Bolaffi J L, Rodd G, Ma Y H, Grodsky G M
Metabolic Research Unit, University of California, San Francisco 94143.
Endocrinology. 1990 Mar;126(3):1750-5. doi: 10.1210/endo-126-3-1750.
In this study we have examined the role of glucagon and somatostatin in regulating glucose-induced desensitization of insulin secretion from rat islets. Measured in batch incubations with medium routinely used to induce three phases of insulin secretion, secreted glucagon levels fell off over 24 h to 20% of peak secretion levels. Although more responsive to various secretagogues, somatostatin secretion also declined to the same degree. Thus, the A- and D-cells desensitize to chronic stimulation as does the B cell. In other experiments, added glucagon (10(-6) M) enhanced glucose (11 X 10(-3) M)-stimulated insulin secretion 34% in the first 3 h; however, islets became insensitive to continuous glucagon by 4 h. The exogenous glucagon did not prevent or delay glucose-induced desensitization of insulin secretion. When glucagon was administered as acute 1-h tests over continuous glucose administration, the degree of B-cell response did not differ in the 1st, 3rd, or 6th hours and appeared to increase in the 21st hour. When islets were perifused continuously with glucose (22 X 10(-3) M) plus 3 X 10(-7) M somatostatin, glucose-induced insulin secretion was suppressed 50% in the first 3 h, but this inhibitory effect disappeared after 6 h. Desensitization was slightly delayed, but not prevented. When somatostatin was administered as acute 1-h tests over continuous glucose perifusion, the B-cell response was relatively constant in the 3rd, 6th, and 21st hours. Results show that 1) islet release of glucagon and somatostatin desensitizes during constant stimulation; and 2) islet release of insulin desensitizes to chronic potentiation or inhibition, respectively, by these hormones. Furthermore, 3) changing B-cell sensitivity to either glucagon or somatostatin cannot account for observed desensitization of insulin secretion with chronic glucose exposure.
在本研究中，我们研究了胰高血糖素和生长抑素在调节葡萄糖诱导的大鼠胰岛胰岛素分泌脱敏中的作用。在常规用于诱导胰岛素分泌三个阶段的培养基中进行批量培养测定，分泌的胰高血糖素水平在24小时内降至峰值分泌水平的20%。虽然对各种促分泌剂更敏感，但生长抑素分泌也下降到相同程度。因此，A细胞和D细胞与B细胞一样，对慢性刺激产生脱敏。在其他实验中，添加的胰高血糖素（10⁻⁶ M）在最初3小时内使葡萄糖（11×10⁻³ M）刺激的胰岛素分泌增加了34%；然而，胰岛在4小时后对持续的胰高血糖素变得不敏感。外源性胰高血糖素并未阻止或延迟葡萄糖诱导的胰岛素分泌脱敏。当在持续给予葡萄糖的过程中进行急性1小时胰高血糖素试验时，B细胞反应在第1、3或6小时没有差异，并且在第21小时似乎增加。当胰岛用葡萄糖（22×10⁻³ M）加3×10⁻⁷ M生长抑素连续灌注时，葡萄糖诱导的胰岛素分泌在最初3小时内被抑制了50%，但这种抑制作用在6小时后消失。脱敏稍有延迟，但未被阻止。当在连续葡萄糖灌注过程中进行急性1小时生长抑素试验时，B细胞反应在第3、6和21小时相对恒定。结果表明：1）在持续刺激期间，胰岛释放的胰高血糖素和生长抑素会脱敏；2）胰岛释放的胰岛素分别对这些激素的慢性增强或抑制产生脱敏；此外，3）改变B细胞对胰高血糖素或生长抑素的敏感性不能解释观察到的慢性葡萄糖暴露时胰岛素分泌的脱敏现象。
