那格列奈-OGTT测定LADA患者及其一级亲属的胰岛β细胞功能

目的　以那格列奈 (NG) 口服葡萄糖耐量试验 (OGTT)方法评估LADA患者及其一级亲属(FDR)胰岛 β细胞功能。 方法　 9例正常人 1周内先后行NG OGTT、精氨酸刺激试验和普通OGTT ,测定各时点的胰岛素和血糖水平。观察NG OGTT中胰岛素净增值与血糖净增值的比值 (ΔI/ΔG)和精氨酸刺激试验中急性期胰岛素释放 (AIR)的相关性 ,比较NG OGTT和普通OGTT的差异和关联。 10例FDR行NG OGTT和普通OGTT ,LADA和 2型糖尿病 (DM)患者各 9例仅行NG OGTT ,比较 4组研究对象在NG OGTT中的早期相胰岛素释放和胰岛 β细胞储备功能 ,并用HOMA公式评估胰岛素抵抗。 结果　 (1)NG OGTT中胰岛素释放速率 (IRR)最高点为糖负荷后 3 0min ,且该时点的ΔI3 0 /ΔG3 0 与精氨酸刺激试验的AIR呈正相关 (Rs =0 .674,P <0 .0 5 ) ;NG OGTT中各时点胰岛素曲线下面积和胰岛素释放倍增值均高于普通OGTT(均P <0 .0 1)。 (2 )LADAFDR在NG OGTT中ΔI3 0 /ΔG3 0 (2 3 .0± 13 .2 )mU/mmol和 3 0min处IRR (1.3± 0 .8)mU·L-1·min-1均低于正常 (P <0 .0 5 ) ,而HOMA IR指数高于正常 (2 .2± 0 .7vs 1.5± 0 .7,P <0 .0 5 )。 (3 )LADA和 2型DM患者的HOMA IR指数分别为 (2 .9± 0 .9和 5 .0± 3 .4) ,均高于正常 (1.5± 0 .7) (2型DM >LADA >正常     

短期胰岛素强化治疗对新诊断2型糖尿病患者不同时相胰岛素分泌的影响

目的应用高葡萄糖钳夹技术评估短期胰岛素强化治疗对新诊断的2型糖尿病(T2DM)患者胰岛素分泌时相的影响。方法对12例正常人及6例新诊断糖尿病患者行高葡萄糖钳夹试验评价胰岛β细胞功能。6例糖尿病患者进行2周胰岛素强化治疗后重复高葡萄糖钳夹试验。结果正常组第一时相胰岛素分泌(1PH)257±36mU/L,第二时相胰岛素分泌(2PH)63±5mU/L,最大胰岛素分泌80±6mU/L。糖尿病组治疗前胰岛素分泌分别为95±19mU/L、34±9mU/L、39±12mU/L显著低于正常组(P均<0·01)。糖尿病组治疗后与治疗前相比,1PH显著改善(135±27vs95±19mU/L,P=0·01),2PH及最大胰岛素分泌量轻度改善,但差异无统计学意义(40±9mU/Lvs34±9mU/L,P=0·09;46±11mU/Lvs39±12mU/L,P=0·08)。结论对新诊断的T2DM患者2周胰岛素强化治疗能够明显改善胰岛素1PH分泌,并对2PH分泌及最大分泌可能也有改善作用。     

纳格列奈-口服葡萄糖耐量试验对检测正常人胰岛β细胞功能的评价

目的 优化纳格列奈-口服葡萄糖耐量试验(NG-OGTT)评估胰岛β细胞功能的方法.方法 对24例健康志愿者进行NG-OGTT,测定各设定时间点(-15、0、10、20、30、45、60及120 min)的胰岛素和血糖水平.胰岛素测定采用放射免疫法.观察NG-OGTT中胰岛素释放的峰值,胰岛素释放倍增值(MVI),各设定时间点的胰岛素释放曲线下面积(AUCIns)、胰岛素释放速率(IRV)、胰岛素净增值与血糖净增值的比值(△I/△G),筛选出NG-OGTT中最能反映胰岛β细胞分泌与储备功能的时间点.结果 (1) 正常人在NG-OGTT中反映胰岛β细胞早期相分泌功能的胰岛素释放峰值(90.50 mU/L)与IRV(2.75 mU·L-1·min-1)的达峰时间均在糖负荷后30 min;(2)其△I/△G的达峰时间虽在糖负荷后45 min(56 mU/mmol),但45 min时该值的升高主要由血糖的快速降低引起;(3) 反映β细胞储备功能的MVI(18.8)的达峰时间亦在糖负荷后30 min;(4) 其AUCIns在60 min时与120 min具有显著性相关(r=0.901,P=0.000).结论 糖负荷后采用-15、0、30和60 min 4个采血点,能反映β细胞早期相分泌功能及储备功能,方法简便.     

空腹血糖异常人群胰岛素分泌功能及胰岛素抵抗状态的探讨

目的　探讨空腹血糖异常人群的胰岛素分泌及胰岛素抵抗状态。　方法　选择包钢糖尿病普查中复查口服葡萄糖耐量试验 (OGTT) 3985例 ,分为 6组 :正常糖耐量 (NGT)组 2 5 88例 ,异常空腹血糖 (IFG)组 2 72例 ,糖耐量减低 (IGT)组 4 4 9例 ,空腹血糖异常伴糖耐量减低 (IFG/ IGT)组116例 ,新诊断糖尿病 (DM1)组 338例 ,已知糖尿病 (DM2 )组 2 2 2例。测腰围、体重指数、血压、血脂及血浆胰岛素 ,应用稳态模式胰岛素抵抗指数 (HOMA- IR)作为胰岛素抵抗指标 ,稳态模式胰岛 β细胞功能指数 (HBCI)及胰岛素分泌指数 (IS)作为胰岛素分泌指标 ,并对 6组患者的这些指标及临床特征 ,进行对比分析。　结果　与 NGT组比较 ,IFG组 HOMA- IR(1.4 6± 0 .6 0 ,1.0 6± 0 .6 4 ,t=- 6 .716 ,P<0 .0 0 1)、空腹胰岛素 (FINS) (17.90± 10 .0 6 ,15 .79± 10 .94 ,t=- 2 .0 71,P=0 .0 39)增高 ,HB-CI(4.6 5± 0 .6 0 ,5 .2 7± 0 .76 ,t=3.399,P<0 .0 0 1)及 IS(0 .86± 0 .6 0 ,0 .99± 0 .6 2 ,t=2 .36 6 ,p=0 .0 18)降低 ;IGT组 HOMA- IR(1.39± 0 .5 8,t=4 .6 98) ,FINS(2 1.2 7± 15 .39,t=4 .4 93)、2 - h胰岛素(6 0 .84± 37.86 ,t=8.4 82 )、HBCI(5 .4 7± 0 .79,t=2 .6 98)、IS(1.2 5± 0 .6 1,t=4 .0 34,P值均 <0     

左旋精氨酸刺激试验评价遗传背景对正常糖耐量者和初诊糖尿病患者胰岛β细胞功能的影响

目的 探讨遗传背景对左旋精氨酸(L-ARG)刺激后胰岛β细胞第一时相分泌功能的影响.方法 检测201例L-ARG刺激前后胰岛素值,其中有家族史初诊2型糖尿病患者(FH+DM)61例、无家族史初诊2型糖尿病患者(FH-DM)55例、有家族史正常糖耐量者(FH+)31例、无家族史正常糖耐量者(FH-)54例.以HOMA胰岛素抵抗指数(HOMA-IR)评价胰岛素抵抗.结果 校正性别、年龄、BMI后,(1)糖尿病组(FH+DM和FH-DM)TC、TG、空腹血浆血糖(FPG)、糖负荷后2 h血糖、空腹胰岛素(Fins)、HOMA-IR明显高于糖耐量正常组(FH+和FH-),胰岛素峰值倍数明显低于糖耐量正常组,P<0.05;(2)4组胰岛素均2 min达分泌峰值,4 min开始下降;(3)FH+组胰岛素峰值倍数较FH-组下降20.8%,分别为7.27与9.18倍,P<0.05;(4)FH+DM组2 min胰岛素分泌峰值、HOMA-IR、患病年龄明显低于FH-DM组(P<0.05),两组峰值倍数分别为5.18与5.31倍,差异无统计学意义(P>0.05);(5)FH+DM组胰岛素峰值倍数较FH-组下降了 43.6%(P<0.05).结论 2型糖尿病早期,尽管胰岛素抵抗表现不显著,遗传背景却使胰岛β细胞第一时相分泌功能减退;而无遗传背景者,胰岛素抵抗使胰岛素第一时相分泌下降相对缓慢.     

高血糖状态对2型糖尿病患者胰岛β细胞分泌功能的影响

目的　了解葡萄糖毒性对胰岛 β细胞分泌功能的影响。 　方法　观察 118例 2型糖尿病 (T2DM)患者在不同血糖状态下 ,胰岛 β细胞分泌对口服葡萄糖耐量试验 (OGTT)和胰高血糖素刺激试验 (GST)的反应能力。　结果　胰岛 β细胞的分泌功能在OGTT随空腹血糖的升高而下降(P <0 0 1) ;在GST随血糖升高而增强 ,达 9mmol/L以上时维持在高水平。OGTT胰岛素释放倍数与胰岛素抵抗指数 (HOMA IR)呈负相关 (P <0 0 1) ,GST胰岛素释放倍数与胰岛 β细胞功能指数(HOMA β)呈正相关 (P <0 0 1)。 　结论　葡萄糖毒性干扰胰岛 β细胞功能的判断 ,血糖过高抑制OGTT时的胰岛素释放 ,GST受此影响小 ,能较客观反映胰岛 β细胞功能状态。     

非诺贝特对高甘油三酯血症人群胰岛素抵抗和胰岛β细胞分泌功能的影响

目的观察非诺贝特对高甘油三酯(TG)血症人群的胰岛素抵抗和胰岛β细胞分泌功能的影响。方法正常糖耐量、高TG血症(TG≥12．3 mmol/L)患者12例(HTG组),予非诺贝特200 mg/d治疗3个月,于治疗前后应用高葡萄糖钳夹技术评价胰岛素敏感性和胰岛β细胞功能。并与正常糖耐量、正常血脂志愿者12名(NC组)进行比较。结果HTG组胰岛素敏感性指数(ISI)显著低于NC组;第一时相胰岛素分泌(1PH)稍低于NC组;第二时相胰岛素分泌(2PH)和最大胰岛素分泌(INS120-150)均明显高于NC组。HTG组非诺贝特治疗后,ISI较治疗前显著升高(18．35±1．76 vs 9．40±1．76,P＜0．01);1PH变化无统计学意义[(247．7±32．9)mIU/L vs (225．7±36．7)mIU/L,P=0．94];2PH和INS120-150较治疗前降低[分别为(73．2±9．0)mIU/L vs (106．0±11．3)mlU/L,p=0．014;(89．2±8．9)mIU/L vs (141．6±13．8) mIU/L,P=0．005]。结论非诺贝特调脂治疗能显著改善高TG血症人群的胰岛素抵抗及高葡萄糖钳夹试验中的胰岛素分泌。     

OGTT 0.5h血糖切点值在诊断糖尿病及糖尿病前期中的临床意义

目的 确定口服葡萄糖耐量试验(OGTT)负荷后0.5 h血糖(0.5 hPG)诊断糖尿病和糖尿病前期(preDM)的切点值及0.5 hPG与β细胞功能、胰岛素敏感性的关系.方法 4 351名受试者行OGTT,以2008年美国糖尿病协会(ADA)糖代谢异常诊断标准为参考标准,应用受试者工作特征(ROC)曲线分析0.5 hPG诊断糖尿病和preDM的切点值.将受试人群先按照2008年ADA糖代谢异常诊断标准分为正常糖耐量组(NGT组)、preDM组、糖尿病组,再按研究得出的切点值将NCT组中0.5 hPG＜诊断preDM切点值者作为N-NGT组,0.5 hPG≥诊断preDM切点值者则为H-NGT组;将preDM组中0.5 hPG＜诊断糖尿病切点值者作为N-preDM组,0.5 hPG≥诊断糖尿病切点值者则为H-preDM组.比较5组的血糖、胰岛素水平、胰岛素敏感性、早时相及总时相胰岛素分泌功能等指标,并进行0.5 hPG与上述指标的相关性分析.结果 以2008年ADA糖尿病诊断标准为参考标准,由ROC得出诊断糖尿病最佳的0.5 hPG切点值为10.79 mmol/L,灵敏性为80.6％,特异性为86.1％,曲线下面积0.92±0.00;以2008年ADA关于preDM的诊断标准为参考标准,得出诊断preDM最佳的0.5 hPG切点值为8.69 mmol/L,灵敏性为74.7％,特异性为70.9％,曲线下面积0.79±0.01.随着糖代谢异常的进展,5组的早时相胰岛素分泌指数、30 min处置指数(DI30)及总时相胰岛素分泌指数、120 min处置指数(DI120)、稳态模型评估-胰岛β细胞分泌指数(HOMA-β)逐渐下降(F =412.25～2 113.02,P均＜0.01),而稳态模型评估-胰岛素抵抗指数(HOMA-IR)逐渐升高(F=151.78,P＜0.01).0.5 hPG与HOMA-β(r =-0.69)、胰岛素生成指数(r=-0.71)、Matsuda胰岛素敏感指数(r=-0.21)、早时相胰岛素分泌指数(r =-0.48)、总时相胰岛素分泌指数(r=-0.54)、DI30(r=-0.62)、DI120(r =-0.70)呈负相关(P均＜0.01),与HOMA-IR呈正相关(r=0.34,P＜0.01).结论 0.5 hPG≥10.79 mmol/L可诊为糖尿病,8.69 mmol/L≤0.5 hPG＜ 10.79 mmol/L可诊为preDM.0.5 hPG在一定程度上可反映胰岛素敏感性及胰岛β细胞功能,随着0.5 hPG的升高,胰岛素敏感性逐渐下降,早时相胰岛素分泌缺陷亦逐渐加重,这种相关性独立于胰岛素敏感性.     

胰岛素抵抗是糖耐量正常人群糖耐量恶化的最重要危险因素

目的　探讨胰岛素抵抗和胰岛素分泌对糖耐量正常人群糖耐量恶化的影响。方法　以口服葡萄糖耐量试验 (OGTT)做人群普查 ,确定糖耐量正常者 (NGT)〔空腹血糖 (FPG) <5 .8mmol/L及 2小时血糖 (PG2h) <6 .7mmol/L〕12 5例 ,测定血浆胰岛素。 6年后随访再以OGTT确定该人群糖耐量状态 ,以稳态模型 (HomaModel)公式评估胰岛素抵抗 (IR)、胰岛素分泌功能 (IS) ,并分析其对糖耐量恶化的影响。结果　 12 5例糖耐量正常人中 ,6年后 2 3例糖耐量恶化〔IGT 2 0例 ,糖尿病(DM) 3例〕。糖耐量恶化者初访时FPG、PG2h与糖耐量仍正常者无明显差别 ,但前者 1小时血糖(PG1h)、1小时胰岛素 (INS1h)均较后者高 (P <0 .0 5 ) ,且前者较肥胖 (P <0 .0 5 )及胰岛素敏感性更差 (P <0 .0 5 )。按胰岛素敏感性三分变量分组 ,胰岛素敏感性最差组的糖耐量恶化率为胰岛素敏感组的 3倍 (34.2 %比 11.9%和 9.5 % ,P <0 .0 5 )。Logistic回归结果显示初访时的胰岛素敏感性与糖耐量恶化显著负相关 ,而年龄、性别、PG2h、体重指数 (BMI)及IS均与糖耐量恶化相关不显著。结论胰岛素抵抗是糖耐量正常人群糖耐量恶化最重要的危险因素     

中老年正常糖耐量人群胰岛β细胞功能分析

目的 分析中老年正常糖耐量人群血糖水平与胰岛B细胞分泌功能的关系.方法 选择上海市部分社区流行病学调研2095例居民,根据口服葡萄糖耐量试验(OGTT)、空腹血糖(FPG)和餐后2 h血糖(2 hPG)结果,将受检者分为正常糖耐量、糖耐量减低(IGT)、空腹血糖受损(IFG)、糖耐量减低合并空腹血糖受损(IFG/IGT)及糖尿病组.再将正常糖耐量者按年龄及空腹血糖值进行分组,观察稳态胰岛β细胞功能指数(HBCI),并对各组年龄、血糖与胰岛β细胞分泌功能指标进行统计学分析.结果 (1)随着年龄的增长,FPG逐渐升高,40～49岁、50～59岁及60～69岁组分别为(5.00±0.47)mmol/L、(5.09±0.44)mmol/L及(5.17±0.48)mmol/L,50～59岁组与40～49岁组比较(t=2.727,P<0.01)、60～69岁组与50～59岁组比较(t=2.303,P<0.05),均差异有统计学意义,但空腹胰岛素(FINS)值变化无明显规律;(2)随着年龄的增长,HBCI值呈下降趋势(F=33.75,P<0.05);(3)FPG≥5.0 mmol/L组较<5.0 mmol/L组HBCI值下降,分别为4.39±0.58和4.22±0.70,差异有统计学意义(t=2.974,P<0.05).结论 中老年正常糖耐量者随着年龄增长,空腹血糖增高;当空腹血糖≥5.0 mmol/L时,可能存在胰岛β细胞分泌功能异常.     

Succesful transplantation of human islets in recipients bearing a kidney graft

Aims/hypothesis: Islet transplantation is a minimally invasive approach to curing Type I (insulin-dependent) diabetes mellitus. Success has recently been reported in patients receiving solitary islet transplants but the outcome in patients receiving islets together with, or after, kidney transplants has been limited and unpredictable. Methods: Here we report successful islet transplantation in a cohort of 15 patients with Type I diabetes who were followed for at least 1 year after islet transplantation, after having already received kidney allografts because of end-stage nephropathy. Results: C-peptide after transplantation was higher than 0.17 nmol/l in all 15 recipients, reflecting the absence of primary non-function. Insulin requirement was reduced by over 50 % in all but one patient, and insulin independence was achieved in 10 (66 %) recipients, five of whom now have stable, prolonged insulin independence, well controlled fasting glycaemia, a substantial first-phase and normal second-phase response to glucose, normal insulin sensitivity (HOMA analyses) and HbA_{1 c} of under 6.2 % (33, 26, 18, 13 and 12 months after transplantation respectively). Of importance for patient management, an assessment of fasting blood glucose and proinsulin values following overnight withdrawal of insulin administration one month after transplantation was a potent predictor of insulin independence, and could be used to decide patients who should have further islet preparations. Conclusion/interpretation: These findings support the use of islet transplantation as a cure for Type I diabetes in patients with severe complications. [Diabetologia (2002) 45: 77–84] Received: 23 April 2001 and in revised form: 30 July 2001     

多囊卵巢综合征患者血清Ghrelin水平测定及其意义

目的探讨血清生长素(Ghrelin)与多囊卵巢综合征(PCOS)的关系。方法选择PCOS患者35例(P-COS组)及正常体检者33例(对照组),两组服75 g葡萄糖粉后,分别检测空腹与服糖1、2 h血脂,基础血激素(雌激素、孕激素、卵泡刺激素、黄体生成素、泌乳素、睾酮、雄烯二酮)及Ghrelin水平,计算BMI、腰臀比(WHR)、胰岛素抵抗指数及敏感指数。结果 PCOS组BMI、TG、HDL、胰岛素抵抗指数、空腹胰岛素、Ghrelin、睾酮及雄烯二酮在空腹与服糖1、2 h均低于对照组(P<0.05或<0.01)。相关分析显示,血清Ghrelin与BMI、WHR、雄激素、雄烯二酮、空腹血糖呈负相关(r分别为-0.504、-0.336、-0.440、-0.432、-0.414,P均<0.05),与HDL呈正相关(r=0.357,P<0.05)。结论血清Ghrelin可能在PCOS的病理生理过程中发挥作用。     

The effect of placental lactogen (HPL) on glucose-induced insulin release

Summary The possible effect of placental lactogen on the process of insulin secretion was investigated in rabbits by examining its action upon glucose-induced insulin secretion. Glucose injection (0.5 g/kg body weight) resulted in a prompt insulin response. When placental lactogen (5 mg/kg body weight) and glucose were injected simultaneously, no significant changes in blood glucose levels were observed as compared to those after glucose alone. Plasma insulin levels 5 min after the combined injection were higher than after glucose alone and the total insulin response appeared to be an additive effect of the two stimulating agents. Insulin secretionin vitro by pieces of pancreatic tissue from rabbits has been studied with and without the addition of glucose and HPL. The dynamics of insulin secretion were examined by sequential exposure of the same pieces of pancreatic tissue. After 60 min of preincubation, 25 μg/ml of partially purified HPL plus glucose significantly increases insulin release. It is suggested that the increase of B-cell secretion during pregnancy could be due, at least in part, to the stimulation of endogenous production of chorionic growth hormone. Traduzione a cura di G. U.     

Blutglucose und Seruminsulin nach oraler Applikation von Glucose und Stärkesirup in unterschiedlicher Dosierung

Zusammenfassung Bei 6 Gruppen stoffwechselgesunder Personen (8–14 Probanden pro Gruppe) wurden orale Belastungen mit 50 g, 100 g oder 200 g Glucose bzw. Stärkehydrolysat durchgeführt. Die Blutglucoseveränderungen waren von der Art und der Menge der verabreichten Kohlenhydrate weitgehend unabhängig. Bei den Seruminsulinwerten war dagegen eine deutliche Beziehung zur verabreichten Kohlenhydratmenge vorhanden. Nach 50 g Kohlenhydraten betrug der Anstieg des Seruminsulins etwa 50 E/ml, nach 100 g Kohlenhydraten etwa 90 100 E/ml. Eine weitere Erhöhung der verabreichten Kohlenhydratmenge bewirkt zwar keine weitere Steigerung der Maximalwerte, jedoch war die Normalisierung der Seruminsulinwerte stark verzögert. Aus dem Verhalten der Seruminsulinwerte nach Verabreichung großer Kohlenhydratmengen kann geschlossen werden, daß trotz Normalisierung der Blutglucosewerte die Glucoseresorption nach 120 min noch nicht abgeschlossen ist. 100 g Glucose oder Stärkesirup sind nach diesen Ergebnissen für die orale Belastungsprobe zu diagnostischen Zwecken besser geeignet als 50 g Kohlenhydrate. Erst bei Einnahme von 100 g Kohlenhydraten wird die Insulinsekretion ausreichend stimuliert, was besonders für den wichtigsten Zeitpunkt der Untersuchung — zwei Stunden nach Einnahme der Kohlenhydrate von wesentlicher diagnostischer Bedeutung ist.

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Blood glucose and serum insulin after oral loading with glucose and starch syrup in varying doses

Summary 6 groups consisting of 8–14 healthy control persons received 50 g, 100 g or 200 g of glucose or of a starch-hydrolyzate preparation by mouth. Blood sugar changes were largely independent of the type or amount of carbohydrate given. Serum insulin values, however, showed a definite correlation with the amount of ingested carbohydrate. After 50 g of carbohydrate the rise of serum insulin was about 50 U/ml; after 100 g of carbohydrate it reached 90–100 U/ml. There was no further rise of maximal values after ingestion of larger amounts of carbohydrate, but the normalization of insulin levels was markedly delayed. From the pattern of serum insulin levels after ingestion of large amounts of carbohydrates, it can be concluded that glucose absorption is not finished at 120 min despite normal blood glucose values. As indicated by these results, 100 g of glucose or starch-syrup is better suited for diagnostic purposes than is 50 g of carbohydrates. Only the ingestion of 100 g of carbohydrates stimulates insulin release sufficiently, which is of special diagnostic interest for the most significant interval of the test, i.e. 2 h after ingestion of the carbohydrate load.

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Glucose sanguin et insuline sérique aprés charge orale de glucose et de sirop d'amidon à différentes doses

Résumé 6 groupes de 8–14 sujets en bonne santé ont reu 50 g,ç 100 g ou 200 g de glucose ou d'une préparation d'hydrolysat d'amidon par voie orale. Les modifications de la glycémie étaient largement indépendantes du type ou de la quantité d'hydrates de carbone administrés. Les valeurs de l'insuline sérique, par contre, montraient une corrélation nette avec la quantité d'hydrates de carbone ingérés. Aprés 50 g d'hydrates de carbone, l'augmentation de l'insuline sérique était environ de 50 U/ml; aprés 100 g d'hydrates de carbone, elle atteignait 90–100 U/ml. Il n'y avait pas d'autres augmentations des valeurs maximales aprés ingestion de quantités plus grandes d'hydrates de carbone, mais la normalisation des taux d'insuline était nettement retardée. A partir du comportement des taux d'insuline sérique aprés ingestion de grandes quantités d'hydrates de carbone, on peut conclure que la résorption du glucose n'est pas terminée à 120 min malgré des valeurs normales de glucose sanguin. Comme l'indiquent ces résultats, 100 g de glucose ou de sirop d'amidon conviennent mieux à des buts diagnostiques que 50 g d'hydrates de carbone. Seulement l'ingestion de 100 g d'hydrates de carbone stimule suffisamment la sécrétion d'insuline, ce qui est d'un intérêt diagnostique spécial pour le moment le plus important du test, c'est-à-dire 2h aprés l'ingestion d'une charge d'hydrates de carbone.

     

The stimulus-secretion coupling of glucose-induced insulin release XLVI. Physiological role of l-glutamine as a fuel for pancreatic islets

Exogenous L-glutamine is actively metabolized in rat pancreatic islets. The rate of L-glutamine deamidation largely exceeds the rate of glutamate conversion to γ-aminobutyrate and α-ketoglutarate. The latter conversion occurs in part by oxidative deamination, and in part by transamination reactions coupled with the conversion of 2-keto acids (pyruvate, oxaloacetate), themselves derived from the metabolism of glutamine, to their corresponding amino acids (alanine, aspartate). An important fraction of malate formed from α-ketoglutarate leaves the Krebs cycle and is converted to pyruvate, this process being apparently associated with the induction of a more reduced state in cytosolic redox couples. L-Glutamine abolishes the oxidation of endogenous fatty acids and stimulates lipogenesis. A sparing action of L-glutamine upon the utilization of endogenous nutrients is documented by the fact that the glutamine-induced increase in O₂ consumption is much lower than expected from the rate of ¹⁴CO₂ output from islets exposed to L-[U-¹⁴C]glutamine. L-Glutamine, although decreasing K⁺conductance, fails to stimulate insulin release both in the absence and presence of D-glucose. It is proposed that L-glutamine represents a major fuel for pancreatic islets under physiological conditions.     

Stimulation of insulin release by an organic calcium agonist

Summary The calcium-agonist 4-[2-(difluoromethoxy)phenyl]-1,4,5,7-tetrahydro-2-methyl-5-oxo-furo[3,4-b]pyridine-3-carboxylic acid ethylester provoked, in the 1.0–100 mol/l range, a dose-related increase of glucose-stimulated insulin release by rat pancreatic islets. A fixed concentration of the drug (50 mol/l) caused a shift to the left of the sigmoidal curve relating insulin output to glucose concentration. The drug failed to affect insulin release evoked, in the absence of Ca²⁺, by the combination of Ba²⁺ and theophylline. The enhancing action of the calcium-agonist upon insulin release was rapid and sustained, and coincided with stimulation of both ⁴⁵Ca net uptake and ⁴⁵Ca efflux, the latter phenomenon being abolished in the absence of extracellular Ca²⁺. It is concluded that the gating of Ca-channels, as presumably provoked by the calcium-agonist, simulates the stimulant action of glucose upon both Ca influx into and insulin release from the pancreatic islets.     

Insulin and glucagon release in the diabetic Chinese hamster: Differences among inbred sublines

Summary Release of insulin and glucagon from perfused pancreases in vitro of 40 normal male and female Chinese hamsters (from one inbred subline) and 110 male and female diabetic hamsters (from three inbred sublines) was measured in response to glucose plus arginine, theophylline alone, or potassium alone, in order to determine if differences in hormone secretion exist among different diabetic sublines. Glucose plus arginine and potassium produced subnormal insulin responses in all three diabetic sublines, whereas theophylline induced normal or above normal insulin responses. Excessive glucagon release was consistently seen in only one diabetic subline. The female normal animals showed greater insulin release than the male normal hamsters in response to glucose plus arginine. This sex difference was not seen in the diabetic animals.     

The role of calcium in glucagon release,interactions between glucose and calcium

Summary The interrelationships between glucose and calcium in glucagon release were investigated using the dynamic system of the in vitro perfused rat pancreas. When calcium deprivation was induced in the presence of fixed concentrations of glucose prevailing throughout the experiments (3.3, 5.5, 8.3 and 16.6 mM), an enhancement of glucagon release invariably occurred, the shape and amplitude of such response differing in relation to the environmental glucose concentration. Such enhancement of glucagon release was readily reversible upon restoration of normal calcium levels. By contrast, during the period of calcium deprivation itself, glucagon release was little influenced by either raised (from 3.3 to 16.6 mM) or decreased (from 16.6 to 3.3 mM) glucose concentrations. These results clearly indicate that calcium plays, at least, a dual role — both inhibitory and permissivein glucagon secretion, but the intimate mechanisms by which calcium exerts such a dual action are at present unknown.     

Stimulus-secretion coupling of hypotonicity-induced insulin release in BRIN-BD11 cells

The stimulus-secretion coupling for hypotonicity-induced insulin release was investigated in BRIN-BD11 cells. A 50 mM decrease in extracellular NaCI caused a twofold increase in insulin release. The release of insulin evoked by hypotonicity progressively decreased in an exponential manner. The response to extracellular hypotonicity displayed a threshold value close to 20 mOsmol/L and amaximal response at about 70 mOsmol/L. Hypotonicity also caused a rapid increase in cell volume followed by a regulatory volume decrease (RVD), cell membrane depolarization with induction of spike activity, and a rise in cytosolic Ca²⁺ concentration. 5-Nitro-2-(3-phenylpropylamino) benzoate inhibited the secretory response to hypoosmolarity, failed to affect the early increase in cell volume but prevented the RVD, and suppressed the hypotonicity-induced plasma membrane depolarization. Insulin release provoked by hypotonicity was inhibited by verapamil, absence of Ca²⁺, thapsigargin, furosemide, tributyltin, and diazoxide. On the contrary, tolbutamide augmented modestly insulin release recorded in the hypoosmolar medium. Last, a rise in extracellular K⁺ concentration, while augmenting basal insulin output, failed to affect insulin release in the hypoosmolar medium. Thus, the insulin secretory response to hypotonicity apparently represents a Ca²⁺-dependent process triggered by the gating of volume-sensitive anion channels with subsequent depolarization and gating of voltage-sensitive Ca²⁺ channels.