Abnormalities of Insulin Responses After Ambient and Previous Exposure to Glucose in Streptozocin-diabetic and Dexamethasone-treated Rats: Role of Hyperglycemia and Increased B-Cell Demands
Abnormalities of Insulin Responses After Ambient and Previous Exposure to Glucose in Streptozocin-diabetic and Dexamethasone-treated Rats: Role of Hyperglycemia and Increased B-Cell Demands
复制标题
链佐星糖尿病和地塞米松治疗大鼠环境和先前暴露于葡萄糖后胰岛素反应异常：高血糖和 B 细胞需求增加的作用
作者：
V. Grill;M. Rundfeldt
在NIDDM中，B细胞对葡萄糖不敏感。我们研究了这种异常在6-10周龄新生链脲佐菌素糖尿病(STZ)和地塞米松治疗(DMT)大鼠中的特异性和演变。在灌流的胰腺中，不仅表现出周围环境的影响，而且还表现出先前葡萄糖的影响(启动效应)。饲喂STZ的大鼠血糖升高至9.2±0.8 mM，而对照组(C)为5.3±0.2 mM。灌流液中的环境葡萄糖(27 MM)引起显著但降低的总反应(C的11%)，主要是单相的。甘油醛(10 MM)和α-酮基异己酸(KIC)(5 MM)也能诱导STZ和C迅速分泌，而3-异丁基-1-甲基黄嘌呤(IBMX)则引起增强反应，增强反应是C组的3.8倍。灌流液中的环境葡萄糖(27 MM)诱导了正常的第一时相和适度减少的第二时相(未处理大鼠的52%)。DMT大鼠对IBMX有高反应性，这种药物引起的释放量是未治疗大鼠的2.5倍。预先灌流27 mM葡萄糖可使C组的第二个刺激周期的作用增强一倍。这种葡萄糖的启动效应不能在喂食STZ或DMT中表现出来。然而，禁食STZ或胰岛素治疗36h后，再次出现启动诱导，即第二次脉冲葡萄糖引起的胰岛素释放是第一次脉冲的2-3倍。我们的结论是，STZ中B细胞对葡萄糖的部分不敏感改变了胰岛素反应的时间动态，包括启动效应的丧失，受高血糖的影响，并且是营养的，但不是葡萄糖特异性的。DMT的结果表明，对B细胞分泌需求的增加可以导致对非代谢性促分泌剂的高反应性，以及失去葡萄糖诱导的启动，而不会伴随着对环境葡萄糖的敏感性丧失。
In NIDDM, B-cells are insensitive to glucose. We studied the specificity and evolution of this abnormality in 6–10-wk-old neonatally streptozocin-diabetic (STZ) and in dexamethasone-treated (DMT) rats. Not only the effect of ambient but also that of previous glucose (priming effect) was characterized in the perfused pancreas. In fed STZ, blood glucose was elevated to 9.2 ± 0.8 versus 5.3 ± 0.2 mM in control (C) rats. Ambient glucose (27 mM) in the perfusate induced a significant but reduced total response (11% of C) that was predominantly monophasic. Secretion was promptly induced (in <20 s) both in STZ and C. Other nutrients, i.e., glyceraldehyde (10 mM) and α-ketoisocaproic acid (KIC) (5 mM) also induced reduced and monophasic responses, whereas, in contrast, 3-isobutyl-1-methylxanthine (IBMX) induced an enhanced response that was 3.8-fold larger than in C. In DMT, blood glucose was normal (5.4 ± 0.3 mM). Ambient glucose (27 mM) in the perfusate induced a normal first phase and a moderately reduced second phase (52% of untreated rats). DMT rats were hyperresponsive to IBMX, this agent inducing 2.5-fold higher release than in untreated rats. Previous perfusion with 27 mM glucose enhanced twofold the effect of a second stimulation period with glucose in C. This induction of priming by glucose could not be demonstrated in fed STZ or in DMT. However, when STZ were fasted or insulin treated for 36 h, induction of priming reappeared, i.e., the second pulse of glucose evoked 2–3-fold more insulin release than the first pulse. We conclude that partial B-cell insensitivity to glucose in STZ alters time dynamics of the insulin response, includes loss of a priming effect, is influenced by hyperglycemia, and is nutrient but not glucose specific. Results in DMT indicate that increased demands on B-cell secretion can lead to hyperresponsiveness to nonmetabolic secretagogues as well as loss of induction of priming by glucose without concomitant loss of sensitivity to ambient glucose.