Bone Morphogenic Proteins as Novel Regulators of Beta Cell Growth

骨形态发生蛋白作为β细胞生长的新型调节剂

• 批准号: 8109183
• 负责人: JAKE ALDEN KUSHNER
• 金额: $ 30.68万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8109183
• 关键词: Acute; Adult; Affinity; BMP2 gene; BMP4; Beta Cell; Biological Preservation; Cell Proliferation; Cell physiology; Cells; Clinical; Data; Development; Diabetes Mellitus; Ductal Epithelium; Embryo; Embryonic Development; FDA approved; Financial compensation; Fracture; Gene Deletion; Gene Targeting; Goals; Growth; Growth and Development function; Healed; Health; In Vitro; Insulin-Dependent Diabetes Mellitus; Knock-out; Knockout Mice; Laboratories; Lead; Life; Ligand Binding; Ligands; Measurement; Mediating; Morphogenesis; Mus; Natural regeneration; Non-Insulin-Dependent Diabetes Mellitus; Pancreas; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Publishing; Relative (related person); Research; Role; Signal Pathway; Signal Transduction; Speed; Stimulation of Cell Proliferation; Stimulus; Techniques; Technology; Testing; Tissues; Translating; Transplantation; Work; autocrine; base; bone morphogenic protein; cell growth; diabetes mellitus therapy; embryo tissue; exenatide; fundamental research; glucagon-like peptide 1; healing; improved; in vivo; insulin secretion; islet; novel; novel strategies; parathyroid hormone-related protein; procollagen C-endopeptidase; receptor; research study; type I and type II diabetes

DESCRIPTION (provided by applicant): Inadequate ¿-cell mass is common to both type 1 and type 2 diabetes. Our long-term research goal is to understand the signals that influence ¿-cell growth, as a step towards regeneration of ¿-cell mass in diabetes patients. Surprisingly little is known about how ¿-cell growth is regulated, and few mitogenic signals have been demonstrated to influence ¿-cell mass. Bone Morphogenic Proteins (BMPs) are attractive candidate mitogenic signals in adult ¿-cells because of their roles in many embryonic tissues. There is no published evidence that BMPs influence adult ¿-cell growth. But, a large number of in vitro studies indicate that BMPs influence embryonic ¿-cell development. We will use inducible tissue specific gene deletion in mice to test the hypothesis that BMP signals regulate adult ¿-cell growth. The rationale for our studies is strengthened by our preliminary studies: Systemic BMP4 treatment stimulates ¿-cell proliferation in vivo, and acute Bmpr1a gene deletion severely reduces adult ¿-cell proliferation. Hence, the following Specific Aims: 1. Test the hypothesis that Bmpr1a signals regulate adult ¿-cell growth. 2. Test the hypothesis that Bmpr1b signals also regulate ¿-cell growth. 3. Test the hypothesis that autocrine BMP4 signals regulate adult ¿-cell growth. To carry out our studies we will employ techniques that are fully implemented in our laboratory, supported by substantial preliminary data. Thus, we anticipate that our studies could establish BMPs as a major mitogenic signaling pathway in ¿-cells. Importantly, an FDA approved BMP2 drug is already in routine clinical use to speed healing of bone fractures. These studies could ultimately lead to novel BMP based therapies for diabetes patients. PUBLIC HEALTH RELEVANCE: Improved understanding of beta-cell growth is an important diabetes research goal that could benefit diabetes patients, allowing preservation of insulin secretion in patients with type 2 diabetes, or expansion of islets for transplant into patients with type 1 diabetes. Here, we propose studies to genetically interrogate the role of the Bone Morphogenic Protein (BMP) signaling pathway in beta-cell growth, a novel strategy that could lead to the development of new therapies for diabetes.

描述（由申请人提供）：1型和2型糖尿病的常见症状是细胞质量不足。我们的长期研究目标是了解影响细胞生长的信号，作为糖尿病患者细胞群再生的一步。令人惊讶的是，人们对如何做到这一点知之甚少