AGING AND THE PANCREAS

衰老与以下疾病的发生率增加有关： 2型糖尿病在研究了 与年龄相关的胰岛素分泌下降，随着年龄的增长， 似乎β细胞分泌胰岛素的异常， 糖尿病患者的胰腺是正常情况下的夸大 衰老过程，再加上对胰岛素释放的需求增加， 在胰岛素抵抗的情况下。最令人感兴趣的是 这些变化是可以逆转的。我们对待年轻人 （3个月）和老年（23个月）Wistar大鼠， 人重组GLP-1（1.5 pmol/kg体重， 分钟），一种天然存在的肠肽，使用ALZET 渗透泵（1003 D）植入颈部皮下5 天胰岛素mRNA在GLP-1输注组中增加了3倍。 动物即使是mRNA含量较低的老年大鼠， (50%低）的胰岛素水平比年轻大鼠高3倍， 胰岛素mRNA。随着年龄的增长，胰岛素分泌异常， 也通过这种治疗正常化。很有趣的是， 在长期治疗后， GLP-1。GLP-1导致干细胞增殖， 分化成胰岛素分泌细胞。这发生在干细胞中， 腺泡和导管组织。这一现象并未表现出来 任何先前的治疗。需要进一步研究， 确定GLP-1激活β细胞的机制 特定的基因，它对治疗胰腺炎有影响， 1型糖尿病也是。使用导管细胞系，AR 42 J细胞，我们有 表明细胞在处理后可以产生胰岛素 与GLP-1结合，它们对葡萄糖有反应。我们有 研究了参与GLP-1诱导的细胞内信号 AR 42 J细胞的分化，并发现它依赖于 MAP激酶通路的持续激活。我们计划做 在初级导管细胞系中进行研究，以确定是否存在相同的途径， 涉案

Aging is associated with an increased incidence of type 2 diabetes mellitus. On looking at the characteristics of the age-related decline in insulin secretion that occurs with aging, it appears that the abnormality in insulin secretion from beta cells of the pancreas that occurs in diabetes is an exaggeration of normal aging processes, coupled with increasing demand for insulin release in the setting of insulin resistance. Of great interest is the new information that these changes can be reversed. We treated young (3 months) and old (23 months) Wistar rats with an infusion of human recombinant GLP-1 (1.5 pmol per kg body weight per minute), a naturally-occurring gut peptide, using an ALZET osmotic pump (1003D) implanted subcutaneously in the neck for 5 days. Insulin mRNA was increased 3 fold in the GLP-1 infused animals. Even the old rats which have a lower amount of mRNA (50% lower) for insulin than young rats had a 3 fold increase in insulin mRNA. The abnormality in insulin secretion with aging was also normalized by this treatment. Of great interest is the fact that there is an increase in beta cell mass after chronic treatment with GLP-1. GLP-1 causes stem cells to proliferate which then differentiate into insulin-producing cells. This occurs in stem cells in the acinar and ductal tissue. This phenomenon has not been shown with any previous treatment. It will require further study to determine the mechanism by which GLP-1 activates beta cell specific genes and it has implications for treating pancreatitis and type 1 diabetes, also. Using a ductal cell line, AR42J cells, we have shown that the cells can become insulin- producing when treated with GLP-1, and they become responsive to glucose. We have investigated the intracellular signals involved in the GLP-1 induced differentiation of AR42J cells and found that it is dependent on the continuous activation of the MAP kinase pathway. We plan to do studies in primary duct cell lines to see if the same pathways are involved.