GLUCOSE HOMEOSTASIS IN THE SURGICALLY ALTERED PANCREAS
手术改变的胰腺中的葡萄糖稳态
基本信息
- 批准号:2140983
- 负责人:
- 金额:$ 28.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1988
- 资助国家:美国
- 起止时间:1988-01-01 至 1998-12-13
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Surgical alterations of the pancreas have been used as treatment for
various disease processes. However, understanding of how anatomic
alterations of the pancreas can change postoperative regulation of
carbohydrate metabolism is unclear. Recently, pancreas transplantation has
been employed for Type I diabetes, yet very little understanding of post-
transplant insulin secretion exists. This application seeks continuation
of our efforts using three surgical models which are relevant to
understanding postoperative changes in glucose homeostasis and insulin
secretion. Distinct changes in insulin secretion appear to result because
of one of three anatomic alterations relevant to transplantation: 1.
reduction of beta cell mass, 2. systemic release of insulin in pancreatic
venous effluent, and 3. denervation (autotransplantation). Our canine
surgical models have been evaluated using intravenous (IVGTT) and oral
(OGTT) glucose challenge. Studies using euglycemic hyperinsulinemic and
hyperglycemic clamps have been performed. Our preliminary findings have
suggested that alteration in disposal of glucose exists over a varying
range of endogenous insulin levels. Systemic drainage of the pancreas
restores "normal" levels of insulin in the periphery, yet alterations in
peripheral glucose levels persist. Clamp studies suggest that sensitivity
to endogenous insulin is decreased. Studies to evaluate peripheral
sensitivity to exogenously infused insulin and hepatic glucose output have
not explained why these alterations exist. Additional studies have
suggested that factors other than insulin levels (insulin-independent
glucose disposal) and, possibly, the deficiency of an enteric hormone, GIP
(glucose-dependent insulinotropic polypeptide), or pancreatic polypeptide
(PP) may explain our findings. We propose to continue our efforts in three
areas. First, we wish to continue evaluating insulin response to glucose
challenge and examine more thoroughly enteric hormone deficiencies. Second,
we propose to evaluate the pulsatile pattern of insulin release, and
whether changes in normal secretory patterns by surgical interventions
would explain altered peripheral glucose levels. Third, we propose studies
to evaluate the immunosuppressive agent, cyclosporine, and its effect on
the surgical alterations relevant to pancreas transplantation using our
autotransplant model. These studies will allow basic observations about
physiologic glucoregulation of insulin release. The studies on pulsatile
release of insulin and cyclosporine effects offer unique opportunities to
evaluate postsurgical (transplant) effects on glucose homeostasis.
胰腺的手术改变已被用作治疗
各种疾病过程。然而,了解解剖学如何
胰腺的改变可以改变术后对
碳水化合物代谢尚不清楚。最近,胰腺移植已经
糖尿病患者,但对糖尿病后
存在移植胰岛素分泌。本申请寻求继续
我们使用三种手术模型,
了解术后葡萄糖稳态和胰岛素的变化
分泌物胰岛素分泌的明显变化似乎是由于
与移植相关的三种解剖学改变之一:1.
β细胞质量的减少,2.胰腺中胰岛素系统性释放
静脉流出物,和3.去神经(自体移植)。我们的狗
已经使用静脉内(IVGTT)和口服(oral
(OGTT)葡萄糖激发。使用正常血糖高胰岛素血症和
已经进行了高血糖钳夹。我们的初步发现
这表明,改变处置葡萄糖存在于一个不同的
内源性胰岛素水平的范围。胰腺系统引流
恢复“正常”水平的胰岛素在周边,但改变,
外周血糖水平持续存在。钳研究表明,敏感性
内源性胰岛素的水平降低。评价外周血管的研究
对外源性输注胰岛素的敏感性和肝葡萄糖输出量
没有解释为什么这些变化存在。另外的研究已经
提示胰岛素水平以外的因素(胰岛素非依赖性
葡萄糖处置),并可能,缺乏肠道激素,GIP
(葡萄糖依赖性促胰岛素多肽)或胰多肽
(PP)也许能解释我们的发现我们建议在三个方面继续努力,
地区首先,我们希望继续评估胰岛素对葡萄糖的反应
挑战和检查更彻底的肠道激素缺乏症。第二、
我们建议评估胰岛素释放的脉动模式,
手术干预是否改变了正常的分泌模式
可以解释外周血糖水平的改变第三,我们建议研究
评价免疫抑制剂环孢霉素及其对
使用我们的胰腺移植相关的手术改变
自体移植模型这些研究将允许基本的观察,
胰岛素释放的生理性葡萄糖调节。脉动流的研究
释放胰岛素和环孢霉素的作用提供了独特的机会,
评估术后(移植)对葡萄糖稳态的影响。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hyperinsulinemia after pancreatic transplantation. Prediction by a novel computer model and in vivo verification.
胰腺移植后出现高胰岛素血症。
- DOI:10.1097/00000658-199310000-00004
- 发表时间:1993
- 期刊:
- 影响因子:9
- 作者:Earnhardt,RC;Kindler,DD;Weaver,AM;Cornett,G;Elahi,D;Veldhuis,JD;Hanks,JB
- 通讯作者:Hanks,JB
Pancreas transplantation. An initial experience with systemic and portal drainage of pancreatic allografts.
- DOI:10.1097/00000658-199206000-00005
- 发表时间:1992-06
- 期刊:
- 影响因子:9
- 作者:L. Rosenlof;R. C. Earnhardt;T. L. Pruett;William C. Stevenson;Mary T. Douglas;G. Cornett;J. Hanks
- 通讯作者:L. Rosenlof;R. C. Earnhardt;T. L. Pruett;William C. Stevenson;Mary T. Douglas;G. Cornett;J. Hanks
Pathophysiology of hyperinsulinemia following pancreas transplantation: altered pulsatile versus Basal insulin secretion and the role of specific transplant anatomy in dogs.
胰腺移植后高胰岛素血症的病理生理学:脉动胰岛素分泌与基础胰岛素分泌的改变以及狗特定移植解剖结构的作用。
- DOI:10.1097/01.sla.0000029820.17138.d1
- 发表时间:2002
- 期刊:
- 影响因子:0
- 作者:Earnhardt,RichardC;Veldhuis,JohannesD;Cornett,Greg;Hanks,JohnB
- 通讯作者:Hanks,JohnB
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JOHN B HANKS其他文献
JOHN B HANKS的其他文献
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{{ truncateString('JOHN B HANKS', 18)}}的其他基金
METABOLIC ALTERATIONS AFTER PANCREAS TRANSPLANTATION
胰腺移植后的代谢变化
- 批准号:
6578960 - 财政年份:2002
- 资助金额:
$ 28.33万 - 项目类别:
METABOLIC ALTERATIONS AFTER PANCREAS TRANSPLANTATION
胰腺移植后的代谢变化
- 批准号:
6477487 - 财政年份:2001
- 资助金额:
$ 28.33万 - 项目类别:
METABOLIC ALTERATIONS AFTER PANCREAS TRANSPLANTATION
胰腺移植后的代谢变化
- 批准号:
6307510 - 财政年份:1999
- 资助金额:
$ 28.33万 - 项目类别:
METABOLIC ALTERATIONS AFTER PANCREAS TRANSPLANTATION
胰腺移植后的代谢变化
- 批准号:
6118249 - 财政年份:1998
- 资助金额:
$ 28.33万 - 项目类别:
REGULATION OF GLUCOSE HOMEOSTASIS IN FAMILIAL TYPE 2 DIABETES
家族性 2 型糖尿病中葡萄糖稳态的调节
- 批准号:
6265244 - 财政年份:1998
- 资助金额:
$ 28.33万 - 项目类别:
METABOLIC ALTERATIONS AFTER PANCREAS TRANSPLANTATION
胰腺移植后的代谢变化
- 批准号:
6279444 - 财政年份:1997
- 资助金额:
$ 28.33万 - 项目类别:
GLUCOSE HOMEOSTASIS IN THE SURGICALLY ALTERED PANCREAS
手术改变的胰腺中的葡萄糖稳态
- 批准号:
3239405 - 财政年份:1988
- 资助金额:
$ 28.33万 - 项目类别:
GLUCOSE HOMEOSTASIS IN THE SURGICALLY ALTERED PANCREAS
手术改变的胰腺中的葡萄糖稳态
- 批准号:
3239406 - 财政年份:1988
- 资助金额:
$ 28.33万 - 项目类别:
GLUCOSE HOMEOSTASIS AND THE SURGICALLY ALTERED PANCREAS
葡萄糖稳态和手术改变的胰腺
- 批准号:
3463239 - 财政年份:1988
- 资助金额:
$ 28.33万 - 项目类别:
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