化过程的影响。通过测定肝组织腺苷酸环化酶(AC)活性和cAMP水平,研究人参糖肽对糖代谢的影响及与第二信使cAMP的关系。通过检测肝组织磷酸化酶(PP)活性推测药物对肝糖元代谢的影响。检测药物对细胞膜受体的影响,观察了β-受体阻滞剂普萘洛尔和α-受体阻滞剂酚妥拉明对GGP作用的影响。为了证明GGP与β-受体的结合,观察了GGP与~3H]DHA对北京鸭红细胞膜β-受体的竞争性结合。结果:GGP在降低血糖和肝糖原的剂量下(100,200mg/kg,ip或50,100mg/kg,iv),仅于给药后20分钟,小鼠血浆胰岛素水平即升高,且GGP降低血糖作用可持续16小时;同时,血中LC含量及血和肝组织LDH活性降低。而肝组织AC、CTS、MDH、SDH、COO、PP活力和cAMP水平升高,β-受体阻滞剂普萘洛尔可阻滞GP降低肝糖元作用,GGP可竞争性抑制放射配基~3H]DHA与红细胞膜β-受体的结合,其IC_(50)为63nmol·L~(-1)。结论:GGP为β-受体激动剂,通过第二信使cAM

Hypoglycemic mechanism of ginseng glycopeptide

AIM: To study the hypoglycemic mechanism of ginseng glycopeptide (GGP). METHODS: After administration of GGP, the levels of insulin, lactate dehydrogenase (LDH), lactic acid (LC), and oxygen consumption, as well as blood glucose (BG) and liver glycogen (LG) were measured. Based on these measurement results, the effects of GGP on insulin secretion and anaerobic/aerobic glycolysis were evaluated. Adenylate cyclase (AC) activity and cAMP level were measured to study the effects of GGP on BG and LG metabolism and to determine whether the effects were through second transmitting message system. Propranolol (beta-receptor antagonist) and phentolamine (alpha-receptor antagonist) were used to investigate whether hypoglycemic activity of GGP was through beta- or alpha-adrenoceptor. 3H]DHA (antagonist of beta-adrenoceptor) was used to determine GGP binding affinity to beta-adrenoceptor. Citrate synthetase (CTS), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and cytochrome oxidase (CCO) activities were measured to explore GGP effects on aerobic glycolysis in liver mitochondria. Phosphorylase (PP) activity was measured to study GGP effects on liver glycogen metabolism. RESULTS: cAMP content and AC activity were increased when BG and LG contents in liver of mice decreased. The decrease in liver glycogen induced by GGP was inhibited by pretreatment with propranolol. Radioligand receptor assay showed that GGP was competing in vitro with 3H]DHA to bind to beta-adrenoceptor of duck erythrocyte membrane, and IC50 of GGP was 63 nmol/L. GGP inhibited LDH activity at an appropriate dosage, at which contents of BG and LG could be effectively lowered. GGP also stimulated activities of SDH, MDH, CCO, CTS, and PP. CONCLUSION: The hypoglycemic activity of GGP may be attributed to the enhancement of aerobic glycolysis through stimulation of beta-adrenoceptor and increase of various rate-limiting enzyme activities related to tricarboxylic acid cycle.